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Azizoglu, A;Stelling, J
10.1042/BST20190295
null
1ST FLR, 10 QUEEN STREET PLACE, LONDON, ENGLAND
3034bk443e3q612p1s442q316z3m202t642527
Controlling cell-to-cell variability with synthetic gene circuits
Swiss Fed Inst Technol
null
Stelling, J (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland.
null
Azizoglu, Asli;Stelling, Jorg
Biochemistry & Molecular Biology
NCCR Molecular Systems Engineering - Swiss National Science Foundation
WOS
Stelling, J
Swiss Fed Inst Technol, Basel, Switzerland
47
cell-to-cell;circuits;controlling;gene;synthetic;variability;with
1
Azizoglu, Asli
PORTLAND PRESS LTD
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland;Swiss Fed Inst Technol, SIB Swiss Inst Bioinformat, CH-4058 Basel, Switzerland
Review
Swiss Fed Inst Technol
LONDON
null
null
Swiss Fed Inst Technol
NCCR Molecular Systems Engineering - Swiss National Science Foundation
Stelling, J (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland.
1804
Azizoglu, Asli;Stelling, Jorg
12
2
509,882,600,018
NCCR Molecular Systems Engineering - Swiss National Science Foundation
Switzerland
BIOCHEMICAL SOCIETY TRANSACTIONS
Switzerland
null
null
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland
0300-5127
Azizoglu, A;Stelling, J
DEC
joerg.stelling@bsse.ethz.ch
controlling cell-to-cell variability;synthetic gene circuits
2
J
Biochemistry & Molecular Biology
BIOLOGICAL NOISE;BIOLOGY;broad synthetic toolset;cell-to-cell variability;closed-loop;combination;components;control;controlling cell-to-cell variability;DEGRADATION;DESIGN;designing synthetic gene;drawing;engineering;exploration;expression;extensions;gene expression;help understanding natural functions;HETEROGENEITY;independent regulation;individual genes;instrumental;intrinsic noise;intrinsic stochasticity;major conceptual advances will;mean expression;natural systems;networks;new synthetic functions;new theory;noise control;noise reduction;noise shaping;origins;perspective;presents challenges;reducing noise;REVEALS;robust operation;single genes;STOCHASTICITY;synthetic biology approaches;synthetic feedback circuits;synthetic gene circuits;systematic considerations;traditional engineering concepts;TRANSCRIPTION;translation mechanisms;uncovering mechanisms underlying variability;variability
Azizoglu, A
BIOLOGICAL NOISE;DEGRADATION;DESIGN;EXPRESSION;HETEROGENEITY;REVEALS;STOCHASTICITY
1795
[Azizoglu, Asli; Stelling, Jorg] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland. [Azizoglu, Asli; Stelling, Jorg] Swiss Fed Inst Technol, SIB Swiss Inst Bioinformat, CH-4058 Basel, Switzerland.
We acknowledge financial support by the NCCR Molecular Systems Engineering funded by the Swiss National Science Foundation.
biology;broad synthetic toolset;cell-to-cell variability;closed-loop;combination;components;control;designing synthetic gene;drawing;engineering;exploration;extensions;gene expression;help understanding natural functions;independent regulation;individual genes;instrumental;intrinsic noise;intrinsic stochasticity;major conceptual advances will;mean expression;natural systems;networks;new synthetic functions;new theory;noise control;noise reduction;noise shaping;origins;perspective;presents challenges;reducing noise;robust operation;single genes;synthetic biology approaches;synthetic feedback circuits;systematic considerations;traditional engineering concepts;transcription;translation mechanisms;uncovering mechanisms underlying variability;variability
10.1016/j.arcontrol.2018.04.007;10.1016/j.bpj.2010.01.018;10.1016/j.cell.2008.09.050;10.1016/j.cell.2011.01.030;10.1016/j.cell.2014.02.039;10.1016/j.celrep.2019.03.001;10.1016/j.cels.2015.10.011;10.1016/j.cels.2018.08.002;10.1016/j.jmb.2004.09.073;10.1016/j.jtbi.2016.02.004;10.1016/j.mib.2016.07.009;10.1016/j.plrev.2005.03.003;10.1016/j.synbio.2017.09.003;10.1016/j.tibtech.2019.03.016;10.1021/acssynbio.6b00014;10.1021/acssynbio.6b00189;10.1021/acssynbio.6b00251;10.1021/acssynbio.7b00087;10.1021/acssynbio.7b00122;10.1021/acssynbio.8b00029;10.1021/acssynbio.8b00279;10.1021/sb300116y;10.1038/35002125;10.1038/35014651;10.1038/nature01546;10.1038/nature03998;10.1038/nature04785;10.1038/nature14244;10.1038/nature19841;10.1038/ncomms2471;10.1038/ncomms5761;10.1038/ng869;10.1038/nrmicro3239;10.1038/nrmicro3491;10.1038/s41467-018-02898-6;10.1038/s41467-018-05882-2;10.1038/s41467-018-07391-8;10.1038/s41467-019-10330-w;10.1038/s41467-019-11116-w;10.1038/s41576-019-0130-6;10.1038/s41586-019-1321-1;10.1039/c7me00032d;10.1042/BST20180500;10.1073/pnas.0408507102;10.1073/pnas.0608451104;10.1073/pnas.0809901106;10.1073/pnas.1416533112;10.1073/pnas.151588598;10.1073/pnas.162041399;10.1088/0034-4885/77/2/026601;10.1093/nar/gkq091;10.1093/nar/gku126;10.1093/nar/gkw1194;10.1098/rsif.2016.0380;10.1098/rsif.2018.0079;10.1101/492207];10.1101/gr.168773.113;10.1101/gr.178426.114;10.1101/gr.191635.115;10.1103/PhysRevE.95.062418;10.1109/MCS.2018.2810459;10.1111/1567-1364.12188;10.1126/science.1070919;10.1126/science.1098641;10.1126/science.1188308;10.1126/science.aac7341;10.1146/annurev-biophys-070816-033903;10.1186/s13036-017-0068-1;10.1371/journal.pbio.0020137;10.1371/journal.pcbi.1002140;10.1371/journal.pcbi.1002644;10.1371/journal.pcbi.1003161;10.1371/journal.pgen.1005206;10.7554/eLife.37272;[10.1016/j.cels.2016.01.004, 10.1016/j.cels.2016.02.010]
Swiss Fed Inst Technol
Azizoglu, A;Stelling, J
Azizoglu, A: Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland
null
null
75
null
Switzerland
Swiss Fed Inst Technol
Azizoglu, Asli
Green Accepted
BIOLOGICAL NOISE;DEGRADATION;DESIGN;EXPRESSION;HETEROGENEITY;REVEALS;STOCHASTICITY
Azizoglu, Asli; Stelling, Jorg;
null
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland;Swiss Fed Inst Technol, SIB Swiss Inst Bioinformat, CH-4058 Basel, Switzerland
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland;Swiss Fed Inst Technol, SIB Swiss Inst Bioinformat, CH-4058 Basel, Switzerland
1470-8752
null
null
2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
3
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland
Biochem. Soc. Trans.
Stelling, Jorg
PORTLAND PRESS LTD
,;a;achieve;adapted;advances;also;an;and;approaches;are;argue;biology;broad;but;by;cell-to-cell;challenges;circuits;closed-loop;combination;components;concepts;conceptual;considerations;control;conversely;could;designing;drawing;either;engineering;establish;established;example;exploration;expression;extending;extensions;feedback;field;focus;for;from;functions;gene;genes;has;help;how;in;includes;independent;individual;individually;instead;instrumental;intrinsic;its;major;mean;mechanisms;more;natural;networks;new;noise;of;on;operation;or;originating;origins;other;perform;perspective;presents;reducing;reduction;regulation;require;robust;robustly;shaping;single;stochasticity;synthetic;systematic;systems;than;that;the;theory;these;this;to;toolset;traditional;transcription;translation;uncovering;underlying;understanding;use;variability;we;will;with
Swiss Fed Inst Technol
Cell-to-cell variability originating, for example, from the intrinsic stochasticity of gene expression, presents challenges for designing synthetic gene circuits that perform robustly. Conversely, synthetic biology approaches are instrumental in uncovering mechanisms underlying variability in natural systems. With a focus on reducing noise in individual genes, the field has established a broad synthetic toolset. This includes noise control by engineering of transcription and translation mechanisms either individually, or in combination to achieve independent regulation of mean expression and its variability. Synthetic feedback circuits use these components to establish more robust operation in closed-loop, either by drawing on, but also by extending traditional engineering concepts. In this perspective, we argue that major conceptual advances will require new theory of control adapted to biology, extensions from single genes to networks, more systematic considerations of origins of variability other than intrinsic noise, and an exploration of how noise shaping, instead of noise reduction, could establish new synthetic functions or help understanding natural functions.
null
BIOLOGICAL NOISE;DEGRADATION;DESIGN;EXPRESSION;HETEROGENEITY;REVEALS;STOCHASTICITY
1
null
null
10
BIOLOGICAL NOISE;DEGRADATION;DESIGN;EXPRESSION;HETEROGENEITY;REVEALS;STOCHASTICITY
WOS:000509882600018
Swiss Fed Inst Technol, Basel, Switzerland
Switzerland
2,019
null
0000-0002-2600-1322
null
null
English
null
ACS SYNTH BIOL;ANNU REV BIOPHYS;ANNU REV CONTROL;BIOCHEM SOC T;BIOPHYS J;CELL;CELL REP;CELL SYST;CODON DEPENDENT NOIS;CURR OPIN MICROBIOL;ELIFE;FEMS YEAST RES;GENOME RES;IEEE CONTR SYST MAG;J Biol Eng;J MOL BIOL;J R SOC INTERFACE;J THEOR BIOL;MOL SYST DES ENG;NAT COMMUN;NAT GENET;NAT REV GENET;NAT REV MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS LIFE REV;PHYS REV E;PLOS BIOL;PLOS COMPUT BIOL;PLOS GENET;REP PROG PHYS;SCIENCE;SYN SYST BIOTECHNO;TRENDS BIOTECHNOL
Azizoglu, Asli;Stelling, Jorg
2024-03-11 ER
Ackermann, M;Aoki, S K;Aranda-Díaz, A;Balleza E.;Balázsi, G;Bandiera, L;Bashor, C J;Baudrimont, A;Becskei, A;Benzinger, D;Blake, W J;Boada, Y;Borkowski, O;Briat, C;Butzin, N C;Cameron, D E;Caveney, P M;Cole, J A;Colman-Lerner, A;Csárdi, G;Darlington, A P S;Del Vecchio, D;Duveau, F;Eling, N;Elowitz, M B;Engl, C;Engstrom, M D;Farquhar, K S;Fraser, H B;Guantes, R;Guimaraes, J C;Hansen, M M K;Hausser, J;Hooshangi, S;Hsiao, V;Karamasioti, E;Keren, L;Li, J;Marquez-Lago, T T;Meng, X;Metzger, B P H;Mundt, M;Murphy, K F;Nevozhay, D;Newman, J R S;Nielsen, A A K;Ozbudak, E M;Paulsson, J;Potvin-Trottier, L;Raj, A;Raser, J M;Redden, H;Salari, R;Schmiedel, J M;Sharon, E;Sherman, M S;Shu, C C;Swain, P S;Taniguchi, Y;Thattai, M;Tsimring, L S;Vandemoortele, G;Way, J C;Weisse, A Y;Yamanishi, M;Yang, S;Zopf, C J
KG3ZR
Basel, Switzerland
6
null
1
6
31,803,907
Azizoglu, Asli;Stelling, Jorg
BIOCHEM SOC T
Basel, Switzerland
Bagh, S;Bonnerjee, D;Mukhopadhyay, S
10.1021/acs.bioconjchem.9b00517
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
545c2z6o1z191w37c51z571d2v4p1d4o1723f
Design, Fabrication, and Device Chemistry of a 3-Input-3-Output Synthetic Genetic Combinatorial Logic Circuit with a 3-Input AND Gate in a Single Bacterial Cell
Homi Bhabha Natl Inst HBNI
null
Bagh, S (corresponding author), Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India.
null
Bagh, Sangram;Bonnerjee, Deepro;Mukhopadhyay, Sayak
Biochemical Research Methods;Biochemistry & Molecular Biology;Chemistry, Multidisciplinary;Chemistry, Organic
SINP intramural funding (Department of Atomic Energy, Govt. of India); SERB [CRG/201B/001394]; Ramanujan Felowship (DST), Govt. of India
WOS
Bagh, S
Homi Bhabha Natl Inst, Kolkata, India
30
,;3-Input;3-Input-3-Output;a;and;Bacterial;cell;chemistry;circuit;Combinatorial;design;device;Fabrication;gate;genetic;in;logic;of;Single;synthetic;with
1
Bagh, Sangram;Bonnerjee, Deepro;mukhopadhyay, sayak
AMER CHEMICAL SOC
Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India
Article
Homi Bhabha Natl Inst
WASHINGTON
null
null
Homi Bhabha Natl Inst
Ramanujan Felowship (DST), Govt. of India;SERB;SINP intramural funding (Department of Atomic Energy, Govt. of India)
Bagh, S (corresponding author), Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India.
3020
Bagh, Sangram;Bonnerjee, Deepro;Mukhopadhyay, Sayak
25
1
503,917,900,004
Ramanujan Felowship (DST), Govt. of India;SERB [CRG/201B/001394];SINP intramural funding (Department of Atomic Energy, Govt. of India)
India
BIOCONJUGATE CHEMISTRY
India
null
null
Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India
1043-1802
Bagh, S;Bonnerjee, D;Mukhopadhyay, S
DEC
sangram.bagh@saha.ac.in
3-Input;3-Input-3-Output Synthetic Genetic Combinatorial Logic Circuit;Device Chemistry;Fabrication;Gate;Single Bacterial Cell
3
J
Biochemistry & Molecular Biology;Chemistry
128 bp DNA scaffold;3-Input;3-input-3-output combinatorial logic circuit;3-input-3-output synthetic genetic circuit;3-Input-3-Output Synthetic Genetic Combinatorial Logic Circuit;advancement;BACTERIA;BINDING;BIOLOGY;biorobotics;circuit;circuit integrated three extracellular chemical signals;circuit minimization;complex systems level device chemistry;conjugated promoter engineering approach;cross-talk;Device Chemistry;digital-like;DNA;DNA nanotechnology;ESCHERICHIA-COLI;expression;Fabrication;few times;first;first 3-input-3-output logic function;first time;Gate;gate promoter reported;gates;higher number;hybrid promoter;in-cell molecular computation;increased physical size;inputs;integration;larger circuit;molecular computation;molecular interactions;multi-input-multi-output devices;multi-input-multi-output genetic logic devices;nature;new 2-input-2-output integrated circuit;noncascaded 1-gate-3-input synthetic;outputs;previous 3-input;principles;produced three different fluorescent proteins;protein-binding sites;realization;SCAFFOLD;SIGNIFICANCE;similar 3-input synthetic;Single Bacterial Cell;single piece;specificity;synthetic biology;truth table;two important characteristics
Bonnerjee, D
BINDING;BIOLOGY;ESCHERICHIA-COLI;EXPRESSION;PRINCIPLES;SPECIFICITY
3013
[Bonnerjee, Deepro; Mukhopadhyay, Sayak; Bagh, Sangram] Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India.
This work was financially supported by SINP intramural funding (Department of Atomic Energy, Govt. of India), SERB (CRG/201B/001394) and Ramanujan Felowship (DST), Govt. of India.
128 bp DNA scaffold;3-input;3-input-3-output combinatorial logic circuit;3-input-3-output synthetic genetic circuit;advancement;bacteria;biorobotics;circuit;circuit integrated three extracellular chemical signals;circuit minimization;complex systems level device chemistry;conjugated promoter engineering approach;cross-talk;digital-like;DNA;DNA nanotechnology;few times;first;first 3-input-3-output logic function;first time;gate;gate promoter reported;gates;higher number;hybrid promoter;in-cell molecular computation;increased physical size;inputs;integration;larger circuit;molecular computation;molecular interactions;multi-input-multi-output devices;multi-input-multi-output genetic logic devices;nature;new 2-input-2-output integrated circuit;noncascaded 1-gate-3-input synthetic;outputs;previous 3-input;produced three different fluorescent proteins;protein-binding sites;realization;scaffold;SIGNIFICANCE;similar 3-input synthetic;single bacterial cell;single piece;synthetic biology;truth table;two important characteristics
10.1002/biot.201300258;10.1007/s11047-018-9715-9;10.1016/j.bios.2012.08.011;10.1016/j.bpj.2009.08.050;10.1016/j.jmb.2015.10.004;10.1016/j.tibtech.2014.11.009;10.1016/S0092-8674(03)01077-8;10.1021/acs.nanolett.8b00526;10.1021/acssynbio.5b00124;10.1021/acssynbio.6b00057;10.1038/msb4100173;10.1038/nature11516;10.1038/nrm2698;10.1038/s41467-019-12021-y;10.1038/s41580-018-0024-z;10.1038/sj.gt.3302761;10.1073/pnas.0408507102;10.1073/pnas.1816591116;10.1093/nar/25.6.1203;10.1093/nar/gks973;10.1103/PhysRevE.77.021919;10.1103/PhysRevE.82.021911;10.1126/science.1232758;10.1128/JB.00427-09;10.1128/JB.186.3.631-637.2004;10.1186/s13036-019-0151-x;[10.1038/NMETH.2926, 10.1038/nmeth.2926];[10.1038/s41467-017-02473-5, 10.1038/s41467-018-05683-7]
Homi Bhabha Natl Inst
Bagh, S;Bonnerjee, D;Mukhopadhyay, S
Bonnerjee, D: Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India
mukhopadhyay, sayak
CRG/201B/001394
29
null
India
Homi Bhabha Natl Inst
Bonnerjee, Deepro
null
BINDING;BIOLOGY;ESCHERICHIA-COLI;EXPRESSION;PRINCIPLES;SPECIFICITY
Bonnerjee, Deepro; Mukhopadhyay, Sayak; Bagh, Sangram;
null
Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India
Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India
1520-4812
null
12
1997;2004;2005;2006;2007;2008;2009;2010;2012;2013;2014;2015;2016;2018;2019
8
Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Saha Inst Nucl Phys, Block A-F,Sect 1, Kolkata 700064, India
Bioconjugate Chem.
Bagh, Sangram
AMER CHEMICAL SOC
,;1-gate-3-input;128;2-input-2-output;3-input;3-input-3-output;a;adapting;advancement;also;and;approach;as;bacteria;bacterial;biology;biorobotics;both;bp;by;cell;characteristics;chemical;chemistry;circuit;combinatorial;complex;computation;conjugated;consists;created;cross-talk;demonstrated;design;device;devices;different;digital;digital-like;DNA;engineering;extracellular;few;first;fluorescent;following;for;function;gate;gates;genetic;has;here;higher;however;hybrid;important;in;in-cell;increased;inputs;integrated;integrating;integration;interactions;larger;level;limited;logic;mathematically;minimization;molecular;multi-input-multi-output;nanotechnology;nature;new;noncascaded;not;number;of;our;outputs;physical;piece;predictable;predictive;previous;produced;promoter;protein-binding;proteins;realization;reported;requires;scaffold;showed;signals;SIGNIFICANCE;similar;single;sites;size;smaller;such;synthetic;systems;table;than;that;the;this;three;time;times;truth;two;various;was;we;were;which;with;work;worked
Homi Bhabha Natl Inst
Advancement of in-cell molecular computation requires multi-input-multi-output genetic logic devices. However, increased physical size, a higher number of molecular interactions, cross-talk, and complex systems level device chemistry limited the realization of such multi-input-multi-output devices in a single bacterial cell. Here, by adapting a circuit minimization and conjugated promoter engineering approach, we created the first 3-input-3-output logic function in a single bacterial cell. The circuit integrated three extracellular chemical signals as inputs and produced three different fluorescent proteins as outputs following the truth table of the circuit. First, we created a noncascaded 1-gate-3-input synthetic genetic AND gate in bacteria. We showed that the 3-input AND gate was digital in nature and mathematically predictable, two important characteristics, which were not reported for previous 3-input AND gates in bacteria. Our design consists of a 128 bp DNA scaffold, which conjugated various protein-binding sites in a single piece of DNA and worked as a hybrid promoter. The scaffold was a few times smaller than the similar 3-input synthetic genetic AND gate promoter reported. Integrating this AND gate with a new 2-input-2-output integrated circuit, which was also digital-like and predictive, we created a 3-input-3-output combinatorial logic circuit. This work demonstrated the integration of a 3-input AND gate in a larger circuit and a 3-input-3-output synthetic genetic circuit, both for the first time. The work has significance in molecular computation, biorobotics, DNA nanotechnology, and synthetic biology.
HJI-3440-2023
BINDING;BIOLOGY;ESCHERICHIA-COLI;EXPRESSION;PRINCIPLES;SPECIFICITY
0
null
null
8
ESCHERICHIA-COLI;BINDING;BIOLOGY;EXPRESSION;PRINCIPLES;SPECIFICITY
WOS:000503917900004
Homi Bhabha Natl Inst, Kolkata, India
India
2,019
null
0000-0002-2172-6893;0000-0002-5736-0993;0000-0002-8565-0728
null
null
English
null
ACS SYNTH BIOL;BIOPHYS J;BIOSENS BIOELECTRON;BIOTECHNOL J;CELL;ELECT C COMPUTATIONA;GENE THER;J BACTERIOL;J Biol Eng;J MOL BIOL;MOL SYST BIOL;NANO LETT;NAT COMMUN;NAT COMPUT;NAT METHODS;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV E;SCIENCE;TRENDS BIOTECHNOL
Bagh, Sangram;Bonnerjee, Deepro;Mukhopadhyay, Sayak
2024-03-11 ER
Aleksandrov, A;Anderson, J C;Bagh, S;Bonnet, J;Bradley, R W;Brophy, J A N;Chen, Y;Del Vecchio, D;Fink, T L;Hirahara S.;Hooshangi, S;Iverson, S V;Lutz, R;Magaraci, M S;Mekler, V;Moon, T S;Müller, I E;Oehler, S;Pawson, T;Purnick, P E M;Roquet, N;Sarkar, K;Schwarz-Schilling, M;Swank, Z;Urbanowski, A L;Wang, B J;Xiang, Y Y;Xie, M Q
JX7NR
Kolkata, India
8
null
1
null
31,596,072
Bagh, Sangram;Bonnerjee, Deepro;Mukhopadhyay, Sayak
BIOCONJUGATE CHEM
Kolkata, India
Bovenberg, R A L;Büttel, Z;Driessen, A J M;Mózsik, L;Nygård, Y
10.1186/s12934-019-1253-3
203
CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
9601h2m696ay6g5g5a6t146m5p2c664a56b3s
Synthetic control devices for gene regulation in <i>Penicillium chrysogenum</i>
Univ Groningen
null
Nygård, Y (corresponding author), Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, Kemivagen 10, S-41296 Gothenburg, Sweden.;Nygård, Y (corresponding author), DSM Biotechnol Ctr, Alexander Fleminglaan 1, NL-2613 AX Delft, Netherlands.;Nygård, Y (corresponding author), Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands.
null
Bovenberg, Roel A L;Buttel, Zsofia;Driessen, Arnold J M;Mozsik, Laszlo;Nygard, Yvonne
Biotechnology & Applied Microbiology
People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/, under REA [607332]; European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie [713482]
WOS
Nygård, Y
Chalmers Univ Technol, Gothenburg, Sweden;DSM Biotechnol Ctr, Delft, Netherlands;Univ Groningen, Groningen, Netherlands
18
<i>Penicillium;chrysogenum</i>;control;devices;for;gene;in;regulation;synthetic
2
Buttel, Zsofia;Mozsik, Laszlo;Nygård, Yvonne
BMC
Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, Kemivagen 10, S-41296 Gothenburg, Sweden;DSM Biotechnol Ctr, Alexander Fleminglaan 1, NL-2613 AX Delft, Netherlands;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands.; Nygård, Y (corresponding author), DSM Biotechnol Ctr, Alexander Fleminglaan 1, NL-2613 AX Delft, Netherlands.; Nygård, Y (corresponding author), Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, Kemivagen 10, S-41296 Gothenburg, Sweden;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Synthet Biol & Cell Engn, Nijenborgh 7, NL-9747 AG Groningen, Netherlands
Article
Chalmers Univ Technol;DSM Biotechnol Ctr;Univ Groningen
LONDON
null
null
Chalmers Univ Technol;DSM Biotechnol Ctr;Univ Groningen
European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie;People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/, under REA
Nygård, Y (corresponding author), Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands.; Nygård, Y (corresponding author), DSM Biotechnol Ctr, Alexander Fleminglaan 1, NL-2613 AX Delft, Netherlands.; Nygård, Y (corresponding author), Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, Kemivagen 10, S-41296 Gothenburg, Sweden.
null
Bovenberg, Roel A L;Buttel, Zsofia;Driessen, Arnold J M;Mozsik, Laszlo;Nygard, Yvonne
7
4
511,651,300,003
European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie [713482];People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/, under REA [607332]
Netherlands;Sweden
MICROBIAL CELL FACTORIES
Netherlands;Sweden
null
null
Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands
null
Bovenberg, R A L;Büttel, Z;Driessen, A J M;Mózsik, L;Nygård, Y
NOV 18
yvonne.nygard@chalmers.se
<i>Penicillium chrysogenum</i>;gene regulation;synthetic control devices
5
J
Biotechnology & Applied Microbiology
<i>Penicillium chrysogenum</i>;affinity;application;background;binds;characterization;CLUSTER;compounds;conclusions;conditions;control device;control devices;CORE PROMOTERS;devices function;DNA binding domain;excellent indications;expression;EXPRESSION SYSTEM;filamentous fungi;fluorescent reporters;GENE;gene cluster;gene regulation;genes;great advantage;highest expressed native genes;Hybrid transcription factor;level;main components;microbioreactors;model filamentous fungus;Neurospora crassa;ORGANIZATION;PARTS;penicillin;Penicillium chrysogenum;performing control devices;production;production strains;PROTEIN;Q-SYSTEM;QF DNA-binding domain;quinic acid gene cluster;quinic acid upstream activating sequence (QUAS) elements;relevant cell factory;results;Secondary metabolite production;secondary metabolites;STRAIN;synthetic control devices;synthetic expression devices;Synthetic expression system;Synthetic gene cluster;synthetic promoter;synthetic transcription factor;synthetic transcription factors;SYSTEM;TET-ON;three;transcription factor;upstream activating domain;upstream activating sequences;versatility;VP16 activation domain;well-characterized
Mózsik, L
CLUSTER;CORE PROMOTERS;EXPRESSION SYSTEM;Gene regulation;Hybrid transcription factor;ORGANIZATION;PARTS;Penicillium chrysogenum;PROTEIN;Q-SYSTEM;Secondary metabolite production;STRAIN;Synthetic expression system;Synthetic gene cluster;TET-ON
null
[Mozsik, Laszlo; Buttel, Zsofia; Driessen, Arnold J. M.; Nygard, Yvonne] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands. [Bovenberg, Roel A. L.; Nygard, Yvonne] DSM Biotechnol Ctr, Alexander Fleminglaan 1, NL-2613 AX Delft, Netherlands. [Bovenberg, Roel A. L.] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Synthet Biol & Cell Engn, Nijenborgh 7, NL-9747 AG Groningen, Netherlands. [Nygard, Yvonne] Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, Kemivagen 10, S-41296 Gothenburg, Sweden.
YN and ZB received funding the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/, under REA grant agreement [No 607332] (QuantFung) and LM received funding from the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement [No 713482] (ALERT).
affinity;application;background;binds;characterization;compounds;conclusions;conditions;control device;control devices;devices function;DNA binding domain;excellent indications;expression;filamentous fungi;fluorescent reporters;gene;gene cluster;genes;great advantage;highest expressed native genes;level;main components;microbioreactors;model filamentous fungus;Neurospora crassa;penicillin;Penicillium chrysogenum;performing control devices;production;production strains;QF DNA-binding domain;quinic acid gene cluster;quinic acid upstream activating sequence (QUAS) elements;relevant cell factory;results;secondary metabolites;synthetic control devices;synthetic expression devices;synthetic promoter;synthetic transcription factor;synthetic transcription factors;system;three;transcription factor;upstream activating domain;upstream activating sequences;versatility;VP16 activation domain;well-characterized
10.1002/bit.24552;10.1007/978-1-4939-6371-3_3;10.1007/978-1-4939-7795-6_12;10.1007/978-1-61779-501-5_1;10.1007/s002530051509;10.1007/s10142-009-0110-6;10.1007/s12223-010-0019-4;10.1016/0022-2836(85)90183-4;10.1016/0092-8674(84)90457-4;10.1016/j.cell.2010.02.025;10.1016/j.fgb.2006.05.006;10.1016/j.fgb.2015.11.003;10.1016/j.fgb.2015.12.003;10.1016/j.ydbio.2009.08.009;10.1016/j.ymeth.2013.06.012;10.1016/S0003-2697(03)00166-0;10.1016/S0953-7562(09)80945-3;10.1021/acschembio.8b00679;10.1021/acssynbio.6b00082;10.1021/acssynbio.6b00178;10.1021/sb4001245;10.1021/sb500296p;10.1021/sb500366v;10.1038/335563a0;10.1038/nature07667;10.1038/nbt.1498;10.1038/ncomms13010;10.1038/nprot.2013.143;10.1039/c3np70034h;10.1042/BJ20081257;10.1073/pnas.1419028112;10.1080/07388550091144177;10.1093/nar/gkt1402;10.1093/nar/gkw553;10.1093/nar/gky558;10.1128/AEM.01529-12;10.1128/AEM.01702-10;10.1128/AEM.01742-17;10.1128/AEM.02740-10;10.1128/AEM.71.2.672-678.2005;10.1128/MCB.11.11.5746;10.1128/MMBR.49.3.338-358.1985;10.1186/1471-2164-10-75;10.1186/1471-2180-5-1;10.1186/1475-2859-13-53;10.1186/1475-2859-8-31;10.1186/s12864-015-2154-4;10.1186/s12934-016-0586-4;10.1186/s12934-019-1112-2;10.1186/s40694-016-0024-8;10.1371/journal.pone.0148320;10.1534/genetics.110.119917;10.3109/10408410903489576;10.3389/fmicb.2015.00184;[10.1038/nmeth.1929, 10.1038/NMETH.1929];[10.1038/nmeth.3250, 10.1038/NMETH.3250]
Univ Groningen
Bovenberg, R A L;Büttel, Z;Driessen, A J M;Mózsik, L;Nygård, Y
Mózsik, L: Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands
Driessen, Arnold J.M.;Nygård, Yvonne
607332;713482
57
null
Netherlands
Chalmers Univ Technol;DSM Biotechnol Ctr;Univ Groningen
Mozsik, Laszlo
Green Published, gold, Green Submitted
CLUSTER;CORE PROMOTERS;EXPRESSION SYSTEM;ORGANIZATION;PARTS;PROTEIN;Q-SYSTEM;STRAIN;TET-ON
Mozsik, Laszlo; Buttel, Zsofia; Bovenberg, Roel A. L.; Driessen, Arnold J. M.; Nygard, Yvonne;
null
Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, Kemivagen 10, S-41296 Gothenburg, Sweden;DSM Biotechnol Ctr, Alexander Fleminglaan 1, NL-2613 AX Delft, Netherlands;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Synthet Biol & Cell Engn, Nijenborgh 7, NL-9747 AG Groningen, Netherlands
Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, Kemivagen 10, S-41296 Gothenburg, Sweden;DSM Biotechnol Ctr, Alexander Fleminglaan 1, NL-2613 AX Delft, Netherlands;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Synthet Biol & Cell Engn, Nijenborgh 7, NL-9747 AG Groningen, Netherlands
1475-2859
Gene regulation;Hybrid transcription factor;Penicillium chrysogenum;Secondary metabolite production;Synthetic expression system;Synthetic gene cluster
1
1984;1985;1988;1991;1992;1999;2000;2003;2005;2006;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
13
Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, Kemivagen 10, S-41296 Gothenburg, Sweden;DSM Biotechnol Ctr, Alexander Fleminglaan 1, NL-2613 AX Delft, Netherlands;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Mol Microbiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands
Microb. Cell. Fact.
Nygard, Yvonne
BMC
(QUAS);,;:;a;acid;activating;activation;advantage;affinity;an;and;anticipate;application;applied;background;be;binding;binds;by;can;cell;characterization;characterized;chrysogenum;cluster;components;compounds;conclusions;conditions;confirmed;containing;control;controlling;controls;crassa;demand;demonstrated;detectable;developed;device;devices;DNA;DNA-binding;domain;each;elements;excellent;expressed;expression;factor;factors;factory;filamentous;fluorescent;for;from;function;fungi;fungus;fused;gene;genes;give;great;hardly;highest;how;in;indications;individually;industrially;is;it;its;level;main;may;metabolites;microbioreactors;model;native;Neurospora;of;Orthogonal;other;penicillin;Penicillium;performing;production;promoter;proved;provided;QF;quinic;ranging;relevant;reporters;respect;resulted;results;robustly;secondary;sequence;sequences;similar;strains;synthetic;synthetically;system;that;the;their;these;this;three;to;transcription;tuned;under;upstream;versatility;VP16;was;we;well-characterized;were;where;which;widely;with
Chalmers Univ Technol;DSM Biotechnol Ctr;Univ Groningen
Background: Orthogonal, synthetic control devices were developed for Penicillium chrysogenum, a model filamentous fungus and industrially relevant cell factory. In the synthetic transcription factor, the QF DNA-binding domain of the transcription factor of the quinic acid gene cluster of Neurospora crassa is fused to the VP16 activation domain. This synthetic transcription factor controls the expression of genes under a synthetic promoter containing quinic acid upstream activating sequence (QUAS) elements, where it binds. A gene cluster may demand an expression tuned individually for each gene, which is a great advantage provided by this system. Results: The control devices were characterized with respect to three of their main components: expression of the synthetic transcription factors, upstream activating sequences, and the affinity of the DNA binding domain of the transcription factor to the upstream activating domain. This resulted in synthetic expression devices, with an expression ranging from hardly detectable to a level similar to that of highest expressed native genes. The versatility of the control device was demonstrated by fluorescent reporters and its application was confirmed by synthetically controlling the production of penicillin. Conclusions: The characterization of the control devices in microbioreactors, proved to give excellent indications for how the devices function in production strains and conditions. We anticipate that these well-characterized and robustly performing control devices can be widely applied for the production of secondary metabolites and other compounds in filamentous fungi.
AAV-4877-2020;D-1876-2012
CLUSTER;CORE PROMOTERS;EXPRESSION SYSTEM;ORGANIZATION;PARTS;PROTEIN;Q-SYSTEM;STRAINS;TET-ON
0
null
Gene regulation;Hybrid transcription factor;Penicillium chrysogenum;Secondary metabolite production;Synthetic expression system;Synthetic gene cluster
13
CLUSTER;CORE PROMOTER;EXPRESSION SYSTEM;Gene regulation;Hybrid transcription factor;ORGANIZATION;PARTS;PENICILLIUM-CHRYSOGENUM;PROTEIN;Q-SYSTEM;Secondary metabolite production;STRAINS;Synthetic expression system;Synthetic gene cluster;TET-ON
WOS:000511651300003
Chalmers Univ Technol, Gothenburg, Sweden;DSM Biotechnol Ctr, Delft, Netherlands;Univ Groningen, Groningen, Netherlands
Netherlands;Sweden
2,019
null
0000-0001-5211-3873;0000-0001-6117-0343;0000-0003-0138-7553
null
null
English
null
ACS CHEM BIOL;ACS SYNTH BIOL;ANAL BIOCHEM;APPL ENVIRON MICROB;APPL MICROBIOL BIOT;BIOCHEM J;BIOTECHNOL BIOENG;BMC GENOMICS;BMC MICROBIOL;CELL;CRIT REV BIOTECHNOL;CRIT REV MICROBIOL;DEV BIOL;FOLIA MICROBIOL;FRONT MICROBIOL;FUNCT INTEGR GENOMIC;Fungal Biol Biotechnol;FUNGAL GENET BIOL;GENETICS;J MOL BIOL;METHODS;METHODS MOL BIOL;MICROB CELL FACT;MICROBIOL REV;MOL CELL BIOL;MYCOL RES;NAT BIOTECHNOL;NAT COMMUN;NAT METHODS;NAT PROD REP;NAT PROTOC;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;US patent
Bovenberg, Roel A L;Buttel, Zsofia;Driessen, Arnold J M;Mozsik, Laszlo;Nygard, Yvonne
2024-03-11 ER
Blazeck, J;Bovenberg, R A L;Burger, G;Cai, P;Díez, B;Eidtmann, A;Ermak, G;Gibbs, P A;Giles, N H;Gorochowski, T E;Grau, M F;Gressler, M;Harris, D M;Juven-Gershon, T;Kakule, T B;Kalderon, D;Kaplan, N;Kensy, F;Kiel, J A K W;Kiesenhofer, D P;Koetsier, M J;Kovalchuk, A;Kunze, M;Lee, M E;Losson, R;Mcisaac, R S;Mclean, K J;Meyer Vera;Meyer, V;Nijland, J G;Ongley, S E;Pachlinger, R;Pfeiffer, B D;Pohl, C;Polli, F;Portela, R M C;Potter, C J;Rajkumar, A S;Ran, F A;Rantasalo, A;Riabinina, O;Ruiz, B;Sadowski, I;Salo, O V;Smidák, R;Sonderegger, C;Subedi, A;Van Den Berg, M A;Vogt, K;Wanka, F;Weber, S S;Wei, X;Zarnack, K
KI9BI
Delft, Netherlands.;Gothenburg, Sweden;Groningen, Netherlands.
14
null
3
null
31,739,777
Bovenberg, Roel A L;Buttel, Zsofia;Driessen, Arnold J M;Mozsik, Laszlo;Nygard, Yvonne
MICROB CELL FACT
Delft, Netherlands;Gothenburg, Sweden;Groningen, Netherlands
Chang, M W;Foo, J L;Ling, H;Xia, P F
10.1016/j.biotechadv.2019.04.015
107393
THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
1s1f5j644g1t1r6l6f3p382v6n6d2p5f5g6e315p
Synthetic genetic circuits for programmable biological functionalities
Natl Univ Singapore
null
Foo, JL; Chang, MW (corresponding author), Ctr Life Sci, 28 Med Dr,02-07, Singapore 117456, Singapore.
null
Chang, Matthew Wook;Foo, Jee Loon;Ling, Hua;Xia, Peng-Fei
Biotechnology & Applied Microbiology
Synthetic Biology Initiative of the National University of Singapore [DPRT/943/09/14]; Ministry of Education, Singapore [MOE/2014/T2/2/128]; Synthetic Biology RD Programme [SBP-P2, SBP-P7]; Industry Alignment Fund Industry Collaboration Project [ICP1600012]; Investigatorship (NRFI) of the National Research Foundation, Singapore [ARO/2019/74459LS]; U.S. Army [ARO/2019/74459LS]
WOS
Chang, M W;Foo, J L
Natl Univ Singapore, Singapore, Singapore
37
biological;circuits;for;functionalities;genetic;programmable;synthetic
1
Ling, Hua;Xia, Pengfei
PERGAMON-ELSEVIER SCIENCE LTD
MW (corresponding author), Ctr Life Sci, 28 Med Dr,02-07, Singapore 117456, Singapore;Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, 8 Med Dr, Singapore 117597, Singapore;Natl Univ Singapore, NUS Synthet Biol Clin & Technol Innovat SynCTI, 28 Med Dr, Singapore 117456, Singapore
Review
Ctr Life Sci
OXFORD
null
null
Natl Univ Singapore
Industry Alignment Fund Industry Collaboration Project;Investigatorship (NRFI) of the National Research Foundation, Singapore;Ministry of Education, Singapore;Synthetic Biology Initiative of the National University of Singapore;Synthetic Biology RD Programme;U.S. Army
Foo, JL; Chang, MW (corresponding author), Ctr Life Sci, 28 Med Dr,02-07, Singapore 117456, Singapore.
null
Chang, Matthew Wook;Foo, Jee Loon;Ling, Hua;Xia, Peng-Fei
181
2
484,647,000,023
Industry Alignment Fund Industry Collaboration Project [ICP1600012];Investigatorship (NRFI) of the National Research Foundation, Singapore [ARO/2019/74459LS];Ministry of Education, Singapore [MOE/2014/T2/2/128];Synthetic Biology Initiative of the National University of Singapore [DPRT/943/09/14];Synthetic Biology RD Programme [SBP-P2, SBP-P7];U.S. Army [ARO/2019/74459LS]
Singapore
BIOTECHNOLOGY ADVANCES
Singapore
null
null
Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, 8 Med Dr, Singapore 117597, Singapore
0734-9750
Chang, M W;Foo, J L;Ling, H;Xia, P F
NOV 1
bchcmw@nus.edu.sg;bchfjl@nus.edu.sg
programmable biological functionalities;synthetic genetic circuits
4
J
Biotechnology & Applied Microbiology
accomplishments;autonomous modulation;Bioengineering;biological containment methods;biological units;biotechnology;Boolean logic gates;building;capabilities;CARBON-DIOXIDE;challenges;circuit architecture;CIRCUITS;CLOSTRIDIUM-BEIJERINCKII;complex genetic machines;complex genetic networks;concepts;CRISPR-CAS SYSTEMS;DESIGN;diagnostics;different circuits;directed evolution;dynamic;DYNAMIC PATHWAY REGULATION;ENGINEERED BACTERIA;environment;expression;features;feedback loops;genetic circuit;Genetic circuits;genetic devices;genetic materials;guideline;LACTOCOCCUS-LACTIS;living organisms;metabolic networks;microorganisms;modularized building blocks;modularized genetic parts;networks;new chapter;novel applications;oscillators;principles;programmable biological functionalities;programmable decision-making;Programmable functionalities;rapid development;realistic applications;realization;recent advances;release;review gives new insights;STATE MACHINES;synthetic biology;synthetic genetic circuits;therapies;toggle switch;toggle switches;units;variety
Xia, P F
CARBON-DIOXIDE;CLOSTRIDIUM-BEIJERINCKII;CRISPR-CAS SYSTEMS;DESIGN;DYNAMIC PATHWAY REGULATION;ENGINEERED BACTERIA;EXPRESSION;Genetic circuits;Genetic devices;LACTOCOCCUS-LACTIS;Programmable functionalities;STATE MACHINES;toggle switch
null
[Xia, Peng-Fei; Ling, Hua; Foo, Jee Loon; Chang, Matthew Wook] Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, 8 Med Dr, Singapore 117597, Singapore. [Xia, Peng-Fei; Ling, Hua; Foo, Jee Loon; Chang, Matthew Wook] Natl Univ Singapore, NUS Synthet Biol Clin & Technol Innovat SynCTI, 28 Med Dr, Singapore 117456, Singapore.
This work was supported by the Synthetic Biology Initiative of the National University of Singapore (DPRT/943/09/14), the Ministry of Education, Singapore (MOE/2014/T2/2/128), the Synthetic Biology R&D Programme (SBP-P2, SBP-P7), the Industry Alignment Fund Industry Collaboration Project (ICP1600012) and Investigatorship (NRFI) of the National Research Foundation, Singapore, and the U.S. Army (ARO/2019/74459LS).
accomplishments;autonomous modulation;bioengineering;biological containment methods;biological units;biotechnology;Boolean logic gates;building;capabilities;challenges;circuit architecture;circuits;complex genetic machines;complex genetic networks;concepts;diagnostics;different circuits;directed evolution;dynamic;environment;features;feedback loops;genetic circuit;genetic circuits;genetic materials;guideline;living organisms;metabolic networks;microorganisms;modularized building blocks;modularized genetic parts;networks;new chapter;novel applications;oscillators;principles;programmable decision-making;programmable functionalities;rapid development;realistic applications;realization;recent advances;release;review gives new insights;synthetic biology;synthetic genetic circuits;therapies;toggle switches;units;variety
10.1002/biot.201300258;10.1002/biot.201600099;10.1002/biot.201700159;10.1002/biot.201700543;10.1002/bit.25722;10.1002/bit.25980;10.1002/bit.26020;10.1002/bit.26275;10.1002/bit.26279;10.1002/bit.26404;10.1007/s00018-018-2827-7;10.1007/s11047-018-9715-9;10.1016/j.bios.2012.08.011;10.1016/j.bios.2014.07.003;10.1016/j.biotechadv.2018.04.007;10.1016/j.biotechadv.2018.07.005;10.1016/j.cbpa.2013.10.003;10.1016/j.cbpa.2016.08.023;10.1016/j.cell.2009.12.029;10.1016/j.cell.2013.02.022;10.1016/j.cell.2016.05.003;10.1016/j.cels.2015.06.001;10.1016/j.cels.2016.07.012;10.1016/j.chembiol.2009.02.011;10.1016/j.copbio.2017.06.011;10.1016/j.copbio.2017.10.005;10.1016/j.copbio.2018.01.011;10.1016/j.drup.2016.06.002;10.1016/j.jmb.2015.10.004;10.1016/j.mib.2017.08.005;10.1016/j.mib.2017.12.011;10.1016/j.molcel.2011.08.023;10.1016/j.molcel.2016.06.006;10.1016/j.molcel.2017.10.033;10.1016/j.molcel.2018.01.003;10.1016/j.nbt.2014.12.009;10.1016/j.procbio.2017.02.013;10.1016/j.tibtech.2015.12.014;10.1016/j.tig.2005.05.008;10.1016/j.watres.2017.06.008;10.1016/j.ymben.2015.03.008;10.1016/j.ymben.2018.03.009;10.1016/j.ymben.2018.04.008;10.1016/j.ymben.2018.04.011;10.1016/j.ymben.2018.06.006;10.1016/S0092-8674(03)00346-5;10.1021/acssynbio.5b00264;10.1021/acssynbio.6b00044;10.1021/acssynbio.6b00060;10.1021/acssynbio.6b00167;10.1021/acssynbio.6b00201;10.1021/acssynbio.6b00257;10.1021/acssynbio.6b00374;10.1021/acssynbio.7b00163;10.1021/acssynbio.7b00203;10.1021/acssynbio.7b00322;10.1021/acssynbio.7b00328;10.1021/acssynbio.8b00213;10.1021/acssynbio.8b00488;10.1021/sb400077j;10.1021/sb4001799;10.1021/sb500090b;10.1038/35002131;10.1038/msb.2011.55;10.1038/msb.2013.58;10.1038/nature07389;10.1038/nature08187;10.1038/nature09565;10.1038/nature10213;10.1038/nature11516;10.1038/nature12148;10.1038/nature13314;10.1038/nature14121;10.1038/nature23017;10.1038/nature23271;10.1038/nbt.1586;10.1038/nbt.2510;10.1038/nbt.2689;10.1038/nbt.3471;10.1038/nbt.3796;10.1038/nbt.3805;10.1038/nbt.3879;10.1038/nbt740;10.1038/nbt840;10.1038/nbt986;10.1038/ncomms15028;10.1038/ncomms15336;10.1038/ncomms15459;10.1038/ncomms2404;10.1038/ncomms3580;10.1038/ncomms3595;10.1038/ncomms7989;10.1038/ncomms8832;10.1038/nprot.2014.089;10.1038/nrg3227;10.1038/nrm.2015.2;10.1038/nrmicro.2015.24;10.1038/nrmicro.2017.172;10.1038/nrmicro2730;10.1038/nrmicro3239;10.1038/s41467-017-00511-w;10.1038/s41467-017-01695-x;10.1038/s41467-018-04901-6;10.1038/s41467-018-05332-z;10.1038/s41467-018-05466-0;10.1038/s41580-018-0024-z;10.1038/s41589-018-0056-x;10.1038/s41589-018-0168-3;10.1038/s41598-018-21350-9;10.1039/c0cc05037g;10.1046/j.1365-2958.2003.03867.x;10.1073/pnas.1009747107;10.1073/pnas.1120788109;10.1073/pnas.120163297;10.1073/pnas.1202344109;10.1073/pnas.1321321111;10.1073/pnas.1406401111;10.1093/femsle/fny222;10.1093/nar/gkn991;10.1093/nar/gku1378;10.1093/nar/gku1388;10.1093/nar/gku593;10.1093/nar/gku971;10.1093/nar/gkw232;10.1093/nar/gkx1319;10.1093/nar/gky884;10.1101/gr.193433.115;10.1126/science.1100829;10.1126/science.1205527;10.1126/science.aac7341;10.1126/science.aad3317;10.1126/science.aad8559;10.1126/science.aao0958;10.1126/science.aap8992;10.1126/science.aat9249;10.1126/scitranslmed.aak9537;10.1128/mBio.00928-13;10.1146/annurev-genet-120215-034902;10.1146/annurev-micro-091014-104306;10.1186/s12915-015-0146-0;10.1186/s12934-016-0595-3;10.15252/msb.20156663;10.15252/msb.20188605;10.2337/db11-1019;10.2337/db13-1236;10.2337/db14-0635;10.3389/fmicb.2018.00154;10.3390/genes9070351;[10.1016/j.cophio.2018.01.002, 10.1016/j.copbio.2018.01.002];[10.1038/nchembio.1979, 10.1038/NCHEMBIO.1979];[10.1038/nchembio.2233, 10.1038/NCHEMBIO.2233];[10.1038/NCHEMBIO.919, 10.1038/nchembio.919];[10.1038/NMETH.1318, 10.1038/nmeth.1318];[10.1038/NMETH.2926, 10.1038/nmeth.2926];[10.1038/NNANO.2014.32, 10.1038/nnano.2014.32];[10.1039/c6ee01108j, 10.1039/C6EE01108J]
Natl Univ Singapore
Chang, M W;Foo, J L;Ling, H;Xia, P F
Xia, P F: Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, 8 Med Dr, Singapore 117597, Singapore
Xia, Pengfei
ARO/2019/74459LS;DPRT/943/09/14;ICP1600012;MOE/2014/T2/2/128;SBP-P2;SBP-P7
158
null
Singapore
Natl Univ Singapore
Xia, Peng-Fei
hybrid
CARBON-DIOXIDE;CLOSTRIDIUM-BEIJERINCKII;CRISPR-CAS SYSTEMS;DESIGN;DYNAMIC PATHWAY REGULATION;ENGINEERED BACTERIA;EXPRESSION;LACTOCOCCUS-LACTIS;STATE MACHINES;TOGGLE SWITCH
Xia, Peng-Fei; Ling, Hua; Foo, Jee Loon; Chang, Matthew Wook;
null
Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, 8 Med Dr, Singapore 117597, Singapore;Natl Univ Singapore, NUS Synthet Biol Clin & Technol Innovat SynCTI, 28 Med Dr, Singapore 117456, Singapore
Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, 8 Med Dr, Singapore 117597, Singapore;Natl Univ Singapore, NUS Synthet Biol Clin & Technol Innovat SynCTI, 28 Med Dr, Singapore 117456, Singapore
1873-1899
Genetic circuits;genetic device;Programmable functionalities
6
1999;2000;2002;2003;2004;2005;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
66
Ctr Life Sci, 28 Med Dr,02-07, Singapore 117456, Singapore
Biotechnol. Adv.
Chang, Matthew Wook
PERGAMON-ELSEVIER SCIENCE LTD
,;a;accomplishments;advances;and;applications;architecture;are;as;aspects;autonomous;be;been;bioengineering;biological;biology;biotechnology;blocks;Boolean;building;capabilities;challenges;chapter;circuit;circuits;complex;concepts;consequently;construct;containment;could;created;decision-making;design;development;diagnostics;different;directed;discussed;distinct;due;dynamic;employed;employing;engineered;environment;envision;evolution;evolve;facilitate;features;feedback;for;from;functionalities;furthermore;gates;genetic;gives;guideline;have;herein;highlighted;identified;impart;implementation;in;including;initiated;insights;interact;into;led;living;logic;loops;machines;materials;metabolic;methods;microorganisms;modularized;modulation;networks;new;novel;of;offers;on;organisms;oscillators;outline;parts;prevent;principles;programmable;rapid;realistic;realization;recent;release;remote;review;such;switches;synthetic;targeted;that;the;therapies;these;they;this;to;toggle;transforming;units;variety;various;we;well;with
Ctr Life Sci
Living organisms evolve complex genetic networks to interact with the environment. Due to the rapid development of synthetic biology, various modularized genetic parts and units have been identified from these networks. They have been employed to construct synthetic genetic circuits, including toggle switches, oscillators, feedback loops and Boolean logic gates. Building on these circuits, complex genetic machines with capabilities in programmable decision-making could be created. Consequently, these accomplishments have led to novel applications, such as dynamic and autonomous modulation of metabolic networks, directed evolution of biological units, remote and targeted diagnostics and therapies, as well as biological containment methods to prevent release of engineered microorganisms and genetic materials. Herein, we outline the principles in genetic circuit design that have initiated a new chapter in transforming concepts to realistic applications. The features of modularized building blocks and circuit architecture that facilitate realization of circuits for a variety of novel applications are discussed. Furthermore, recent advances and challenges in employing genetic circuits to impart microorganisms with distinct and programmable functionalities are highlighted. We envision that this review gives new insights into the design of synthetic genetic circuits and offers a guideline for the implementation of different circuits in various aspects of biotechnology and bioengineering.
Q-3174-2019
CARBON-DIOXIDE;CLOSTRIDIUM-BEIJERINCKII;CRISPR-CAS SYSTEMS;DESIGN;DYNAMIC PATHWAY REGULATION;ENGINEERED BACTERIA;EXPRESSION;LACTOCOCCUS-LACTIS;STATE MACHINES;TOGGLE SWITCH
8
null
Genetic circuits;Genetic devices;Programmable functionalities
12
CARBON-DIOXIDE;CLOSTRIDIUM-BEIJERINCKII;CRISPR-CAS SYSTEMS;DESIGN;DYNAMIC PATHWAY REGULATION;ENGINEERED BACTERIA;EXPRESSION;Genetic circuits;genetic device;LACTOCOCCUS-LACTIS;Programmable functionalities;STATE MACHINES;toggle switch
WOS:000484647000023
Natl Univ Singapore, Singapore, Singapore
Singapore
2,019
null
0000-0001-5881-9834;0000-0002-0680-6422
null
null
English
null
ACS SYNTH BIOL;ANNU REV GENET;ANNU REV MICROBIOL;APPL ENVIRON MICROB;BIOSENS BIOELECTRON;BIOTECHNOL ADV;BIOTECHNOL BIOENG;BIOTECHNOL J;BMC BIOL;CELL;CELL MOL LIFE SCI;CELL SYST;CHEM BIOL;CHEM COMMUN;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;CURR OPIN MICROBIOL;DIABETES;DRUG RESIST UPDATE;ENERG ENVIRON SCI;FEMS MICROBIOL LETT;FRONT MICROBIOL;GENES-BASEL;GENOME RES;J MOL BIOL;MBIO;METAB ENG;MICROB CELL FACT;MOL CELL;MOL MICROBIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT COMPUT;NAT METHODS;NAT NANOTECHNOL;NAT PROTOC;NAT REV GENET;NAT REV MICROBIOL;NAT REV MOL CELL BIO;NATURE;NEW BIOTECHNOL;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PROCESS BIOCHEM;SCI REP-UK;SCI TRANSL MED;SCIENCE;TRENDS BIOTECHNOL;TRENDS GENET;WATER RES
Chang, Matthew Wook;Foo, Jee Loon;Ling, Hua;Xia, Peng-Fei
2024-03-11 ER
Atkinson, M R;Atsumi, S;Bikard, D;Bonnet, J;Borrero, J;Bothfeld, W;Bradley, R W;Brophy, J A N;Caliando, B J;Callura, J M;Cameron, D E;Cao, Y X;Chan, C T Y;Chen, B B;Chou, H H;Dahl, R H;Daniel, R;Datsenko, K A;Deaner, M;Dominguez, A A;Dong, C;Dou, J;Duan, F F;Farzadfard, F;Foo, J L;Gallagher, R R;Gander, M W;Gardner, T S;Gibson, D G;Gomaa, A A;Gottesman, S;Green, A A;Groher, F;Gupta, A;Harms, A;Hayden, E C;Heaver, S L;Higashikuni, Y;Higo, A;Holkenbrink, C;Holtz, W J;Hoynes-O'Connor, A;Hsiao, V;Huang, C H;Huang, H;Hwang, I Y;Immethun, C M;Isaacs, F J;Jacobsen, C N;Jang, S;Joseph, R C;Jusiak, B;Kau, A L;Kim, S J;Kortmann, J;Kotula, J W;Kushwaha, M;Lee, H L;Lee, J W;Lee, Y J;Li, Z J;Lian, J Z;Liang, J C;Lim, H G;Liu, M M;Liu, Q J;Lo, T M;Luo, M L;Maier, J A H;Malyshev, D A;Mandal, M;Mandell, D J;Metzner, M;Meyer, A J;Mimee, M;Moon, T S;Moser, F;Mougiakos, L;Mutalik, V K;Nielsen, A A K;Oishi, K;Oliver, N J;Peters, J M;Pham, H L;Piraner, D I;Pontrelli, S;Qi, L S;Rebello, S;Rhodius, V A;Richter, H;Riglar, D T;Robert, S;Roquet, N;Rossmanith, J;Saeidi, N;Sakimoto, K K;Schwartz, C;Seok, J Y;Shao, Z Y;Shapiro, M G;Shen, Y;Sherwood, A V;Sheth, R U;Shipman, S L;Siuti, P;Slusarczyk, A L;Smanski, M J;Steidler, L;Stirling, F;Stricker, J;Sun, T;Szymanski, E;Tamsir, A;Tang, W X;Taton, A;Temme, K;Tolhurst, G;Wang, B J;Wang, H H;Wang, M M;Wang, Y;Webster, D P;Wei, N;Weinberg, B H;Williams, T C;Win, M N;Wong, A;Wong, A S L;Woolston, B M;Xia, P F;Xiang, Y Y;Xie, M Q;Xie, Z;Xu, P;Yang, J;Yang, Y P;Yao, L;Yin, H;Yu, B J;Zhang, S Y;Zheng, J H
IW0JA
Singapore, Singapore
78
null
1
null
31,051,208
Chang, Matthew Wook;Foo, Jee Loon;Ling, Hua;Xia, Peng-Fei
BIOTECHNOL ADV
Singapore, Singapore
Dong, F;Gu, D C;Liao, Y Y;Wang, X W;Yang, Z Y;Zeng, L T
10.1016/j.postharvbio.2019.110974
110974
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
2y4k4tm3l513w4x4k6w2r2c3c2i631b6d6g5q6k
Formation of and changes in phytohormone levels in response to stress during the manufacturing process of oolong tea (<i>Camellia sinensis</i>)
Chinese Acad Sci
null
Yang, ZY (corresponding author), Chinese Acad Sci, Guangdong Prov Key Lab Appl Bot, South China Bot Garden, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China.;Yang, ZY (corresponding author), Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China.
null
Dong, Fang;Gu, Dachuan;Liao, Yinyin;Wang, Xuewen;Yang, Ziyin;Zeng, Lanting
Agronomy;Food Science & Technology;Horticulture
National Natural Science Foundation of China [31870684]; National Key Research and Development Program of China [2018YFD1000601]; China Postdoctoral Science Foundation [2018M640837]; Guangdong Natural Science Foundation for Distinguished Young Scholar [2016A030306039]
WOS
Yang, Z Y
Chinese Acad Sci, Guangdong, Peoples R China;Guangdong Food & Drug Vocat Coll, Guangdong, Peoples R China;Univ Chinese Acad Sci, Beijing, Peoples R China
157
(<i>Camellia;and;changes;during;formation;in;levels;manufacturing;of;oolong;phytohormone;process;response;sinensis</i>);stress;tea;the;to
1
null
ELSEVIER
Chinese Acad Sci, Ctr Econ Bot, Core Bot Gardens, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Chinese Acad Sci, Guangdong Prov Key Lab Appl Bot, South China Bot Garden, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China.; Yang, ZY (corresponding author), Chinese Acad Sci, Guangdong Prov Key Lab Appl Bot, South China Bot Garden, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Guangdong Food & Drug Vocat Coll, 321 Longdongbei Rd, Guangzhou 510520, Guangdong, Peoples R China;Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
Article
Chinese Acad Sci
AMSTERDAM
null
null
Chinese Acad Sci;Guangdong Food & Drug Vocat Coll;Univ Chinese Acad Sci
China Postdoctoral Science Foundation;Guangdong Natural Science Foundation for Distinguished Young Scholar;National Key Research and Development Program of China;National Natural Science Foundation of China
Yang, ZY (corresponding author), Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China.; Yang, ZY (corresponding author), Chinese Acad Sci, Guangdong Prov Key Lab Appl Bot, South China Bot Garden, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China.
null
Dong, Fang;Gu, Dachuan;Liao, Yinyin;Wang, Xuewen;Yang, Ziyin;Zeng, Lanting
128
5
484,758,500,008
China Postdoctoral Science Foundation [2018M640837];Guangdong Natural Science Foundation for Distinguished Young Scholar [2016A030306039];National Key Research and Development Program of China [2018YFD1000601];National Natural Science Foundation of China [31870684]
China
POSTHARVEST BIOLOGY AND TECHNOLOGY
China
null
null
Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China
0925-5214
Dong, F;Gu, D C;Liao, Y Y;Wang, X W;Yang, Z Y;Zeng, L T
NOV
zyyang@scbg.ac.cn
formation;manufacturing process;oolong tea (<i>Camellia sinensis</i>);phytohormone levels;response
6
J
Agriculture;Food Science & Technology
0.01);0.05);ABA;ABA (p;Abscisic acid;abscisic acid (ABA) levels;activated JA synthetic gene expression;Aroma;Camellia sinensis;characteristic aromas;continuous wounding;defense responses;dehydration stress;enhanced JA synthesis (p;formation;GENE-EXPRESSION;important upstream signals;increase;increased levels;JA;JA (p;Jasmonic acid;jasmonic acid (JA);key upstream signals;LEAF;LEAVES;manufacturing process;manufacturing processes (enzyme-active stage);oolong tea;oolong tea (<i>Camellia sinensis</i>);oolong tea (postharvest stage);phytohormone;phytohormone levels;phytohormones;plant volatiles' biosynthesis;response;SALICYLIC-ACID;Stress;stresses;study;Tea;tea leaves;turn;understanding;Volatile;VOLATILE COMPOUNDS;withering stage activated ABA synthetic gene expression;wounding
Zeng, L T
Abscisic acid;Aroma;Camellia sinensis;GENE-EXPRESSION;Jasmonic acid;LEAF;LEAVES;SALICYLIC-ACID;Tea;Volatile;VOLATILE COMPOUNDS
null
[Zeng, Lanting; Wang, Xuewen; Liao, Yinyin; Gu, Dachuan; Yang, Ziyin] Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China. [Zeng, Lanting; Wang, Xuewen; Liao, Yinyin; Gu, Dachuan; Yang, Ziyin] Chinese Acad Sci, Guangdong Prov Key Lab Appl Bot, South China Bot Garden, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China. [Zeng, Lanting; Yang, Ziyin] Chinese Acad Sci, Ctr Econ Bot, Core Bot Gardens, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China. [Dong, Fang] Guangdong Food & Drug Vocat Coll, 321 Longdongbei Rd, Guangzhou 510520, Guangdong, Peoples R China. [Wang, Xuewen; Liao, Yinyin; Yang, Ziyin] Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China.
This study was supported by the financial support from the National Natural Science Foundation of China (31870684), the National Key Research and Development Program of China (2018YFD1000601), the China Postdoctoral Science Foundation (2018M640837), and the Guangdong Natural Science Foundation for Distinguished Young Scholar (2016A030306039).
0.01);0.05);ABA;ABA (p;abscisic acid (ABA) levels;activated JA synthetic gene expression;characteristic aromas;continuous wounding;defense responses;dehydration stress;enhanced JA synthesis (p;formation;important upstream signals;increase;increased levels;JA;JA (p;jasmonic acid (JA);key upstream signals;manufacturing process;manufacturing processes (enzyme-active stage);oolong tea;oolong tea (postharvest stage);phytohormone;phytohormones;plant volatiles' biosynthesis;response;stress;stresses;study;tea leaves;turn;understanding;withering stage activated ABA synthetic gene expression;wounding
10.1007/s10886-007-9344-8;10.1016/j.foodchem.2012.12.048;10.1016/j.foodchem.2017.03.122;10.1016/j.foodchem.2017.05.137;10.1016/j.foodres.2013.02.011;10.1016/j.jplph.2010.01.003;10.1016/j.plantsci.2017.08.005;10.1016/j.postharvbio.2017.09.005;10.1016/j.tplants.2007.06.001;10.1016/j.tplants.2015.02.001;10.1016/S1360-1385(99)01497-1;10.1021/acs.jafc.5b02741;10.1021/acs.jafc.6b01742;10.1021/acs.jafc.8b00515;10.1021/jf010681x;10.1021/jf203396a;10.1038/224514a0;10.1038/hortres.2014.29;10.1038/nprot.2010.37;10.1039/c7ra03219f;10.1073/pnas.96.26.15354;10.1080/10408398.2018.1506907;10.1093/pcp/pcy091;10.1093/treephys/tpn049;10.1105/tpc.106.049353;10.1111/j.1399-3054.2005.00545.x;10.1126/science.250.4983.1002;10.1128/AEM.00694-08;10.1186/1471-2164-9-550;10.1271/bbb.60708;10.3389/fpls.2015.01248;10.3390/ijms151222155;10.3390/ijms19082440;10.3390/molecules21020124;10.4236/AJAC.2014.59070, 10.4236/ajac.2014.59070];10.7831/RAS.1.1]
Chinese Acad Sci
Dong, F;Gu, D C;Liao, Y Y;Wang, X W;Yang, Z Y;Zeng, L T
Zeng, L T: Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China
Gu, Dachuan;Zeng, lanting
2016A030306039;2018M640837;2018YFD1000601;31870684
41
null
China
Chinese Acad Sci;Guangdong Food & Drug Vocat Coll;Univ Chinese Acad Sci
Zeng, Lanting
null
GENE-EXPRESSION;LEAF;LEAVES;SALICYLIC-ACID;VOLATILE COMPOUNDS
Zeng, Lanting; Wang, Xuewen; Liao, Yinyin; Gu, Dachuan; Dong, Fang; Yang, Ziyin;
null
Chinese Acad Sci, Ctr Econ Bot, Core Bot Gardens, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Chinese Acad Sci, Guangdong Prov Key Lab Appl Bot, South China Bot Garden, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Guangdong Food & Drug Vocat Coll, 321 Longdongbei Rd, Guangzhou 510520, Guangdong, Peoples R China;Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
Chinese Acad Sci, Ctr Econ Bot, Core Bot Gardens, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Chinese Acad Sci, Guangdong Prov Key Lab Appl Bot, South China Bot Garden, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Guangdong Food & Drug Vocat Coll, 321 Longdongbei Rd, Guangzhou 510520, Guangdong, Peoples R China;Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
1873-2356
Abscisic acid;Aroma;Camellia sinensis;Jasmonic acid;Tea;volatiles
null
1969;1990;1999;2002;2003;2005;2007;2008;2009;2010;2011;2013;2014;2015;2016;2017;2018;2019
32
Chinese Acad Sci, Guangdong Prov Key Lab Appl Bot, South China Bot Garden, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China;Chinese Acad Sci, Key Lab South China Agr Plant Mol Anal & Genet Im, 723 Xingke Rd, Guangzhou 510650, Guangdong, Peoples R China
Postharvest Biol. Technol.
Yang, Ziyin
ELSEVIER
(ABA);(enzyme-active;(JA);(p;(postharvest;,;0.01);0.05);<;=;ABA;abscisic;acid;activated;advances;an;and;aromas;as;biosynthesis;characteristic;continuous;defense;dehydration;due;during;enhanced;expression;formation;from;further;gene;important;in;increase;increased;investigates;is;JA;jasmonic;key;leaves;levels;manufacturing;of;oolong;over;phytohormone;phytohormones;plant;plucking;process;processes;regulate;response;responses;resulting;signals;some;stage;stage);stress;stresses;study;synthesis;synthetic;tea;the;this;to;turn;under;understanding;upstream;various;volatiles';withering;wounding
Chinese Acad Sci
As important upstream signals, phytohormones regulate the plant volatiles' biosynthesis under various stresses. The formation of some characteristic aromas during the manufacturing process of oolong tea (postharvest stage) is due to the defense responses of tea leaves to stress. This study investigates the formation of phytohormone in response to stresses during the manufacturing process of oolong tea. Jasmonic acid (JA) and abscisic acid (ABA) levels enhanced during the manufacturing processes (enzyme-active stage) of oolong tea. Wounding from plucking activated JA synthetic gene expression, resulting in increased levels of JA (p <= 0.01), and continuous wounding from the turn over stage further enhanced JA synthesis (p <= 0.05). Dehydration stress during the withering stage activated ABA synthetic gene expression resulting in an increase of ABA (p <= 0.01). The study advances the understanding of key upstream signals, JA and ABA, during the manufacturing process of oolong tea.
AAH-5092-2021;JAA-9491-2023
GENE-EXPRESSION;LEAF;LEAVES;SALICYLIC-ACID;VOLATILE COMPOUNDS
3
null
Abscisic acid;Aroma;Camellia sinensis;Jasmonic acid;Tea;Volatile
8
ABSCISIC-ACID;Aroma;Camellia sinensis;GENE-EXPRESSION;Jasmonic acid;LEAF;LEAVES;SALICYLIC-ACID;Tea;volatiles;VOLATILE COMPOUNDS
WOS:000484758500008
Chinese Acad Sci, Guangdong, Peoples R China;Guangdong Food & Drug Vocat Coll, Guangdong, Peoples R China;Univ Chinese Acad Sci, Beijing, Peoples R China
China
2,019
null
null
null
null
English
null
AM J ANAL CHEM;APPL ENVIRON MICROB;BIOSCI BIOTECH BIOCH;BMC GENOMICS;CRIT REV FOOD SCI;FOOD CHEM;FOOD RES INT;FRONT PLANT SCI;HORTIC RES-ENGLAND;INT J MOL SCI;INT J PLANT PROD;J AGR FOOD CHEM;J CHEM ECOL;J PLANT PHYSIOL;MOLECULES;NAT PROTOC;NATURE;P NATL ACAD SCI USA;PHYSIOL PLANTARUM;PLANT CELL;PLANT CELL PHYSIOL;PLANT HORMONES BIOSY;PLANT SCI;POSTHARVEST BIOL TEC;READING AND DYSLEXIA IN DIFFERENT ORTHOGRAPHIES;RSC ADV;SCIENCE;STRESS PHYSL TEA FAC;Tea Biochemistry;TREE PHYSIOL;TRENDS PLANT SCI
Dong, Fang;Gu, Dachuan;Liao, Yinyin;Wang, Xuewen;Yang, Ziyin;Zeng, Lanting
2024-03-11 ER
Baldermann S.;Barua, D N;Bömke, C;Cho, J Y;Constantinou, S;Cutler, A J;Dong, F;Ghanati, F;Gui, J D;Han, B Y;Hao, X Y;Huerta, L;Ishiwari, H;Kazan, K;Maffei, M E;Malamy, J;Mcdougall, S;Noguerol-Pato, R;Pan, X Q;Peng, Q Y;Pál, M;Qin, X Q;Schwartz S., H;Upadhyaya H.;Wan X.C.;Wang, D L;Wu, J Q;Xiao, Y H;Xue, T T;Yang, Z Y;Zeng, L T;Zhang L.;Zhou, L;Zhou, Y;Zhu, J Y
IW1VM
Guangdong, Peoples R China;Guangdong, Peoples R China.
37
null
3
null
null
Dong, Fang;Gu, Dachuan;Liao, Yinyin;Wang, Xuewen;Yang, Ziyin;Zeng, Lanting
POSTHARVEST BIOL TEC
Beijing, Peoples R China;Guangdong, Peoples R China
Cao, Y B;Guo, Y K;Huang, H Y;Liao, W X;Liu, Q;Liu, Y Q;Lu, Y Y;Xie, Z
10.1038/s41467-019-12794-2
4801
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
2ord1n1sg3w630r1224242oy6q6o2a1d6r
Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapy
Tsinghua Univ
null
Xie, Z (corresponding author), Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China.;Xie, Z (corresponding author), Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China.
null
Cao, Yubing;Guo, Yakun;Huang, Huiya;Liao, Weixi;Liu, Qiang;Liu, Yiqi;Lu, Yinying;Xie, Zhen
Multidisciplinary Sciences
Tsinghua National Laboratory for Information Science and Technology Bioinformatics Public Instrument Platform, Tsinghua Biomedical Sciences Public Instrument Platform, Tsinghua Animal Facility; National Natural Science Foundation of China [61721003]; Basic Research Program of Tsinghua National Lab for Information Science and Technology; Syngentech Inc.
WOS
Xie, Z
PLA Genaral Hosp, Beijing, Peoples R China;Syngentech Inc, Beijing, Peoples R China;Tsinghua Univ, Beijing, Peoples R China
10
adenovirus;by;cancer;circuit;for;gene;immunotherapy;oncolytic;programmed;synthetic
1
null
NATURE PUBLISHING GROUP
PLA Genaral Hosp, Comprehens Liver Canc Ctr, Med Ctr 5, 100 Xi Si Huan Middle Rd, Beijing 100039, Peoples R China;Syngentech Inc, Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China;Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China;Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China;Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China.; Xie, Z (corresponding author), Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China
Article
Tsinghua Univ
LONDON
null
null
PLA Genaral Hosp;Syngentech Inc;Tsinghua Univ
Basic Research Program of Tsinghua National Lab for Information Science and Technology;National Natural Science Foundation of China;Syngentech Inc.;Tsinghua National Laboratory for Information Science and Technology Bioinformatics Public Instrument Platform, Tsinghua Biomedical Sciences Public Instrument Platform, Tsinghua Animal Facility
Xie, Z (corresponding author), Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China.; Xie, Z (corresponding author), Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China.
null
Cao, Yubing;Guo, Yakun;Huang, Huiya;Liao, Weixi;Liu, Qiang;Liu, Yiqi;Lu, Yinying;Xie, Zhen
52
4
491,306,200,009
Basic Research Program of Tsinghua National Lab for Information Science and Technology;National Natural Science Foundation of China [61721003];Syngentech Inc.;Tsinghua National Laboratory for Information Science and Technology Bioinformatics Public Instrument Platform, Tsinghua Biomedical Sciences Public Instrument Platform, Tsinghua Animal Facility
China
NATURE COMMUNICATIONS
China
null
null
Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China
2041-1723
Cao, Y B;Guo, Y K;Huang, H Y;Liao, W X;Liu, Q;Liu, Y Q;Lu, Y Y;Xie, Z
OCT 22
zhenxie@tsinghua.edu.cn
cancer immunotherapy;oncolytic adenovirus;synthetic gene circuit
8
J
Science & Technology - Other Topics
adenoviral replication;ALPHA;ANTIBODY;CANCER;cancer immunotherapy;cancers;COLONY-STIMULATING FACTOR;combinatorial treatment;combining tumor lysis;computational simulations;DELIVERY;difficulty increasing specificity;effective strategy;hepatocellular carcinoma cells;HEPATOCELLULAR-CARCINOMA;IDENTIFICATION;immune effector;immune effectors;immune responses;immunocompetent mouse models;immunomodulators;improving efficacy;innovative immunotherapies;lead;limited understanding;LIVER;local lymphocyte cytotoxicity;microRNA inputs;modular synthetic gene circuits;multiple promoter;non-replicable adenovirus;oncolytic adenovirus;oncolytic virotherapy;oncolytic virus;performing mouse model experiments;population dynamics;programmable;release;replicable adenovirus;REPLICATIVE ADENOVIRUS;response;results;robust therapeutic efficacy;secretion;superior tumor-killing efficacy;synergistic effect;Synthetic gene circuit;systematic vaccination;variety;virus
Huang, H Y
ALPHA;ANTIBODY;COLONY-STIMULATING FACTOR;DELIVERY;HEPATOCELLULAR-CARCINOMA;IDENTIFICATION;LIVER;REPLICATIVE ADENOVIRUS;virus
null
[Huang, Huiya; Liao, Weixi; Xie, Zhen] Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China. [Huang, Huiya; Liao, Weixi; Xie, Zhen] Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China. [Liu, Yiqi; Cao, Yubing; Liu, Qiang; Guo, Yakun] Syngentech Inc, Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China. [Lu, Yinying] PLA Genaral Hosp, Comprehens Liver Canc Ctr, Med Ctr 5, 100 Xi Si Huan Middle Rd, Beijing 100039, Peoples R China.
We thank members of Xie lab for helpful discussions. We thank Huixin Geng for technical support. The research was supported by Tsinghua National Laboratory for Information Science and Technology Bioinformatics Public Instrument Platform, Tsinghua Biomedical Sciences Public Instrument Platform, Tsinghua Animal Facility. The financial supports were provided by Syngentech Inc., National Natural Science Foundation of China (61721003) and the Basic Research Program of Tsinghua National Lab for Information Science and Technology.
adenoviral replication;cancer;cancers;combinatorial treatment;combining tumor lysis;computational simulations;difficulty increasing specificity;effective strategy;hepatocellular carcinoma cells;immune effector;immune effectors;immune responses;immunocompetent mouse models;immunomodulators;improving efficacy;innovative immunotherapies;lead;limited understanding;local lymphocyte cytotoxicity;microRNA inputs;modular synthetic gene circuits;multiple promoter;non-replicable adenovirus;oncolytic adenovirus;oncolytic virotherapy;oncolytic virus;performing mouse model experiments;population dynamics;programmable;release;replicable adenovirus;response;results;robust therapeutic efficacy;secretion;superior tumor-killing efficacy;synergistic effect;systematic vaccination;variety
10.1006/mthe.2000.0130;10.1007/s002850050127;10.1016/j.canlet.2016.07.019;10.1016/j.ccr.2011.01.001;10.1016/j.cell.2007.04.040;10.1016/j.cell.2012.08.040;10.1016/j.cell.2017.08.027;10.1016/j.cell.2017.09.049;10.1016/j.celrep.2016.07.061;10.1016/j.ejca.2016.02.025;10.1016/j.omto.2016.12.004;10.1021/acssynbio.7b00134;10.1038/cgt.2011.67;10.1038/cgt.2014.34;10.1038/nature10358;10.1038/nature14011;10.1038/nature24649;10.1038/nbt.3301;10.1038/nbt957;10.1038/nchembio.1680;10.1038/nchembio.1736;10.1038/ncomms10456;10.1038/ncomms14754;10.1038/ncomms6293;10.1038/nm.1776;10.1038/nm.3089;10.1038/nm.4015;10.1038/nrclinonc.2016.58;10.1038/nrd.2016.254;10.1038/nrd4663;10.1038/sj.gt.3300870;10.1038/sj.gt.3302001;10.1056/NEJMoa1709684;10.1073/pnas.1604391113;10.1098/rsif.2017.0150;10.1101/gad.7.4.546;10.1126/science.1205527;10.1126/science.274.5286.373;10.1128/JVI.67.10.5911-5921.1993;10.1158/0008-5472.CAN-16-1708;10.1158/0008-5472.CAN-17-1662;10.1158/1078-0432.CCR-05-1059;10.1158/1535-7163.MCT-12-0157;10.1200/JCO.2014.58.3377;10.1200/JCO.2015.61.6870;10.1371/journal.pone.0005553;10.1371/journal.pone.0073964
Tsinghua Univ
Cao, Y B;Guo, Y K;Huang, H Y;Liao, W X;Liu, Q;Liu, Y Q;Lu, Y Y;Xie, Z
Huang, H Y: Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China
Liu, Yiqi;Xie, Zhen
61721003
48
null
China
PLA Genaral Hosp;Syngentech Inc;Tsinghua Univ
Huang, Huiya
gold, Green Published
ALPHA;ANTIBODY;COLONY-STIMULATING FACTOR;DELIVERY;HEPATOCELLULAR-CARCINOMA;IDENTIFICATION;LIVER;REPLICATIVE ADENOVIRUS;VIRUS
Huang, Huiya; Liu, Yiqi; Liao, Weixi; Cao, Yubing; Liu, Qiang; Guo, Yakun; Lu, Yinying; Xie, Zhen;
null
PLA Genaral Hosp, Comprehens Liver Canc Ctr, Med Ctr 5, 100 Xi Si Huan Middle Rd, Beijing 100039, Peoples R China;Syngentech Inc, Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China;Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China;Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China
PLA Genaral Hosp, Comprehens Liver Canc Ctr, Med Ctr 5, 100 Xi Si Huan Middle Rd, Beijing 100039, Peoples R China;Syngentech Inc, Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China;Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China;Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China
null
null
null
1993;1996;1998;1999;2000;2001;2003;2004;2006;2007;2008;2009;2011;2012;2013;2014;2015;2016;2017;2018
56
Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China;Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, Dept Automat,Beijing Natl Res Ctr Informat Sci &, Beijing 100084, Peoples R China
Nat. Commun.
Xie, Zhen
NATURE PUBLISHING GROUP
,;a;adenoviral;adenovirus;against;an;and;by;can;cancer;cancers;carcinoma;cells;challenging;circuits;combinatorial;combining;computational;construct;control;cytotoxicity;difficulty;due;dynamics;effect;effective;effector;effectors;efficacy;encodes;engineer;exert;experiments;find;for;furthermore;gene;has;hepatocellular;here;immune;immunocompetent;immunomodulators;immunotherapies;improving;in;increasing;innovative;inputs;its;lead;limited;local;lymphocyte;lysis;may;microRNA;model;models;modular;more;mouse;multiple;non-replicable;observe;of;on;oncolytic;our;performing;population;programmable;promoter;promoting;provide;release;remains;replicable;replication;response;responses;results;robust;secretion;selectively;show;simulations;specificity;strategy;superior;synergistic;synthetic;systematic;than;that;therapeutic;to;treatment;tumor;tumor-killing;understanding;vaccination;variety;virotherapy;virus;we;which;with
Tsinghua Univ
Improving efficacy of oncolytic virotherapy remains challenging due to difficulty increasing specificity and immune responses against cancer and limited understanding of its population dynamics. Here, we construct programmable and modular synthetic gene circuits to control adenoviral replication and release of immune effectors selectively in hepatocellular carcinoma cells in response to multiple promoter and microRNA inputs. By performing mouse model experiments and computational simulations, we find that replicable adenovirus has a superior tumor-killing efficacy than non-replicable adenovirus. We observe a synergistic effect on promoting local lymphocyte cytotoxicity and systematic vaccination in immunocompetent mouse models by combining tumor lysis and secretion of immunomodulators. Furthermore, our computational simulations show that oncolytic virus which encodes immunomodulators can exert a more robust therapeutic efficacy than combinatorial treatment with oncolytic virus and immune effector. Our results provide an effective strategy to engineer oncolytic adenovirus, which may lead to innovative immunotherapies for a variety of cancers.
AAK-1630-2020;GPW-5925-2022
ALPHA;ANTIBODIES;COLONY-STIMULATING FACTOR;DELIVERY;HEPATOCELLULAR-CARCINOMA;IDENTIFICATION;LIVER;REPLICATING ADENOVIRUS;VIRUS
1
null
null
15
ALPHA;ANTIBODIES;COLONY-STIMULATING FACTOR;DELIVERY;HEPATOCELLULAR-CARCINOMA;IDENTIFICATION;LIVER;REPLICATING ADENOVIRUS;virus
WOS:000491306200009
PLA Genaral Hosp, Beijing, Peoples R China;Syngentech Inc, Beijing, Peoples R China;Tsinghua Univ, Beijing, Peoples R China
China
2,019
null
null
null
null
English
null
ACS SYNTH BIOL;CANCER CELL;CANCER GENE THER;CANCER LETT;CANCER RES;CELL;CELL REP;CLIN CANCER RES;EUR J CANCER;GENE DEV;GENE THER;J CLIN ONCOL;J MATH BIOL;J R SOC INTERFACE;J VIROL;MOL CANCER THER;MOL THER;MOL THER-ONCOLYTICS;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT MED;NAT REV CLIN ONCOL;NAT REV DRUG DISCOV;NATURE;NEW ENGL J MED;P NATL ACAD SCI USA;PLOS ONE;SCIENCE
Cao, Yubing;Guo, Yakun;Huang, Huiya;Liao, Weixi;Liu, Qiang;Liu, Yiqi;Lu, Yinying;Xie, Zhen
2024-03-11 ER
Andtbacka, R H I;Angelici, B;Bett, A J;Bischoff, J R;Boutros, C;Breitbach, C J;Callegari, E;Chau, A H;Chiou, V L;Debbas, M;Dolgin, E;Du, T;Engler, C;Fajardo, C A;Guo, Y C;Havunen, R;Heo, J;Herbst, R S;Hofmann, L;Hou, J;Ishikawa, H;Kaufman, H L;Kelly, E J;Kirschner, D;Klebanoff, C A;Konstorum, A;Landgraf, P;Lapique, N;Li, Y Q;Liao, W X;Liu, X;Liu, Y H;Liu, Z Q;Ma, D;Morel, M;Nagayama, Y;Nissim, L;Ramesh, N;Ribas, A;Szymczak, A L;Toda, M;Wartewig, T;Wodarz, D;Wolchok, J D;Wroblewska, L;Xie, Z;Yuan, X F;Zhang, Z W
JF3SB
Beijing, Peoples R China;Beijing, Peoples R China.
63
null
3
null
31,641,136
Cao, Yubing;Guo, Yakun;Huang, Huiya;Liao, Weixi;Liu, Qiang;Liu, Yiqi;Lu, Yinying;Xie, Zhen
NAT COMMUN
Beijing, Peoples R China
Dickinson, B C;Jones, K A;Zinkus-Boltz, J
10.1088/2399-1984/ab4b78
042002
TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
2y6601ymo634xq168f1q341j1w5461l4t
Recent advances in developing and applying biosensors for synthetic biology
Univ Chicago
null
Dickinson, BC (corresponding author), Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
null
Dickinson, Bryan C;Jones, Krysten A;Zinkus-Boltz, Julia
Materials Science, Multidisciplinary;Nanoscience & Nanotechnology;Physics, Applied
University of Chicago; National Institute of Mental Health [RF1 MH114102]; National Cancer Institute of the National Institutes of Health [R21 CA217754]
WOS
Dickinson, B C
Univ Chicago, Chicago, IL USA
3
advances;and;applying;biology;biosensors;developing;for;in;recent;synthetic
1
Jones, Krysten;Zinkus-Boltz, Julia
IOP PUBLISHING LTD
Univ Chicago, Dept Chem, Chicago, IL 60637 USA
Review
Univ Chicago
BRISTOL
null
null
Univ Chicago
National Cancer Institute of the National Institutes of Health;National Institute of Mental Health;University of Chicago
Dickinson, BC (corresponding author), Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
null
Dickinson, Bryan C;Jones, Krysten A;Zinkus-Boltz, Julia
55
1
517,260,400,002
National Cancer Institute of the National Institutes of Health [R21 CA217754];National Institute of Mental Health [RF1 MH114102];University of Chicago
USA
NANO FUTURES
USA
null
null
Univ Chicago, Dept Chem, Chicago, IL 60637 USA
null
Dickinson, B C;Jones, K A;Zinkus-Boltz, J
OCT
Dickinson@uchicago.edu
biosensors;developing;recent advances;synthetic biology
3
J
Materials Science;Physics;Science & Technology - Other Topics
advancements;applications;biological engineering efforts;BIOLOGY;biosensors;cellular signaling pathways;chemical biology;clinical applications;CONDITIONAL EXPRESSION;CRYSTAL-STRUCTURE;developing;directed evolution;ENZYME PRODRUG THERAPY;evolutionary methods;flexible biosensors;Gene circuits;host organisms;IN-VIVO;indispensable component;input signals;molecular protein scaffolds;naturally-occurring biological processes;PROTEIN-PROTEIN INTERACTIONS;rational design;recent advances;recent innovations;review;SPLIT-LUCIFERASE;STRUCTURAL BASIS;synthetic biologist's toolbox;synthetic biology;synthetic biology tools;synthetic gene circuits;T7 RNA-POLYMERASE;tractable outputs;utility across basic biological research;wide range
Jones, K A
biosensors;chemical biology;CONDITIONAL EXPRESSION;CRYSTAL-STRUCTURE;directed evolution;ENZYME PRODRUG THERAPY;Gene circuits;IN-VIVO;PROTEIN-PROTEIN INTERACTIONS;SPLIT-LUCIFERASE;STRUCTURAL BASIS;Synthetic biology;T7 RNA-POLYMERASE
null
[Jones, Krysten A.; Zinkus-Boltz, Julia; Dickinson, Bryan C.] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
This work was supported by the University of Chicago, the National Institute of Mental Health (RF1 MH114102) and the National Cancer Institute (R21 CA217754) of the National Institutes of Health.
advancements;applications;biological engineering efforts;biology;biosensors;cellular signaling pathways;clinical applications;evolutionary methods;flexible biosensors;host organisms;indispensable component;input signals;molecular protein scaffolds;naturally-occurring biological processes;rational design;recent innovations;review;synthetic biologist's toolbox;synthetic biology tools;synthetic gene circuits;tractable outputs;utility across basic biological research;wide range
10.1002/1873-3468.12548;10.1002/biot.201700432;10.1002/biot.201700561;10.1002/biot.201700648;10.1002/bit.25676;10.1002/bit.26340;10.1002/cbic.200700713;10.1002/cbic.201000041;10.1002/cbic.201000642;10.1002/cbic.201800707;10.1007/978-1-4939-6940-1_14;10.1007/s00216-014-7980-8;10.1007/s00253-015-7090-3;10.1007/s11095-005-6156-9;10.1007/s13238-015-0153-5;10.1007/s13353-016-0341-x;10.1016/0022-2836(86)90385-2;10.1016/j.addr.2016.04.032;10.1016/j.biochi.2018.09.001;10.1016/j.biortech.2017.06.114;10.1016/j.biotechadv.2016.08.003;10.1016/j.biotechadv.2018.10.001;10.1016/j.bmcl.2008.12.057;10.1016/j.cbpa.2011.10.014;10.1016/j.cbpa.2013.09.012;10.1016/j.cbpa.2015.05.013;10.1016/j.ceca.2008.02.002;10.1016/j.cell.2010.07.014;10.1016/j.cell.2013.04.025;10.1016/j.cell.2013.06.044;10.1016/j.cell.2014.01.027;10.1016/j.cell.2014.02.001;10.1016/j.cell.2014.02.039;10.1016/j.cell.2015.08.007;10.1016/j.cell.2016.01.011;10.1016/j.cell.2016.01.012;10.1016/j.cell.2016.09.011;10.1016/j.cell.2016.11.017;10.1016/j.cell.2016.12.009;10.1016/j.cell.2017.03.041;10.1016/j.cell.2017.09.049;10.1016/j.cell.2018.02.033;10.1016/j.cell.2018.11.052;10.1016/j.cell.2019.04.009;10.1016/j.cell.2019.05.049;10.1016/j.celrep.2013.06.020;10.1016/j.cels.2015.06.001;10.1016/j.chembiol.2014.12.011;10.1016/j.copbio.2014.12.021;10.1016/j.copbio.2016.03.005;10.1016/j.jmb.2005.10.076;10.1016/j.jmb.2018.06.037;10.1016/j.molcel.2014.04.022;10.1016/j.molcel.2018.09.018;10.1016/j.sbi.2009.09.001;10.1016/j.sbi.2019.01.013;10.1016/j.tibtech.2010.10.004;10.1016/j.tibtech.2013.01.018;10.1016/j.tibtech.2015.12.014;10.1016/j.tig.2016.01.005;10.1016/S0076-6879(00)28399-7;10.1016/S0079-6603(03)01001-8;10.1016/S0092-8674(04)00059-5;10.1016/S0092-8674(04)00120-5;10.1016/S0959-440X(00)00235-9;10.1021/ac000617z;10.1021/ac0013296;10.1021/ac010717k;10.1021/acs.biochem.8b01202;10.1021/acs.molpharmaceut.5b00464;10.1021/acscentsci.7b00058;10.1021/acscentsci.7b00107;10.1021/acscentsci.9b00567;10.1021/acschembio.5b00753;10.1021/acschembio.5b01019;10.1021/acschembio.7b00532;10.1021/acschembio.8b00524;10.1021/acschembio.8b00919;10.1021/acssynbio.6b00248;10.1021/acssynbio.6b00279;10.1021/acssynbio.7b00059;10.1021/acssynbio.7b00136;10.1021/acssynbio.7b00169;10.1021/acssynbio.8b00242;10.1021/bi000365w;10.1021/bi00415a055;10.1021/cb800065s;10.1021/ja805203w;10.1021/ja994421w;10.1021/jacs.5b02774;10.1021/jacs.5b10290;10.1021/jacs.7b06152;10.1021/jacs.7b06555;10.1021/jacs.8b05012;10.1021/sb200016s;10.1021/sb400077j;10.1021/sb400081r;10.1021/sb400128g;10.1021/sb500299c;10.1038/19999;10.1038/228227a0;10.1038/346818a0;10.1038/364593a0;10.1038/cr.2013.122;10.1038/gt.2011.101;10.1038/mi.2009.116;10.1038/msb.2008.62;10.1038/mt.2011.256;10.1038/nature01129;10.1038/nature09929;10.1038/nature14592;10.1038/nature24049;10.1038/nature26155;10.1038/nbt.2501;10.1038/nbt.2510;10.1038/nbt.2623;10.1038/nbt.2689;10.1038/nbt.3245;10.1038/nbt.3404;10.1038/nbt.3563;10.1038/nbt.3879;10.1038/nbt.4222;10.1038/nbt0602-619;10.1038/nchembio.1753;10.1038/nchembio.2299;10.1038/nchembio.2390;10.1038/ncomms12009;10.1038/ncomms13056;10.1038/ncomms14370;10.1038/ncomms1516;10.1038/ncomms15690;10.1038/ncomms5240;10.1038/nmeth.2532;10.1038/nmeth.3993;10.1038/nmeth932;10.1038/nmeth967;10.1038/nprot.2009.239;10.1038/nprot.2017.119;10.1038/nrm3738;10.1038/nrmicro3239;10.1038/nsmb.3014;10.1038/s41467-018-03069-3;10.1038/s41467-018-04252-2;10.1038/s41467-018-05466-0;10.1038/s41467-018-05525-6;10.1038/s41467-018-07473-7;10.1038/s41467-018-07610-2;10.1038/s41557-018-0174-9;10.1038/s41564-017-0004-7;10.1038/s41564-018-0216-5;10.1038/s41589-018-0046-z;10.1038/s41589-018-0121-5;10.1038/s41589-018-0181-6;10.1038/s41592-018-0301-y;10.1038/sj.cgt.7700685;10.1038/sj.gt.3300569;10.1038/srep02854;10.1039/c1mb05070b;10.1039/c3cs35528d;10.1039/c3cs60141b;10.1039/c4an01418a;10.1042/EBC20150001;10.1049/ip-nbt:20050047;10.1053/j.gastro.2012.06.037;10.1073/pnas.0402940101;10.1073/pnas.0700293104;10.1073/pnas.0710487105;10.1073/pnas.1111943109;10.1073/pnas.1220157110;10.1073/pnas.1321321111;10.1073/pnas.1417910112;10.1073/pnas.1501698112;10.1073/pnas.1508521112;10.1073/pnas.1600375113;10.1073/pnas.77.5.2819;10.1073/pnas.81.7.2035;10.1073/pnas.95.1.352;10.1073/pnas.97.9.4826;10.1074/jbc.C200588200;10.1074/jbc.M400139200;10.1089/10430349950018968;10.1089/hum.2015.087;10.1093/hmg/ddv120;10.1093/nar/25.6.1203;10.1093/nar/gkh094;10.1093/nar/gkn924;10.1093/nar/gks597;10.1093/nar/gks636;10.1093/nar/gkt101;10.1093/nar/gkt135;10.1093/nar/gkt780;10.1093/nar/gku402;10.1093/nar/gku884;10.1093/nar/gkv1289;10.1093/nar/gkv601;10.1093/nar/gkv616;10.1093/nar/gkw117;10.1093/nar/gkw1267;10.1097/CJI.0b013e31819b7c8e;10.1101/cshperspect.a032532;10.1111/bph.13553;10.1126/science.1077464;10.1126/science.1138140;10.1126/science.1163433;10.1126/science.1179555;10.1126/science.1225829;10.1126/science.1247997;10.1126/science.1258096;10.1126/science.2200121;10.1126/science.273.5272.239;10.1126/science.286.5448.2305;10.1126/science.289.5483.1352;10.1126/science.aad1067;10.1126/science.aaf5573;10.1126/science.aaq0180;10.1126/science.aat0271;10.1126/science.aat5062;10.1126/scisignal.2001449;10.1126/scitranslmed.3005568;10.1128/AEM.01019-08;10.1128/jb.174.2.619-622.1992;10.1128/mBio.02321-18;10.1128/mSystems.00125-19;10.1136/gutjnl-2015-309990;10.1146/annurev-biochem-060614-034411;10.1146/annurev-immunol-051116-052302;10.1146/annurev-neuro-071013-014048;10.1146/annurev-virology-101416-041616;10.1152/physrev.00009.2017;10.1158/0008-5472.CAN-12-2649;10.1158/1078-0432.CCR-12-2422;10.1186/1471-2105-7-S2-S6;10.1186/s13104-018-3965-6;10.1210/en.2007-0235;10.1261/rna.2433111;10.1371/journal.pone.0131037;10.15252/msb.20145299;10.1534/genetics.113.152710;10.2116/analsci.30.539;10.2144/000112036;10.2174/1389200033489253;10.3389/fmicb.2015.00685;10.3390/foods7090141;10.3390/genes9070351;10.3390/genes9080375;10.3390/molecules23123178;10.3390/s17122918;10.7554/eLife.10606;10.7554/eLife.43826;[10.1038/NCHEMBIO.1453, 10.1038/nchembio.1453];[10.1038/NCHEMBIO.1793, 10.1038/nchembio.1793];[10.1038/NCHEMBIO.2253, 10.1038/nchembio.2253];[10.1038/NCHEMBIO.2565, 10.1038/nchembio.2565];[10.1038/NMETH.2205, 10.1038/nmeth.2205];[10.1038/nmeth.2598, 10.1038/NMETH.2598];[10.1038/nmeth.2600, 10.1038/NMETH.2600];[10.1038/NMETH.2969, 10.1038/nmeth.2969];[10.1038/NMETH.3486, 10.1038/nmeth.3486];[10.1038/NMETH.3580, 10.1038/nmeth.3580];[10.1038/NMETH.3994, 10.1038/nmeth.3994];[10.1038/NMETH.4042, 10.1038/nmeth.4042];[10.1038/NMETH.4430, 10.1038/nmeth.4430];[10.1038/NMICROBIOL.2016.85, 10.1038/nmicrobiol.2016.85];[10.1146/annurev.bioeng-071811-150118, 10.1146/annurev-bioeng-071811-150118];[10.2144/0000113943, 10.2144/000113943]
Univ Chicago
Dickinson, B C;Jones, K A;Zinkus-Boltz, J
Jones, K A: Univ Chicago, Dept Chem, Chicago, IL 60637 USA
null
R21 CA217754;RF1 MH114102
271
null
USA
Univ Chicago
Jones, Krysten A
null
CONDITIONAL EXPRESSION;CRYSTAL-STRUCTURE;DIRECTED EVOLUTION;ENZYME PRODRUG THERAPY;GENE CIRCUITS;IN-VIVO;PROTEIN-PROTEIN INTERACTIONS;SPLIT-LUCIFERASE;STRUCTURAL BASIS;T7 RNA-POLYMERASE
Jones, Krysten A.; Zinkus-Boltz, Julia; Dickinson, Bryan C.;
null
Univ Chicago, Dept Chem, Chicago, IL 60637 USA
Univ Chicago, Dept Chem, Chicago, IL 60637 USA
2399-1984
Biosensor;chemical biology;directed evolution;Synthetic biology
4
1970;1980;1984;1986;1987;1988;1990;1991;1992;1993;1996;1997;1998;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
7
Univ Chicago, Dept Chem, Chicago, IL 60637 USA
Nano Futures
Dickinson, Bryan C
IOP PUBLISHING LTD
,;a;across;advancements;an;and;applications;are;basic;be;biological;biologist's;biology;biosensors;by;can;cellular;circuits;clinical;compiled;component;customized;design;efforts;engineering;evolutionary;flexible;for;gene;generation;harnessed;have;host;in;including;indispensable;informed;innovations;input;into;introduce;led;methods;molecular;naturally-occurring;of;organisms;outputs;pathways;processes;protein;range;rational;recent;reliable;research;review;robust;scaffolds;signaling;signals;synthetic;tailored;that;the;these;this;through;to;toolbox;tools;tractable;translate;using;utility;we;wide
Univ Chicago
Biosensors are an indispensable component of the synthetic biologist's toolbox. Informed by biology and customized through rational design and evolutionary methods, these molecular protein scaffolds translate input signals into tractable outputs. By using biosensors to introduce synthetic gene circuits and cellular signaling pathways into host organisms, naturally-occurring biological processes can be harnessed and tailored for a wide range of applications. In this review, we have compiled recent innovations and advancements that have led to the generation of robust, reliable, and flexible biosensors for utility across basic biological research and synthetic biology tools, including biological engineering efforts and clinical applications.
null
CONDITIONAL EXPRESSION;CRYSTAL-STRUCTURE;DIRECTED EVOLUTION;ENZYME PRODRUG THERAPY;GENE CIRCUITS;IN-VIVO;PROTEIN-PROTEIN INTERACTIONS;SPLIT-LUCIFERASE;STRUCTURAL BASIS;T7 RNA-POLYMERASE
6
null
biosensors;chemical biology;directed evolution;Synthetic biology
21
Biosensor;chemical biology;CONDITIONAL EXPRESSION;CRYSTAL-STRUCTURE;directed evolution;ENZYME PRODRUG THERAPY;Gene circuits;IN-VIVO;PROTEIN-PROTEIN INTERACTIONS;Split luciferase;STRUCTURAL BASIS;Synthetic biology;T7 RNA-POLYMERASE
WOS:000517260400002
Univ Chicago, Chicago, IL USA
USA
2,019
null
0000-0003-0028-5360;0000-0003-0711-5516
null
null
English
null
ACS CENTRAL SCI;ACS CHEM BIOL;ACS SYNTH BIOL;ADV DRUG DELIVER REV;ANAL BIOANAL CHEM;ANAL CHEM;ANAL SCI;ANALYST;ANNU REV BIOCHEM;ANNU REV BIOMED ENG;ANNU REV IMMUNOL;ANNU REV NEUROSCI;ANNU REV VIROL;APPL ENVIRON MICROB;APPL MICROBIOL BIOT;BIOCHEMISTRY-US;BIOCHIMIE;BIOORG MED CHEM LETT;BIORESOURCE TECHNOL;BIOTECHNIQUES;BIOTECHNOL ADV;BIOTECHNOL BIOENG;BIOTECHNOL J;BMC BIOINFORMATICS;BMC Res Notes;BRIT J PHARMACOL;CANCER GENE THER;CANCER RES;CELL;CELL CALCIUM;CELL REP;CELL RES;CELL SYST;CHEM BIOL;CHEM SOC REV;CHEMBIOCHEM;CLIN CANCER RES;CSH PERSPECT BIOL;CURR DRUG METAB;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;CURR OPIN STRUC BIOL;ELIFE;ENDOCRINOLOGY;ESSAYS BIOCHEM;FEBS LETT;FOODS;FRONT MICROBIOL;GASTROENTEROLOGY;GENE THER;GENES-BASEL;GENETICS;GUT;HUM GENE THER;HUM MOL GENET;IEE P-NANOBIOTECHNOL;INHIBITION PROTEIN P;J AM CHEM SOC;J APPL GENET;J BACTERIOL;J BIOL CHEM;J IMMUNOTHER;J MOL BIOL;MBIO;METHOD ENZYMOL;METHODS MOL BIOL;MOL BIOSYST;MOL CELL;MOL PHARMACEUT;MOL SYST BIOL;MOL THER;MOLECULES;MSYSTEMS;MUCOSAL IMMUNOL;NAT BIOTECHNOL;NAT CHEM;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT MICROBIOL;NAT PROTOC;NAT REV MICROBIOL;NAT REV MOL CELL BIO;NAT STRUCT MOL BIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;P NATL ACAD SCI-BIOL;PHARM RES-DORDR;PHYSIOL REV;PLOS ONE;PROG NUCLEIC ACID RE;PROTEIN CELL;RNA;SCI REP-UK;SCI SIGNAL;SCI TRANSL MED;SCIENCE;SENSORS-BASEL;TRENDS BIOTECHNOL;TRENDS GENET
Dickinson, Bryan C;Jones, Krysten A;Zinkus-Boltz, Julia
2024-03-11 ER
Abil, Z;Abudayyeh, O O;Adli, M;Alam, K K;Anderson, J C;Arkin, A P;Armbruster, B N;Atasoy, D;Ausländer, S;Azad, T;Azzolini, M;Barnea, G;Barrangou, R;Bassett, A R;Baumschlager, A;Bayat, P;Beaumont, K;Beisel, C L;Bhalla, N;Bhaumik, S;Billerbeck, S;Boehm, C R;Borges, A L;Borujeni, A E;Brophy, J A N;Cabantous, S;Cameron, D E;Carlson, J C;Carpenter, A C;Carpenter, R O;Chamberl.M;Chandler, M;Chang, Z N L;Cheetham, G M T;Chen, T J;Chen, Y C;Cheng, A A;Cheng, A W;Cheng, F;Chew, W L;Chmielewski, M;Choi, J W;Chou, C J;Claeysen, S;Coward, P;Cox, D B T;Dahl, R H;Daringer, N M;Davanloo, P;Davis, K M;De Munter, S;Dicarlo, J E;Dixon, A S;Domin, G;Dong, S Y;Doudna, J A;Duan, F P;Dupin, A;Durniak, K J;Eggeling, L;Ellington, A D;Esvelt, K M;Farzadfard, F;Feng, J;Fernandez-Rodriguez, J;Fink, T;Fischbach, M A;Fowler, C C;Friedland, A E;Friedlos, F;Fu, Y F;Galarneau, A;Gangopadhyay, S A;Gao, X J;Gao, Y C;Gardner, T S;Ghosh, I;Gilbert, L A;Golynskiy, M V;Gratz, S J;Gray, D C;Green, O;Gruber, T D;Guntas, G;Han, T Y;Han, Y S;Hartfield, R M;Hattori, M;Hombach, A;Horvath, P;Hu, J H;Hwang, I Y;Hwang, W Y;Hynes, A P;Ikeda, R A;Imburgio, D;Iost, I;Isabella, V M;Jester, B W;Jiang, W Z;Jinek, M;Jones, K A;Jusiak, B;Justino, C I L;Juárez, J F;Kaczmarski, J A;Kenyon, C J;Kiani, S;Kim, C K;Kirsch, J;Kitada, T;Kleinstiver, B P;Kobayashi, H;Kodama, Y;Konermann, S;Kotula, J W;Kroeze, W K;Landowski, C P;Lanitis, E;Lavis, L D;Lee, H L;Lee, J;Lee, J F;Li, D T;Liang, F S;Liang, J C;Liang, P P;Lienert, F;Lin, Y N;Lippert, A R;Litcofsky, K D;Liu, Y C;Lutz, R;Lynch, S A;Ma, D C;Ma, Q Z;Machtel, P;Maeder, M L;Mahr, R;Maji, B;Marchesi, J R;Martell, J D;Mccormack, E;Mcguinness, R P;Meyer, A J;Michnick, S W;Mimee, M;Mishra, G K;Morsut, L;Muller, D K;Müller, S;Naydich, A D;Nguyen, D P;Niederholtmeyer, H;Nihongaki, Y;Nishimasu, H;Nissim, L;Niu, Y Y;Nolan, K F;Nuñez, J K;Oakes, B L;Ogawa, A;Ozawa, T;Pawluk, A;Peng, J;Perez-Pinera, P;Phelan, R M;Polstein, L R;Porterfield, W B;Pu, J Y;Puton, T;Raina, M;Rauch, B J;Rauch, S;Redfern, C H;Rehberg, M;Riglar, D T;Rogers, J K;Ronda, C;Roybal, K T;Schaerli, Y;Scheller, L;Schmelas, C;Schmidt, C M;Schopp, I M;Schwarz, K A;Segall-Shapiro, T H;Senturk, S;Sharma, V;Shaver Zachary, M;Shcherbakova, D M;Shekhawat, S S;Sheth, R U;Shi, S;Shin, J;Shis, D L;Shyu, Y J;Siuti, P;Slomovic, S;Sousa, R;Stano, N M;Steidler, L;Steitz, T A;Sternson, S M;Strader, C D;Studier, F W;Tahirov, T H;Temiakov, D;Temme, K;Terns, M P;Thodima, V;Tian, L;Toda, S;Townshend, B;Truong, D J J;Tuerk, C;Turner, A P F;Vandenbroucke, K;Varankovich, N V;Vorobyeva, A G;Wade, M;Wang, B J;Wang, D;Wang, H Y;Wang, J;Wang, M;Wang, T N;Wang, W Y;Way, J C;Wehr, M C;Westwood, J A;Whitaker, W R;Wierdl, M;Wintgens, J P;Wittmann, A;Wright, A V;Xie, H H;Xiu, Y;Xu, X S;Yang, Y P;Yin, Y W;Yoshimi, K;Yu, Y;Zhang, J
KQ9SA
Chicago, IL USA
9
null
1
null
null
Dickinson, Bryan C;Jones, Krysten A;Zinkus-Boltz, Julia
NANO FUTURES
Chicago, IL USA
Nakanishi, H;Saito, H
10.1016/j.cbpa.2019.04.013
null
THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
4v1dh303h481x4h4d4182r5w60y3v4b105r45
Mammalian gene circuits with biomolecule-responsive RNA devices
Kyoto Univ
null
Saito, H (corresponding author), Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan.
null
Nakanishi, Hideyuki;Saito, Hirohide
Biochemistry & Molecular Biology;Biophysics
Japan Society for the Promotion of Science (JSPS) KAKENHI [15H05722]
WOS
Saito, H
Kyoto Univ, Kyoto, Japan
52
biomolecule-responsive;circuits;devices;gene;mammalian;RNA;with
1
Nakanishi, Hideyuki
ELSEVIER SCI LTD
Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan
Review
Kyoto Univ
OXFORD
null
null
Kyoto Univ
Japan Society for the Promotion of Science (JSPS) KAKENHI
Saito, H (corresponding author), Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan.
22
Nakanishi, Hideyuki;Saito, Hirohide
17
1
496,872,800,005
Japan Society for the Promotion of Science (JSPS) KAKENHI [15H05722]
Japan
CURRENT OPINION IN CHEMICAL BIOLOGY
Japan
null
null
Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan
1367-5931
Nakanishi, H;Saito, H
OCT
hirohide.saito@cira.kyoto-u.ac.jp
biomolecule-responsive RNA devices;mammalian gene circuits
2
J
Biochemistry & Molecular Biology;Biophysics
another RNA device;autonomous cellular state-dependent regulation;biological studies;biomolecule-responsive mammalian gene circuits;biomolecule-responsive RNA devices;cell specific gene regulation;cells;CIRCUITS;components;input;insertional mutagenesis;killing;layered gene circuits;LIN28;low risk;mammalian gene circuits;mammalian synthetic gene circuits;one RNA device;output;recent advancements;review;RNA devices;sophisticated regulation;synthetic biologists;target cell population;therapeutic applications;tools
Nakanishi, H
CELLS;LIN28
16
[Nakanishi, Hideyuki; Saito, Hirohide] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan.
We thank Dr Peter Karagiannis (Kyoto University) for English proofreading. This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI No. 15H05722.
another RNA device;autonomous cellular state-dependent regulation;biological studies;biomolecule-responsive mammalian gene circuits;biomolecule-responsive RNA devices;cell specific gene regulation;circuits;components;input;insertional mutagenesis;killing;layered gene circuits;low risk;mammalian synthetic gene circuits;one RNA device;output;recent advancements;review;RNA devices;sophisticated regulation;synthetic biologists;target cell population;therapeutic applications;tools
10.1016/j.biomaterials.2017.02.033;10.1016/j.humpath.2010.09.007;10.1016/j.stem.2015.04.005;10.1016/j.ymthe.2018.02.021;10.1021/sb200005w;10.1038/nbt.3301;10.1038/ncomms1157;10.1038/ncomms3393;10.1038/s41467-017-00459-x;10.1038/s41467-018-06825-7;10.1038/s41467-018-07181-2;10.1038/s41589-018-0146-9;10.1038/sj.cgt.7700752;10.1038/sj.gt.3301602;10.1038/srep21991;10.1038/srep32532;10.1093/nar/gks668;10.1093/nar/gkx309;10.1096/fj.201600848R;10.1097/PAS.0b013e31802e708a;10.1128/JVI.79.12.7597-7608.2005;[10.1038/NCHEMBIO.273, 10.1038/nchembio.273]
Kyoto Univ
Nakanishi, H;Saito, H
Nakanishi, H: Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan
Nakanishi, Hideyuki
15H05722
25
null
Japan
Kyoto Univ
Nakanishi, Hideyuki
null
CELLS;LIN28
Nakanishi, Hideyuki; Saito, Hirohide;
null
Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan
Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan
1879-0402
null
null
2001;2004;2005;2007;2010;2011;2012;2013;2015;2016;2017;2018
8
Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan
Curr. Opin. Chem. Biol.
Saito, Hirohide
ELSEVIER SCI LTD
,;a;addition;advancements;and;another;applications;are;as;autonomous;based;be;because;biological;biologists;biomolecule-responsive;both;can;cell;cellular;circuits;components;construct;device;devices;enable;explain;for;gene;in;input;insertional;killing;layered;low;mammalian;more;mutagenesis;of;on;one;output;population;preferred;promising;recent;regulation;review;risk;RNA;sophisticated;specific;state-dependent;studies;such;synthetic;target;the;therapeutic;these;they;this;tools;we;with
Kyoto Univ
Mammalian synthetic gene circuits are promising tools for both biological studies and therapeutic applications. These circuits enable autonomous cellular state-dependent regulation such as the killing of a target cell population. Biomolecule-responsive RNA devices are preferred components of mammalian synthetic gene circuits, because they enable cell specific gene regulation with a low risk of insertional mutagenesis. In addition, because the output of one RNA device can be the input of another RNA device, synthetic biologists can construct layered gene circuits for more sophisticated regulation. In this review, we explain recent advancements of biomolecule-responsive mammalian gene circuits based on RNA devices.
Q-5855-2017
CELLS;LIN28
1
null
null
7
CELLS;LIN28
WOS:000496872800005
Kyoto Univ, Kyoto, Japan
Japan
2,019
null
0000-0003-1159-3676
null
null
English
null
ACS SYNTH BIOL;AM J SURG PATHOL;BIOMATERIALS;CANCER GENE THER;CELL STEM CELL;FASEB J;GENE THER;HUM PATHOL;J VIROL;MOL THER;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NUCLEIC ACIDS RES;SCI REP;SCI REP-UK
Nakanishi, Hideyuki;Saito, Hirohide
2024-03-11 ER
Cao, D F;Cella, F;Chen, J S;Endo, K;Hirosawa, M;Kashida, S;Kawasaki, S;Matsuura, S;Miki, K;Mou, H H;Nakanishi, H;Parisi, S;Parr, C J C;Petrakova, O;Saito, H;Sano, M;Santagata, S;Shibata, T;Stapleton, J A;Wagner, T E;Weeratna, R D;Wroblewska, L
JN4MH
Kyoto, Japan
9
null
1
null
31,129,468
Nakanishi, Hideyuki;Saito, Hirohide
CURR OPIN CHEM BIOL
Kyoto, Japan
de Greef, T F A;Huck, W T S;Maerkl, S J;Pieters, P;Swank, Z;van der Linden, A J;Yelleswarapu, M
10.3791/59655
e59655
1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
3s1s1ym1o2t5g53x2m32k3u3i31175b3cdc
A Multilayer Microfluidic Platform for the Conduction of Prolonged Cell-Free Gene Expression
Eindhoven Univ Technol
null
de Greef, TFA (corresponding author), Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands.;de Greef, TFA (corresponding author), Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands.;Maerkl, SJ (corresponding author), Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lausanne, Switzerland.
null
de Greef, Tom F A;Huck, Wilhelm T S;Maerkl, Sebastian J;Pieters, Pascal;Swank, Zoe;van der Linden, Ardjan J;Yelleswarapu, Maaruthy
Multidisciplinary Sciences
European Research Council, ERC [677313 BioCircuit]; NWO-VIDI grant from the Netherlands Organization for Scientific Research (NWO) [723.016.003]; Ministry of Education, Culture and Science [024.001.035, 024.003.013]; Human Frontier Science Program [RGP0032/2015]; European Research Council under the European Union [723106]; Swiss National Science Foundation [200021_182019]; Swiss National Science Foundation (SNF) [200021_182019] Funding Source: Swiss National Science Foundation (SNF); European Research Council (ERC) [723106] Funding Source: European Research Council (ERC)
WOS
de Greef, T F A;Maerkl, S J
Ecole Polytech Fed Lausanne, Lausanne, Switzerland;Eindhoven Univ Technol, Eindhoven, Netherlands;Radboud Univ Nijmegen, Nijmegen, Netherlands
null
a;Cell-Free;Conduction;expression;for;gene;Microfluidic;Multilayer;of;Platform;Prolonged;the
2
Maerkl, Sebastian J.
JOURNAL OF VISUALIZED EXPERIMENTS
Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lausanne, Switzerland;Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands;Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands.; de Greef, TFA (corresponding author), Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands.; Maerkl, SJ (corresponding author), Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lausanne, Switzerland;Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands
Article
Ecole Polytech Fed Lausanne;Eindhoven Univ Technol;Radboud Univ Nijmegen
CAMBRIDGE
null
null
Ecole Polytech Fed Lausanne;Eindhoven Univ Technol;Radboud Univ Nijmegen
European Research Council (ERC);European Research Council under the European Union;European Research Council, ERC;Human Frontier Science Program;Ministry of Education, Culture and Science;NWO-VIDI grant from the Netherlands Organization for Scientific Research (NWO);Swiss National Science Foundation;Swiss National Science Foundation (SNF)
de Greef, TFA (corresponding author), Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands.; de Greef, TFA (corresponding author), Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands.; Maerkl, SJ (corresponding author), Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lausanne, Switzerland.
null
de Greef, Tom F A;Huck, Wilhelm T S;Maerkl, Sebastian J;Pieters, Pascal;Swank, Zoe;van der Linden, Ardjan J;Yelleswarapu, Maaruthy
9
3
493,379,500,013
European Research Council (ERC) [723106] Funding Source: European Research Council (ERC);European Research Council under the European Union [723106];European Research Council, ERC [677313 BioCircuit];Human Frontier Science Program [RGP0032/2015];Ministry of Education, Culture and Science [024.001.035, 024.003.013];NWO-VIDI grant from the Netherlands Organization for Scientific Research (NWO) [723.016.003];Swiss National Science Foundation (SNF) [200021_182019] Funding Source: Swiss National Science Foundation (SNF);Swiss National Science Foundation [200021_182019]
Netherlands;Switzerland
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
Netherlands;Switzerland
null
null
Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands
1940-087X
de Greef, T F A;Huck, W T S;Maerkl, S J;Pieters, P;Swank, Z;van der Linden, A J;Yelleswarapu, M
OCT
sebastian.maerkl@epfl.ch;t.f.a.d.greef@tue.nl
Conduction;Multilayer Microfluidic Platform;Prolonged Cell-Free Gene Expression
7
J
Science & Technology - Other Topics
(by-) products;analysis;Bioengineering;cell-based synthetic biology;cell-free characterization;cellular environment;cellular processes;combining IVTT reactions;complex network behaviors;complex synthetic genetic regulatory circuits;Conduction;CONSTRUCTION;CONTEXT;contrast;dynamic behavior;environmental control;exogenous synthetic components;experimental environment;extended periods;Fabrication;FREE PROTEIN-SYNTHESIS;Gene circuits;hardware;host processes;in vitro transcription and translation;Issue 152;issues;IVTT reactions;lack;limitations;mechanisms;micro-reactors;microfluidic devices;microfluidic platform;MICROFLUIDICS;multilayer microfluidic device;Multilayer Microfluidic Platform;networks;novel circuitry;out-of-equilibrium environment;prevalent;Prolonged Cell-Free Gene Expression;prolonged durations;prolonged reactions;PROTEIN EXPRESSION;protocols;reaction products;reactions;regulation;removal;replenishment;researchers aim;resources;software;synthetic biology;synthetic genetic regulatory networks;time;translation (IVTT) mixtures;understanding;undesired behavior;unique system;use;vitro transcription;vivo
van der Linden, A J
Bioengineering;CONSTRUCTION;CONTEXT;FREE PROTEIN-SYNTHESIS;in vitro transcription and translation;Issue 152;micro-reactors;MICROFLUIDICS;NETWORKS;prolonged reactions;PROTEIN EXPRESSION;Synthetic biology
null
[van der Linden, Ardjan J.; Pieters, Pascal; de Greef, Tom F. A.] Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands. [Yelleswarapu, Maaruthy; Huck, Wilhelm T. S.; de Greef, Tom F. A.] Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands. [Swank, Zoe; Maerkl, Sebastian J.] Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lausanne, Switzerland.
This work was supported by the European Research Council, ERC (project n. 677313 BioCircuit) an NWO-VIDI grant from the Netherlands Organization for Scientific Research (NWO, 723.016.003), funding from the Ministry of Education, Culture and Science (Gravity programs, 024.001.035 & 024.003.013), the Human Frontier Science Program Grant RGP0032/2015, the European Research Council under the European Union's Horizon 2020 research and innovation program Grant 723106, and a Swiss National Science Foundation Grant 200021_182019.
(by-) products;analysis;cell-based synthetic biology;cell-free characterization;cellular environment;cellular processes;combining IVTT reactions;complex network behaviors;complex synthetic genetic regulatory circuits;contrast;dynamic behavior;environmental control;exogenous synthetic components;experimental environment;extended periods;fabrication;gene circuits;hardware;host processes;issues;IVTT reactions;lack;limitations;mechanisms;microfluidic devices;microfluidic platform;multilayer microfluidic device;novel circuitry;out-of-equilibrium environment;prevalent;prolonged durations;protocols;reaction products;reactions;regulation;removal;replenishment;researchers aim;resources;software;synthetic genetic regulatory networks;time;translation (IVTT) mixtures;understanding;undesired behavior;unique system;use;vitro transcription;vivo
10.1002/biot.201200085;10.1002/smll.201502764;10.1006/bbrc.1999.0404;10.1016/j.biotechadv.2013.04.008;10.1016/j.cbpa.2012.05.179;10.1016/j.mib.2016.07.009;10.1016/j.molcel.2016.06.006;10.1016/j.ohx.2017.10.001;10.1016/j.ohx.2017.10.002;10.1016/j.tibtech.2014.11.009;10.1016/j.ymeth.2015.05.020;10.1021/acssynbio.5b00090;10.1021/acssynbio.5b00296;10.1021/sb200016s;10.1021/sb400131a;10.1038/35002125;10.1038/35002131;10.1038/90802;10.1038/nature04473;10.1038/ncomms15128;10.1038/nrg2775;10.1038/nrm2698;10.1039/b808034h;10.1039/c1lc20462a;10.1039/c2lc40649g;10.1039/c5cs00361j;10.1039/c5lc00700c;10.1039/c6lc00367b;10.1073/pnas.1212069109;10.1073/pnas.1311166110;10.1073/pnas.2135496100;10.1093/nar/gkr1191;10.1101/cshperspect.a023812;10.1109/ACC.2007.4282302;10.1126/science.1151721;10.1126/science.1192588;10.1126/science.1255550;10.1126/science.288.5463.113;10.1126/science.3055301;10.1371/journal.pone.0073015;10.7554/eLife.09771
Eindhoven Univ Technol
de Greef, T F A;Huck, W T S;Maerkl, S J;Pieters, P;Swank, Z;van der Linden, A J;Yelleswarapu, M
van der Linden, A J: Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands
de Greef, Tom F. A.;Huck, Wilhelm T.S.;Maerkl, Sebastian J. J
024.001.035;024.003.013;200021_182019;677313 BioCircuit;723.016.003;723106;RGP0032/2015
49
null
Netherlands
Ecole Polytech Fed Lausanne;Eindhoven Univ Technol;Radboud Univ Nijmegen
van der Linden, Ardjan J
Green Published, Bronze, Green Submitted
CONSTRUCTION;CONTEXT;FREE PROTEIN-SYNTHESIS;NETWORKS;SYNTHETIC BIOLOGY
van der Linden, Ardjan J.; Yelleswarapu, Maaruthy; Pieters, Pascal; Swank, Zoe; Huck, Wilhelm T. S.; Maerkl, Sebastian J.; de Greef, Tom F. A.;
null
Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lausanne, Switzerland;Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands;Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands
Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lausanne, Switzerland;Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands;Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands
null
Bioengineering;in vitro transcription and translation;Issue 152;micro-reactors;Microfluidics;prolonged reactions;protein expression;Synthetic biology
152
1988;1999;2000;2001;2003;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
7
Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lausanne, Switzerland;Eindhoven Univ Technol, Dept Biomed Engn, Computat Biol Grp, Inst Complex Mol Syst, Eindhoven, Netherlands;Radboud Univ Nijmegen, Inst Mol & Mat, Nijmegen, Netherlands
J. Vis. Exp.
de Greef, Tom F A
JOURNAL OF VISUALIZED EXPERIMENTS
(by-);(IVTT);,;a;accumulate;aim;allow;allows;an;analysis;analyze;and;apparent;are;as;automate;batch;be;becomes;becoming;been;behavior;behaviors;biology;by;can;cell-based;cell-free;cellular;characterization;circuitry;circuits;combining;complex;components;comprehensively;consuming;contrast;control;depleted;detail;develop;device;devices;durations;dynamic;each;emulated;environment;environmental;exogenous;experimental;exploit;extended;fabrication;for;from;fully;furthering;gene;genetic;hardware;have;here;host;in;increasingly;integrated;interacting;investigated;is;issues;it;IVTT;lack;larger;limitations;maintaining;manner;mechanisms;microfluidic;mixtures;more;multilayer;network;networks;novel;of;optimized;our;out-of-equilibrium;over;overcome;periods;platform;possible;presented;prevalent;processes;products;prolonged;protocols;reaction;reactions;regulate;regulation;regulatory;removal;replenishment;researchers;resources;resulting;software;suffers;sustain;synthetic;system;that;the;these;this;time;to;transcription;translation;understanding;undesired;unique;use;utilized;vitro;vivo;well;where;which;with
Ecole Polytech Fed Lausanne;Eindhoven Univ Technol;Radboud Univ Nijmegen
The limitations of cell-based synthetic biology are becoming increasingly apparent as researchers aim to develop larger and more complex synthetic genetic regulatory circuits. The analysis of synthetic genetic regulatory networks in vivo is time consuming and suffers from a lack of environmental control, with exogenous synthetic components interacting with host processes resulting in undesired behavior. To overcome these issues, cell-free characterization of novel circuitry is becoming more prevalent. In vitro transcription and translation (IVTT) mixtures allow the regulation of the experimental environment and can be optimized for each unique system. The protocols presented here detail the fabrication of a multilayer microfluidic device that can be utilized to sustain IVTT reactions for prolonged durations. In contrast to batch reactions, where resources are depleted over time and (by-) products accumulate, the use of microfluidic devices allows the replenishment of resources as well as the removal of reaction products. In this manner, the cellular environment is emulated by maintaining an out-of-equilibrium environment in which the dynamic behavior of gene circuits can be investigated over extended periods of time. To fully exploit the multilayer microfluidic device, hardware and software have been integrated to automate the IVTT reactions. By combining IVTT reactions with the microfluidic platform presented here, it becomes possible to comprehensively analyze complex network behaviors, furthering our understanding of the mechanisms that regulate cellular processes.
B-1471-2012;C-5438-2008;I-8124-2014
CONSTRUCTION;CONTEXT;FREE PROTEIN-SYNTHESIS;NETWORKS;SYNTHETIC BIOLOGY
0
null
Bioengineering;in vitro transcription and translation;Issue 152;micro-reactors;Microfluidics;prolonged reactions;protein expression;Synthetic biology
14
Bioengineering;CONSTRUCTION;CONTEXT;FREE PROTEIN-SYNTHESIS;in vitro transcription and translation;Issue 152;micro-reactors;MICROFLUIDICS;NETWORKS;prolonged reactions;PROTEIN EXPRESSION;Synthetic biology
WOS:000493379500013
Ecole Polytech Fed Lausanne, Lausanne, Switzerland;Eindhoven Univ Technol, Eindhoven, Netherlands;Radboud Univ Nijmegen, Nijmegen, Netherlands
Netherlands;Switzerland
2,019
null
0000-0003-1917-5268
null
null
English
null
2007 American Control Conference;ACS SYNTH BIOL;ACSYNTHETIC BIOL;BIOCHEM BIOPH RES CO;BIOTECHNOL ADV;BIOTECHNOL J;BIOTECHNOLOGY BIOENG;CHEM SOC REV;CSH PERSPECT BIOL;CURR OPIN CHEM BIOL;CURR OPIN MICROBIOL;ELIFE;HARDWAREX;J VAC SCI TECHNOL B;LAB CHIP;METHODS;MOL CELL;MOL SYSTEMS BIOL;NAT BIOTECHNOL;NAT COMMUN;NAT REV GENET;NAT REV MOL CELL BIO;NATURE;NATURE MICROBIOLOGY;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;SCI REPORTS;SCIENCE;SMALL;TRENDS BIOTECHNOL
de Greef, Tom F A;Huck, Wilhelm T S;Maerkl, Sebastian J;Pieters, Pascal;Swank, Zoe;van der Linden, Ardjan J;Yelleswarapu, Maaruthy
2024-03-11 ER
Borkowski, O;Brower, K;Cardinale, S;De Los Santos, E L C;Del Vecchio D.;Del Vecchio, D;Doktycz M. J.;Dunlop M., J;Elowitz, M B;Galas, J C;Garamella, J;Gardner, T S;Genot, A J;Georgi, V;Gibson, D G;Guido, N J;Guo, S;Hockenberry, A J;Hughes, R A;Iyer, S;Kaminski, T S;Kantak C.;Karig, D K;Karzbrun, E;Khalil, A S;Khnouf, R;Lee, J W;Liao C.;Montagne K.;Niederholtmeyer, H;Noireaux, V;Oberholzer, T;Padirac, A;Purnick, P E M;Scott, M;Shimizu, Y;Shin, J;Siuti, P;Spirin, A S;Sun, Z Z;Takahashi, M K;Timm, A C;Unger, M A;Van Roekel, H W H;Venturelli, O S;White, J A;Yelleswarapu, M;Yoshiyama T.
JI3PV
Eindhoven, Netherlands.;Lausanne, Switzerland;Nijmegen, Netherlands.
8
null
3
null
31,633,684
de Greef, Tom F A;Huck, Wilhelm T S;Maerkl, Sebastian J;Pieters, Pascal;Swank, Zoe;van der Linden, Ardjan J;Yelleswarapu, Maaruthy
JOVE-J VIS EXP
Eindhoven, Netherlands;Lausanne, Switzerland;Nijmegen, Netherlands
Graham, D;Jun, T;Lu, T K;Müller, I E;Rubens, J R;Xavier, R
10.1038/s41467-019-12021-y
4028
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
5s640a1k66m5n3z6kg2gf6h395p5f6x5do
Gene networks that compensate for crosstalk with crosstalk
MIT
null
Lu, TK (corresponding author), MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA.;Lu, TK (corresponding author), MIT, Microbiol Program, Cambridge, MA 02139 USA.
null
Graham, Daniel;Jun, Tomi;Lu, Timothy K;Mueller, Isaak E;Rubens, Jacob R;Xavier, Ramnik
Multidisciplinary Sciences
NSF Graduate Research Fellowship; National Science Foundation [1350625, 1124247]; Office of Naval Research [N000141310424]; NIH New Innovator Award [1DP2OD008435]; NIH National Centers for Systems Biology [1P50GM098792]; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1350625] Funding Source: National Science Foundation; Division of Computing and Communication Foundations; Direct For Computer & Info Scie & Enginr [1124247] Funding Source: National Science Foundation
WOS
Lu, T K
Broad Inst, Cambridge, MA USA;Harvard MIT Hlth Sci & Technol Program, Cambridge, MA USA;Massachusetts Gen Hosp, Boston, MA USA;MIT, Cambridge, MA USA;Mt Sinai Hosp, New York, NY USA
10
compensate;crosstalk;for;gene;networks;that;with
1
Jun, Tomi
NATURE PUBLISHING GROUP
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA;Harvard MIT Hlth Sci & Technol Program, Cambridge, MA 02139 USA;Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA;Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA;Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA;MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA;MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Microbiol Program, Cambridge, MA 02139 USA;MIT, Microbiol Program, Cambridge, MA 02139 USA;Mt Sinai Hosp, Div Hematol & Med Oncol, New York, NY 10029 USA
Article
MIT
LONDON
null
null
Broad Inst;Dept Elect Engn & Comp Sci;Harvard MIT Hlth Sci & Technol Program;Massachusetts Gen Hosp;MIT;Mt Sinai Hosp
Direct For Biological Sciences;Direct For Computer & Info Scie & Enginr;Div Of Molecular and Cellular Bioscience;Division of Computing and Communication Foundations;National Science Foundation;NIH National Centers for Systems Biology;NIH New Innovator Award;NSF Graduate Research Fellowship;Office of Naval Research
Lu, TK (corresponding author), MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Microbiol Program, Cambridge, MA 02139 USA.
null
Graham, Daniel;Jun, Tomi;Lu, Timothy K;Mueller, Isaak E;Rubens, Jacob R;Xavier, Ramnik
21
8
484,596,900,008
Direct For Biological Sciences;Direct For Computer & Info Scie & Enginr [1124247] Funding Source: National Science Foundation;Div Of Molecular and Cellular Bioscience [1350625] Funding Source: National Science Foundation;Division of Computing and Communication Foundations;National Science Foundation [1350625, 1124247];NIH National Centers for Systems Biology [1P50GM098792];NIH New Innovator Award [1DP2OD008435];NSF Graduate Research Fellowship;Office of Naval Research [N000141310424]
USA
NATURE COMMUNICATIONS
USA;USA.;
null
null
MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA
2041-1723
Graham, D;Jun, T;Lu, T K;Müller, I E;Rubens, J R;Xavier, R
SEP 6
timlu@mit.edu
crosstalk;gene
6
J
Science & Technology - Other Topics
biological networks;COMBINATORIAL;common approach;compensatory crosstalk;crosstalk;degree;DESIGN;design gene;engineering sophisticated synthetic gene networks;environmental signals;Escherichia coli;ESCHERICHIA-COLI;evolution;exhibit concentration-dependent crosstalk;GENE;gene network level;HYDROGEN-PEROXIDE;integrating pathway signals;major challenge;molecular-level crosstalk;natural gene networks;non-cognate ROS;pathway crosstalk;pathway insulation;principle;reactive oxygen species (ROS)-responsive gene circuits;regulatory networks;resulting gene network exhibits reduced crosstalk;results;sensing;signal-transduction pathways;simple network motifs;SOXR PROTEIN;specificity;strategy;synthetic gene networks;synthetic genetic components;TALK;two different ROS;unknown interactions;yeast
Müller, I E
COMBINATORIAL;DESIGN;ESCHERICHIA-COLI;EVOLUTION;HYDROGEN-PEROXIDE;REGULATORY NETWORKS;SOXR PROTEIN;SPECIFICITY;TALK;YEAST
null
[Mueller, Isaak E.; Rubens, Jacob R.; Jun, Tomi; Lu, Timothy K.] MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA. [Mueller, Isaak E.; Rubens, Jacob R.; Lu, Timothy K.] MIT, Microbiol Program, Cambridge, MA 02139 USA. [Jun, Tomi] Harvard MIT Hlth Sci & Technol Program, Cambridge, MA 02139 USA. [Graham, Daniel; Xavier, Ramnik] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Graham, Daniel; Xavier, Ramnik] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Graham, Daniel; Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Jun, Tomi] Mt Sinai Hosp, Div Hematol & Med Oncol, New York, NY 10029 USA.
We would like to thank members of the Lu Lab, the MIT Microbiology Program, and the MIT Synthetic Biology Center for their feedback. We thank the staff at the Koch Institute Flow Cytometry Core for their assistance in flow cytometry. J.R.R. was supported by an NSF Graduate Research Fellowship. This work was supported by the National Science Foundation (#1350625 and #1124247) and the Office of Naval Research (#N000141310424), an NIH New Innovator Award (#1DP2OD008435), and the NIH National Centers for Systems Biology (#1P50GM098792).
biological networks;common approach;compensatory crosstalk;crosstalk;degree;design gene;engineering sophisticated synthetic gene networks;environmental signals;Escherichia coli;exhibit concentration-dependent crosstalk;gene network level;integrating pathway signals;major challenge;molecular-level crosstalk;natural gene networks;non-cognate ROS;pathway crosstalk;pathway insulation;principle;reactive oxygen species (ROS)-responsive gene circuits;resulting gene network exhibits reduced crosstalk;results;sensing;signal-transduction pathways;simple network motifs;strategy;synthetic gene networks;synthetic genetic components;two different ROS;unknown interactions
10.1002/biot.201100487;10.1016/j.cell.2009.01.055;10.1016/j.cell.2012.05.033;10.1016/j.cell.2014.02.033;10.1016/j.cell.2014.04.047;10.1016/j.chembiol.2014.10.008;10.1016/j.cub.2008.07.050;10.1016/j.devcel.2011.11.006;10.1016/j.mib.2010.09.001;10.1016/j.tibs.2011.03.006;10.1021/sb300030d;10.1021/sb300084h;10.1038/463288a;10.1038/cr.2008.302;10.1038/msb.2013.58;10.1038/msb4100050;10.1038/msb4100135;10.1038/msb4100187;10.1038/nature02178;10.1038/nature06347;10.1038/nature11149;10.1038/nature11259;10.1038/nature11516;10.1038/nature12148;10.1038/nature13582;10.1038/nbt.1536;10.1038/nbt.1617;10.1038/nbt1209;10.1038/nbt731;10.1038/ncomms11658;10.1038/ncomms2471;10.1038/ng881;10.1038/nmeth.2884;10.1038/nrg3227;10.1038/nrmicro3032;10.1038/nrmicro3238;10.1073/pnas.0403350102;10.1073/pnas.0608451104;10.1073/pnas.1312414110;10.1073/pnas.1317178111;10.1073/pnas.1418058112;10.1074/jbc.M110715200;10.1074/jbc.M112.395079;10.1093/emboj/17.9.2629;10.1093/nar/25.6.1203;10.1093/nar/gkq810;10.1093/nar/gkt452;10.1101/gad.1700308;10.1111/j.1365-2958.2008.06426.x;10.1111/j.1365-2958.2010.07520.x;10.1126/science.1075090;10.1126/science.1192588;10.1126/science.1207084;10.1126/science.1256272;10.1126/science.271.5251.990;10.1126/scitranslmed.3005568;10.1128/AEM.00791-07;10.1128/AEM.62.7.2252-2256.1996;10.1146/annurev-micro-092611-150039;10.1146/annurev.genet.41.042007.170548;10.1186/1752-0509-5-111;10.1186/1754-1611-5-12;10.1186/1754-1611-8-2;10.1371/journal.pbio.0030334;10.1371/journal.pone.0011909;10.1371/journal.pone.0016136;10.7554/eLife.00669
MIT
Graham, D;Jun, T;Lu, T K;Müller, I E;Rubens, J R;Xavier, R
Müller, I E: MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA
Jun, Tomi;Lu, Timothy K
1124247;1350625;1DP2OD008435;1P50GM098792;N000141310424
69
null
USA
Broad Inst;Harvard MIT Hlth Sci & Technol Program;Massachusetts Gen Hosp;MIT;Mt Sinai Hosp
Mueller, Isaak E
Green Published, gold
COMBINATORIAL;DESIGN;ESCHERICHIA-COLI;EVOLUTION;HYDROGEN-PEROXIDE;REGULATORY NETWORKS;SOXR PROTEIN;SPECIFICITY;TALK;YEAST
Mueller, Isaak E.; Rubens, Jacob R.; Jun, Tomi; Graham, Daniel; Xavier, Ramnik; Lu, Timothy K.;
null
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA;Harvard MIT Hlth Sci & Technol Program, Cambridge, MA 02139 USA;Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA;Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA;Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA;MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA;MIT, Microbiol Program, Cambridge, MA 02139 USA;Mt Sinai Hosp, Div Hematol & Med Oncol, New York, NY 10029 USA
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA;Harvard MIT Hlth Sci & Technol Program, Cambridge, MA 02139 USA;Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA;Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA;Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA;MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA;MIT, Microbiol Program, Cambridge, MA 02139 USA;Mt Sinai Hosp, Div Hematol & Med Oncol, New York, NY 10029 USA
null
null
null
1991;1996;1997;1998;1999;2002;2003;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016
21
MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Synthet Biol Grp,Synthet Biol Ctr, Cambridge, MA 02139 USA;MIT, Microbiol Program, Cambridge, MA 02139 USA
Nat. Commun.
Lu, Timothy K
NATURE PUBLISHING GROUP
(ROS)-responsive;,;a;accurately;and;apply;approach;at;be;between;biological;but;by;can;challenge;circuits;coli;common;compensate;compensatory;complex;components;concentration-dependent;context;crosstalk;degree;demonstrate;design;different;difficult;endogenous;engineered;engineering;environmental;Escherichia;exhibit;exhibits;for;gene;genetic;here;in;insulate;insulation;integrating;interactions;interpret;introduce;is;level;major;map;minimizing;molecular-level;motifs;natural;network;networks;non-cognate;of;our;oxygen;pathway;pathways;principle;quantitatively;rather;reactive;reduced;resulting;results;ROS;sensing;show;signal-transduction;signals;simple;sophisticated;species;strategy;suggest;synthetic;than;that;the;this;to;two;unknown;used;using;we;with
MIT
Crosstalk is a major challenge to engineering sophisticated synthetic gene networks. A common approach is to insulate signal-transduction pathways by minimizing molecular-level crosstalk between endogenous and synthetic genetic components, but this strategy can be difficult to apply in the context of complex, natural gene networks and unknown interactions. Here, we show that synthetic gene networks can be engineered to compensate for crosstalk by integrating pathway signals, rather than by pathway insulation. We demonstrate this principle using reactive oxygen species (ROS)-responsive gene circuits in Escherichia coli that exhibit concentration-dependent crosstalk with non-cognate ROS. We quantitatively map the degree of crosstalk and design gene circuits that introduce compensatory crosstalk at the gene network level. The resulting gene network exhibits reduced crosstalk in the sensing of the two different ROS. Our results suggest that simple network motifs that compensate for pathway crosstalk can be used by biological networks to accurately interpret environmental signals.
AAJ-4152-2020;G-4267-2012
COMBINATORIAL;DESIGN;ESCHERICHIA-COLI;EVOLUTION;HYDROGEN-PEROXIDE;REGULATORY NETWORKS;SOXR PROTEIN;SPECIFICITY;TALK;YEAST
0
null
null
8
ESCHERICHIA-COLI;YEAST;COMBINATORIAL;DESIGN;EVOLUTION;HYDROGEN-PEROXIDE;REGULATORY NETWORKS;SOXR PROTEIN;SPECIFICITY;TALK
WOS:000484596900008
Broad Inst, Cambridge, MA USA;Harvard MIT Hlth Sci & Technol Program, Cambridge, MA USA;Massachusetts Gen Hosp, Boston, MA USA;MIT, Cambridge, MA USA;Mt Sinai Hosp, New York, NY USA
USA
2,019
null
0000-0002-2120-1704
null
null
English
null
ACS SYNTH BIOL;ANNU REV GENET;ANNU REV MICROBIOL;APPL ENVIRON MICROB;BIOTECHNOL J;BMC SYST BIOL;CELL;CELL RES;CHEM BIOL;CURR BIOL;CURR OPIN MICROBIOL;DEV CELL;ELIFE;EMBO J;GENE DEV;J BACTERIOL;J BIOCHEM-TOKYO;J BIOL CHEM;J Biol Eng;MOL MICROBIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT COMMUN;NAT GENET;NAT METHODS;NAT REV GENET;NAT REV MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS BIOL;PLOS ONE;SCI TRANSL MED;SCIENCE;TRENDS BIOCHEM SCI
Graham, Daniel;Jun, Tomi;Lu, Timothy K;Mueller, Isaak E;Rubens, Jacob R;Xavier, Ramnik
2024-03-11 ER
Ausländer, S;Baba, T;Beal, J;Belkin, S;Cai, S J;Cantone, I;Capra, E J;Chubukov, V;Collins, C H;Cox, R S;Daniel, R;Davis, J H;Dessaud, E;Dwyer, D J;Ellis, T;Escalante-Chong, R;Farzadfard, F;Fischbach, M A;Fujikawa, M;González-Flecha, B;Gu, M Z;Guo, X;Hidalgo, E;Imlay, J A;Keiler, K C;Kemmer, C;Keung, A J;Kiviet, D J;Kogenaru, M;Kostallas, G;Kwok, R;Laub, M T;Lee, S K;Lee, T I;Lee, T S;Li, G W;Lutz, R;Madar, D;Marguet, P;Mendoza, M C;Mitrophanov, A Y;Moon, T S;Morey, K J;Murphy, K F;Nandagopal, N;Nevozhay, D;Olson, E J;Rhodius, V A;Rodrigo, G;Rowland, M A;Rubens, J R;Rössger, K;Saito, H;Scialdone, A;Scott, M;Shen-Orr, S S;Shibata, T;Siryaporn, A;Skerker, J M;Slusarczyk, A L;Takahashi, M K;Takahashi, S;Tao, K;Vert, G;Weber, W;Wei, P;Wu, F Q;Zarrinpar, A
IV9PW
Cambridge, MA USA;Cambridge, MA USA.
26
null
5
null
31,492,904
Graham, Daniel;Jun, Tomi;Lu, Timothy K;Mueller, Isaak E;Rubens, Jacob R;Xavier, Ramnik
NAT COMMUN
Boston, MA USA;Cambridge, MA USA;New York, NY USA
Hamada, H;Hanai, T;Honjo, H;Iwasaki, K;Soma, Y;Tsuruno, K
10.1016/j.ymben.2019.08.007
null
525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
5v605b585f1z2i62rd4076h241de4iu3w47
Synthetic microbial consortium with specific roles designated by genetic circuits for cooperative chemical production
Kyushu Univ
null
Hanai, T (corresponding author), Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan.
null
Hamada, Hiroyuki;Hanai, Taizo;Honjo, Hiroshi;Iwasaki, Kenshiro;Soma, Yuki;Tsuruno, Keigo
Biotechnology & Applied Microbiology
JSPS KAKENHI [JP23119002, JP18K14065]; Chemical Innovation Encouragement Prize from Japan Association for Chemical Innovation; Sumitomo Foundation
WOS
Hanai, T
Kyushu Univ, Fukuoka, Japan
55
by;chemical;circuits;consortium;cooperative;designated;for;genetic;microbial;production;roles;specific;synthetic;with
1
Soma, Yuki
ACADEMIC PRESS INC ELSEVIER SCIENCE
Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan;Kyushu Univ, Med Inst Bioregulat, Res Ctr Trans Med, Div Metabol,Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan
Article
Kyushu Univ
SAN DIEGO
null
null
Kyushu Univ
Chemical Innovation Encouragement Prize from Japan Association for Chemical Innovation;JSPS KAKENHI;Sumitomo Foundation
Hanai, T (corresponding author), Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan.
275
Hamada, Hiroyuki;Hanai, Taizo;Honjo, Hiroshi;Iwasaki, Kenshiro;Soma, Yuki;Tsuruno, Keigo
63
2
482,582,100,028
Chemical Innovation Encouragement Prize from Japan Association for Chemical Innovation;JSPS KAKENHI [JP23119002, JP18K14065];Sumitomo Foundation
Japan
METABOLIC ENGINEERING
Japan
null
null
Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan
1096-7176
Hamada, H;Hanai, T;Honjo, H;Iwasaki, K;Soma, Y;Tsuruno, K
SEP
taizo@brs.kyushu-u.ac.jp
cooperative chemical production;genetic circuits;specific roles;synthetic microbial consortium
6
J
Biotechnology & Applied Microbiology
beta-glucosidase;biomass;capacities;CELLOBIOSE;chemical production;converts cellobiose;cooperative chemical production;desired cell density;developed;different synthetic genetic circuits;distributed tasks;divided synthetic metabolic pathway components;effective chemical production;efficient saccharification;enzyme;enzyme-producing strain;enzymes;Escherichia coli;ESCHERICHIA-COLI;expression;few consortia;FLUX;Genetic circuits;glucose;ISOPROPANOL PRODUCTION;LYSIS;lytic genes;metabolic pathway;microorganisms;release;results;sensor;single microorganisms;specific roles;synthetic genetic circuit;synthetic metabolic pathway;synthetic microbial consortia;synthetic microbial consortium;target chemical-producing strain;via
Honjo, H
CELLOBIOSE;ESCHERICHIA-COLI;EXPRESSION;FLUX;ISOPROPANOL PRODUCTION;LYSIS;metabolic pathway;SENSOR
268
[Honjo, Hiroshi; Iwasaki, Kenshiro; Soma, Yuki; Tsuruno, Keigo; Hamada, Hiroyuki; Hanai, Taizo] Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan. [Soma, Yuki] Kyushu Univ, Med Inst Bioregulat, Res Ctr Trans Med, Div Metabol,Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan.
This work was supported by JSPS KAKENHI Grant Numbers JP23119002, JP18K14065, Chemical Innovation Encouragement Prize from Japan Association for Chemical Innovation, and a Grant for a Basic Science Research Project from the Sumitomo Foundation.
beta-glucosidase;biomass;capacities;chemical production;converts cellobiose;desired cell density;developed;different synthetic genetic circuits;distributed tasks;divided synthetic metabolic pathway components;effective chemical production;efficient saccharification;enzyme;enzyme-producing strain;enzymes;Escherichia coli;few consortia;glucose;isopropanol production;lytic genes;microorganisms;release;results;single microorganisms;synthetic genetic circuit;synthetic metabolic pathway;synthetic microbial consortia;synthetic microbial consortium;target chemical-producing strain;via
10.1002/biot.201400422;10.1006/RWGN.2001.0106];10.1007/s00253-013-5504-7;10.1016/B978-0-12-385120-8.00002-4;10.1016/j.cell.2009.12.029;10.1016/j.ces.2013.03.021;10.1016/j.copbio.2008.07.009;10.1016/j.copbio.2014.12.022;10.1016/j.jbiosc.2012.02.019;10.1016/j.tibtech.2005.12.003;10.1016/j.tibtech.2008.05.004;10.1016/j.ymben.2012.08.006;10.1016/j.ymben.2014.02.008;10.1016/j.ymben.2015.04.005;10.1021/bp010018t;10.1021/sb400002n;10.1038/35002131;10.1038/msb.2008.24;10.1038/msb.2011.16;10.1038/msb4100187;10.1038/nature07389;10.1038/nature09565;10.1038/nature18930;10.1038/nbt.1937;10.1038/nbt.2149;10.1038/nbt.2899;10.1038/nbt.3095;10.1038/nbt.3796;10.1038/ncomms13858;10.1038/nrmicro3239;10.1038/s41589-018-0091-7;10.1073/pnas.0702609104;10.1073/pnas.93.18.9505;10.1128/AEM.01140-07;10.1128/AEM.01688-07;10.1186/1752-0509-8-S5-S7;10.1186/1754-1611-5-8;10.1371/journal.pone.0011909;[10.1038/NCHEMBIO.970, 10.1038/nchembio.970];[10.1038/NMETH.3727, 10.1038/nmeth.3727]
Kyushu Univ
Hamada, H;Hanai, T;Honjo, H;Iwasaki, K;Soma, Y;Tsuruno, K
Honjo, H: Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan
Soma, Yuki
JP18K14065;JP23119002
41
null
Japan
Kyushu Univ
Honjo, Hiroshi
null
CELLOBIOSE;ESCHERICHIA-COLI;EXPRESSION;FLUX;ISOPROPANOL PRODUCTION;LYSIS;METABOLIC PATHWAY;SENSOR
Honjo, Hiroshi; Iwasaki, Kenshiro; Soma, Yuki; Tsuruno, Keigo; Hamada, Hiroyuki; Hanai, Taizo;
null
Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan;Kyushu Univ, Med Inst Bioregulat, Res Ctr Trans Med, Div Metabol,Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan
Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan;Kyushu Univ, Med Inst Bioregulat, Res Ctr Trans Med, Div Metabol,Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan
1096-7184
null
null
1988;1996;2000;2001;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
36
Kyushu Univ, Grad Sch Syst Lifesci, Lab Bioinformat, Nishi Ku, 729 West Bldg 5,744 Motooka, Fukuoka, Fukuoka 8190395, Japan
Metab. Eng.
Hanai, Taizo
ACADEMIC PRESS INC ELSEVIER SCIENCE
,;a;an;and;are;been;benefits;beta-glucosidase;beyond;biomass;by;can;capacities;cell;cellobiose;chemical;chemical-producing;circuit;circuits;coli;components;composed;consisting;consortia;consortium;constructed;converts;demonstrate;density;designed;desired;destroys;developed;different;distributed;divided;effective;efficient;enzyme;enzyme-producing;enzymes;Escherichia;exert;express;few;for;from;functions;genes;genetic;glucose;grows;harbored;have;however;in;is;isopropanol;itself;lytic;metabolic;microbial;microorganisms;of;or;our;pathway;produce;production;programmed;reached;release;results;saccharification;single;strain;synthetic;target;tasks;that;the;to;until;using;via;was;we;when;which;with
Kyushu Univ
Synthetic microbial consortia consisting of microorganisms with different synthetic genetic circuits or divided synthetic metabolic pathway components can exert functions that are beyond the capacities of single microorganisms. However, few consortia of microorganisms with different synthetic genetic circuits have been developed. We designed and constructed a synthetic microbial consortium composed of an enzyme-producing strain and a target chemical-producing strain using Escherichia coli for chemical production with efficient saccharification. The enzyme-producing strain harbored a synthetic genetic circuit to produce beta-glucosidase, which converts cellobiose to glucose, destroys itself via the lytic genes, and release the enzyme when the desired cell density is reached. The target chemical-producing strain was programmed by a synthetic genetic circuit to express enzymes in the synthetic metabolic pathway for isopropanol production when the enzyme-producing strain grows until release of the enzyme. Our results demonstrate the benefits of synthetic microbial consortia with distributed tasks for effective chemical production from biomass.
ABI-7016-2020
CELLOBIOSE;ESCHERICHIA-COLI;EXPRESSION;FLUX;ISOPROPANOL PRODUCTION;LYSIS;METABOLIC PATHWAYS;SENSOR
9
null
null
8
ESCHERICHIA-COLI;CELLOBIOSE;EXPRESSION;FLUX;ISOPROPANOL PRODUCTION;LYSIS;METABOLIC PATHWAYS;SENSOR
WOS:000482582100028
Kyushu Univ, Fukuoka, Japan
Japan
2,019
null
0000-0003-1083-6824
null
null
English
null
ACS SYNTH BIOL;APPL ENVIRON MICROB;APPL MICROBIOL BIOT;BACTERIOPHAGES;BIOTECHNOL J;BIOTECHNOL PROGR;BMC SYST BIOL;CELL;CHEM ENG SCI;CURR OPIN BIOTECH;J Biol Eng;J BIOSCI BIOENG;METAB ENG;METHOD ENZYMOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT REV MICROBIOL;NATURE;P NATL ACAD SCI USA;PLOS ONE;TRENDS BIOTECHNOL
Hamada, Hiroyuki;Hanai, Taizo;Honjo, Hiroshi;Iwasaki, Kenshiro;Soma, Yuki;Tsuruno, Keigo
2024-03-11 ER
Balagadde, F K;Bonde, M T;Brenner, K;Brockman, I M;Brödel, A K;Calendar R.;Cameron, D E;Cox, R S;Desai, S H;Din, M O;Gardner, T S;Gupta, A;Hammer, K;Hanai, T;Haseltine, E L;Holtz, W J;Hsu, C Y;Kong, W T;Lee, J W;Levin-Karp, A;Lo, T M;Marguet, P;Morita, M;Nielsen, J;Park, J H;Pasotti, L;Prather, K L J;Salis, H M;Schaefer, A L;Smolke C. D.;Solomon, K V;Soma, Y;Stricker, J;Tamsir, A;Venayak, N;Vilanova, C;Xavier, J B;Zhang, F Z;Zhou, K
IT1BX
Fukuoka, Japan
43
null
1
null
31,401,244
Hamada, Hiroyuki;Hanai, Taizo;Honjo, Hiroshi;Iwasaki, Kenshiro;Soma, Yuki;Tsuruno, Keigo
METAB ENG
Fukuoka, Japan
Fan, K L;Li, H J;Li, K;Liu, H W;Wang, Q D;Xia, Y Z;Xun, L Y;Yang, Y Y
10.1021/acssynbio.9b00210
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
1i1l186v3l542b276a553v1c1d385t134x6q56g
Synthetic Gene Circuits Enable <i>Escherichia coli</i> To Use Endogenous H<sub>2</sub>S as a Signaling Molecule for Quorum Sensing
Shandong Univ
null
Xia, YZ; Xun, LY (corresponding author), Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China.;Xun, LY (corresponding author), Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA.
null
Fan, Kaili;Li, Huanjie;Li, Kai;Liu, Huaiwei;Wang, Qingda;Xia, Yongzhen;Xun, Luying;Yang, Yunyun
Biochemical Research Methods
National Key R&D Program of China [2018YFA0901200]; National Natural Science Foundation of China [31770093, 91751207]; Natural Science Foudation of Shandong Province [ZR2016CM03]
WOS
Xia, Y Z;Xun, L Y
Shandong Univ, Shandong, Peoples R China;Washington State Univ, Pullman, WA USA
8
<i>Escherichia;a;as;circuits;coli</i>;Enable;Endogenous;for;gene;H<sub>2</sub>S;Molecule;Quorum;Sensing;Signaling;synthetic;to;Use
2
Fan, Kaili;Li, Huanjie;Liu, Huaiwei;Xia, Yongzhen
AMER CHEMICAL SOC
LY (corresponding author), Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China.; Xun, LY (corresponding author), Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA;Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China;Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA
Article
Shandong Univ;Washington State Univ
WASHINGTON
null
null
Shandong Univ;Washington State Univ
National Key R&D Program of China;National Natural Science Foundation of China;Natural Science Foudation of Shandong Province
Xia, YZ; Xun, LY (corresponding author), Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China.; Xun, LY (corresponding author), Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA.
2120
Fan, Kaili;Li, Huanjie;Li, Kai;Liu, Huaiwei;Wang, Qingda;Xia, Yongzhen;Xun, Luying;Yang, Yunyun
69
2
487,577,300,017
National Key R&D Program of China [2018YFA0901200];National Natural Science Foundation of China [31770093, 91751207];Natural Science Foudation of Shandong Province [ZR2016CM03]
China;USA
ACS SYNTHETIC BIOLOGY
China;USA
null
null
Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China
2161-5063
Fan, K L;Li, H J;Li, K;Liu, H W;Wang, Q D;Xia, Y Z;Xun, L Y;Yang, Y Y
SEP
luying_xun@vetmed.wsu.edu;xiayongzhen2002@sdu.edu.cn
<i>Escherichia coli</i>;Endogenous H<sub>2</sub>S;Quorum Sensing;Signaling Molecule;synthetic gene circuits
8
J
Biochemistry & Molecular Biology
2);24 different circuits;<i>Escherichia coli</i>;ACIDS;adjustable sensitivity;autoinducer;autonomous switch;cell density;cell factories;CHEMISTRY;CIRCUITS;common metabolites;concentrations;designed synthetic gene;dynamic metabolic engineering;Endogenous H<sub>2</sub>S;Escherichia coli;Escherichia coli produced sulfide (H2S;gene expression;gene regulator CstR;growth phase;H2S-mediated gene circuits endowed E. coli cells;HS-;hydrogen sulfide;HYDROGEN-SULFIDE;indiffusible hydrogen polysulfide (HSnH;metabolic engineering;METABOLIC FLUX;microcolony;microorganisms;n;new tool-kit;OXIDOREDUCTASE;PATHWAY;production phase;quorum sensing;quorum sensing (QS);S2-);same batch;Signaling Molecule;sulfide/quinone oxidoreductase converted diffusible H2S;Sulfur;synchronous behaviors;synthetic biology;Synthetic gene circuit;synthetic gene circuits;THIOSULFATE;three element libraries;turn;use specific autoinducers;used H2S
Liu, H W
ACIDS;CHEMISTRY;dynamic metabolic engineering;Escherichia coli;hydrogen sulfide;HYDROGEN-SULFIDE;METABOLIC FLUX;OXIDOREDUCTASE;PATHWAY;quorum sensing;Sulfur;Synthetic gene circuit;THIOSULFATE
2113
[Liu, Huaiwei; Fan, Kaili; Li, Huanjie; Wang, Qingda; Yang, Yunyun; Li, Kai; Xia, Yongzhen; Xun, Luying] Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China. [Xun, Luying] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA.
The work was financially supported by grants of the National Key R&D Program of China (2018YFA0901200), the National Natural Science Foundation of China (31770093, 91751207), and the Natural Science Foudation of Shandong Province (ZR2016CM03).
2);24 different circuits;adjustable sensitivity;autoinducer;autonomous switch;cell density;cell factories;circuits;common metabolites;concentrations;designed synthetic gene;Escherichia coli produced sulfide (H2S;gene expression;gene regulator CstR;growth phase;H2S-mediated gene circuits endowed E. coli cells;HS-;indiffusible hydrogen polysulfide (HSnH;metabolic engineering;microcolony;microorganisms;n;new tool-kit;production phase;quorum sensing;quorum sensing (QS);S2-);same batch;sulfide/quinone oxidoreductase converted diffusible H2S;synchronous behaviors;synthetic biology;three element libraries;turn;use specific autoinducers;used H2S
10.1002/biot.201400422;10.1002/bit.20954;10.1002/prot.22665;10.1016/j.ab.2011.01.044;10.1016/j.biortech.2011.08.065;10.1016/j.copbio.2017.10.009;10.1016/j.copbio.2018.02.007;10.1016/j.freeradbiomed.2014.09.007;10.1016/j.redox.2017.02.021;10.1016/j.tim.2006.08.003;10.1016/j.ymben.2008.06.004;10.1016/j.ymben.2014.02.008;10.1016/j.ymben.2015.03.009;10.1021/ac60152a035;10.1021/ac60276a029;10.1021/sb300129j;10.1038/75398;10.1038/msb4100110;10.1038/nature24624;10.1038/nbt.3796;10.1038/nrmicro.2016.89;10.1038/s41564-017-0044-z;10.1038/s41589-018-0091-7;10.1038/srep14774;10.1073/pnas.1406401111;10.1073/pnas.1720770115;10.1093/nar/gky1169;10.1111/1462-2920.13511;10.1111/j.1751-908X.2009.00907.x;10.1111/mmi.13726;10.1126/science.1216379;10.1128/AEM.28.2.303-305.1974;10.1128/MMBR.69.1.12-50.2005;10.3390/molecules190812789
Shandong Univ
Fan, K L;Li, H J;Li, K;Liu, H W;Wang, Q D;Xia, Y Z;Xun, L Y;Yang, Y Y
Liu, H W: Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China
Li, Huanjie;Liu, Huaiwei
2018YFA0901200;31770093;91751207;ZR2016CM03
35
null
China
Shandong Univ;Washington State Univ
Liu, Huaiwei
null
ACIDS;CHEMISTRY;HYDROGEN-SULFIDE;METABOLIC FLUX;OXIDOREDUCTASE;PATHWAY;SULFUR;THIOSULFATE
Liu, Huaiwei; Fan, Kaili; Li, Huanjie; Wang, Qingda; Yang, Yunyun; Li, Kai; Xia, Yongzhen; Xun, Luying;
null
Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China;Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA
Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China;Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA
null
Escherichia coli;dynamic metabolic engineering;hydrogen sulfide;quorum sensing;Synthetic gene circuit
9
1959;1969;1974;2000;2005;2006;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
15
Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China;Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA
ACS Synth. Biol.
Xun, Luying
AMER CHEMICAL SOC
(H2S;(HSnH;(QS);,;2);24;=;>;a;adjustable;an;and;as;assembled;autoinducer;autoinducers;autonomous;batch;be;behaviors;biology;capable;cell;cells;circuits;coli;common;concentrations;constructed;converted;correlated;could;CstR;demonstrated;density;designed;different;diffusible;E.;element;endowed;engineering;Escherichia;expression;factories;for;from;gene;growth;H2S;H2S-mediated;herein;highly;HS-;hydrogen;indiffusible;its;latter;libraries;metabolic;metabolites;microcolony;microorganisms;n;new;of;often;on;or;other;oxidoreductase;phase;polysulfide;produced;production;proportionally;provide;quorum;regulator;S2-);same;sensed;sensing;sensitivity;specific;successfully;sulfide;sulfide/quinone;switch;synchronous;synthetic;than;that;the;them;then;these;three;thus;to;tool-kit;turn;use;used;using;we;which;with;within
Shandong Univ;Washington State Univ
Microorganisms often use specific autoinducers other than common metabolites for quorum sensing (QS). Herein, we demonstrated that Escherichia coli produced sulfide (H2S, HS-, and S2-) with the concentrations proportionally correlated to its cell density. We then designed synthetic gene circuits that used H2S as an autoinducer for quorum sensing. A sulfide/quinone oxidoreductase converted diffusible H2S to indiffusible hydrogen polysulfide (HSnH, n >= 2), and a gene regulator CstR sensed the latter to turn on the gene expression. We constructed three element libraries, with which 24 different circuits could be assembled for adjustable sensitivity to cell density. The H2S-mediated gene circuits endowed E. coli cells within the same batch or microcolony with highly synchronous behaviors. Using them we successfully constructed cell factories capable of an autonomous switch from growth phase to production phase. Thus, these circuits provide a new tool-kit for metabolic engineering and synthetic biology.
ABE-2328-2021;GOG-9430-2022
ACID;CHEMISTRY;HYDROGEN-SULFIDE;METABOLIC FLUX;OXIDOREDUCTASE;PATHWAY;SULFUR;THIOSULFATE
3
null
dynamic metabolic engineering;Escherichia coli;hydrogen sulfide;quorum sensing;Synthetic gene circuit
15
ESCHERICHIA-COLI;ACID;CHEMISTRY;dynamic metabolic engineering;hydrogen sulfide;METABOLIC FLUX;OXIDOREDUCTASE;PATHWAY;quorum sensing;Sulfur;synthetic gene circuits;THIOSULFATE
WOS:000487577300017
Shandong Univ, Shandong, Peoples R China;Washington State Univ, Pullman, WA USA
China;USA
2,019
null
0000-0001-9950-1910;0000-0002-0483-5318;0000-0002-4611-771X;0000-0002-4997-0927
null
null
English
null
ACS SYNTH BIOL;ANAL BIOCHEM;ANAL CHEM;APPL MICROBIOL;BIORESOUR BIOPROCESS;BIORESOURCE TECHNOL;BIOTECHNOL BIOENG;BIOTECHNOL J;CURR OPIN BIOTECH;ENVIRON MICROBIOL;FREE RADICAL BIO MED;GEOSTAND GEOANAL RES;METAB ENG;MICROBIOL MOL BIOL R;MOL MICROBIOL;MOL SYST BIOL;MOLECULES;NAT BIOTECHNOL;NAT CHEM BIOL;NAT MICROBIOL;NAT REV MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PROTEINS;REDOX BIOL;SCI REP-UK;SCIENCE;TRENDS MICROBIOL
Fan, Kaili;Li, Huanjie;Li, Kai;Liu, Huaiwei;Wang, Qingda;Xia, Yongzhen;Xun, Luying;Yang, Yunyun
2024-03-11 ER
Anesiadis, N;Bareia, T;Brockman, I M;Farmer, W R;Giedroc, D P;Gupta, A;Kamyshny, A;Karig, D;Kelly, D P;Kimura, Y;Kong, W;Kong, W T;Lalwani, M A;Lara, A R;Lien, O G;Liu, H;Liu, H W;Lloyd, D;Longo, D;Maker, M D;Marcia, M;Munsky, B;Olson, K R;Ono, K;Papenfort, K;Soma, Y;Toohey, J I;Whiteley, M;Wolfe, A J;Xia, Y Z;Xin, Y F;Xu, P
JA1LA
Pullman, WA USA;Shandong, Peoples R China.
18
null
2
null
31,386,360
Fan, Kaili;Li, Huanjie;Li, Kai;Liu, Huaiwei;Wang, Qingda;Xia, Yongzhen;Xun, Luying;Yang, Yunyun
ACS SYNTH BIOL
Pullman, WA USA;Shandong, Peoples R China
Isilak, M E;Kehribar, E S;Lu, T K;Olmez, T T;Seker, U O S
10.1021/acssynbio.9b00235
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
6z695s392z1r4f6r181d2y1c5v29v2e5n2j5in
Synthetic Genetic Circuits for Self-Actuated Cellular Nanomaterial Fabrication Devices
Bilkent Univ
null
Seker, UOS (corresponding author), Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey.
null
Isilak, Musa Efe;Kehribar, Ebru Sahin;Lu, Timothy K;Olmez, Tolga Tarkan;Seker, Urartu Ozgur Safak
Biochemical Research Methods
TUBITAK [114M163, 115Z217]; TUBAGEBIP Award
WOS
Seker, U O S
Bilkent Univ, Ankara, Turkey;MIT, Cambridge, MA USA
8
Cellular;circuits;devices;Fabrication;for;genetic;Nanomaterial;Self-Actuated;synthetic
2
Seker, Urartu;Ölmez, Tolga Tarkan
AMER CHEMICAL SOC
Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey;MIT, Dept Biol Engn, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA
Article
Bilkent Univ
WASHINGTON
null
null
Bilkent Univ;MIT
TUBAGEBIP Award;TUBITAK
Seker, UOS (corresponding author), Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey.
2162
Isilak, Musa Efe;Kehribar, Ebru Sahin;Lu, Timothy K;Olmez, Tolga Tarkan;Seker, Urartu Ozgur Safak
39
2
487,577,300,021
TUBAGEBIP Award;TUBITAK [114M163, 115Z217]
Turkey;USA
ACS SYNTHETIC BIOLOGY
Turkey
null
null
Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey
2161-5063
Isilak, M E;Kehribar, E S;Lu, T K;Olmez, T T;Seker, U O S
SEP
urartu@bilkent.edu.tr
Self-Actuated Cellular Nanomaterial Fabrication Devices;synthetic genetic circuits
5
J
Biochemistry & Molecular Biology
autonomous living material;BACTERIAL SENSORS;biofilms;biomaterials;BIOMINERALIZATION;biosilica;biosystems;cadmium;cells;CIRCUITS;controlled synthetic biosystems;corresponding extracellular matrix;CURLI BIOGENESIS;detection;ESCHERICHIA-COLI;Genetic circuits;gold;green approach;hard tissues;IN-VITRO;iron ions;living cells;materials;materials synthesis module;METALLOTHIONEINS;NANOCRYSTALS;nanomagnets;nanomaterial precursor-sensing module (sensor);nanomaterial synthesis;nanomaterials;nanoscale materials;natural ability;ORGANISMS;PEPTIDE-SYNTHESIS;potential;precursor ion;proof-of-concept study;PROTEIN;proteins;PSEUDOMONAS-AERUGINOSA;related nanomaterial-nucleating extracellular matrix;Self-Actuated Cellular Nanomaterial Fabrication Devices;sensor;solid materials;synthesis;synthetic biology;synthetic genetic circuits;SYSTEM;variety;whole-cell biosensors;wide range
Olmez, T T
BACTERIAL SENSORS;biofilms;BIOMINERALIZATION;CURLI BIOGENESIS;ESCHERICHIA-COLI;Genetic circuits;IN-VITRO;METALLOTHIONEINS;NANOCRYSTALS;nanomaterials;PEPTIDE-SYNTHESIS;PROTEIN;PSEUDOMONAS-AERUGINOSA;Synthetic biology;whole-cell biosensors
2152
[Olmez, Tolga Tarkan; Kehribar, Ebru Sahin; Isilak, Musa Efe; Seker, Urartu Ozgur Safak] Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey. [Lu, Timothy K.] MIT, Dept Biol Engn, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
This study was supported by TUBITAK (Grant Nos. 114M163 and 115Z217). U.O.S.S. acknowledges the TUBAGEBIP Award.
autonomous living material;biomaterials;biosilica;biosystems;cadmium;cells;circuits;controlled synthetic biosystems;corresponding extracellular matrix;detection;gold;green approach;hard tissues;iron ions;living cells;materials;materials synthesis module;nanomagnets;nanomaterial precursor-sensing module (sensor);nanomaterial synthesis;nanomaterials;nanoscale materials;natural ability;organisms;potential;precursor ion;proof-of-concept study;proteins;related nanomaterial-nucleating extracellular matrix;sensor;solid materials;synthesis;synthetic genetic circuits;system;variety;wide range
10.1002/anie.200903572;10.1002/bit.260191010;10.1006/jmbi.2000.3682;10.1007/BF02738153;10.1007/s00253-006-0718-6;10.1007/s11051-012-1218-5;10.1016/j.bbamcr.2013.09.010;10.1016/j.biomaterials.2007.05.040;10.1016/j.bpj.2016.12.036;10.1016/j.copbio.2016.11.023;10.1016/j.jcis.2018.03.016;10.1016/j.str.2011.05.015;10.1016/S0006-291X(03)01366-4;10.1016/S0168-6445(03)00051-2;10.1021/acssensors.7b00728;10.1021/acssynbio.6b00166;10.1021/ar300321e;10.1021/cr8002328;10.1021/cr990115p;10.1021/es702688c;10.1021/ja907454f;10.1021/ja909406n;10.1021/jz2016473;10.1021/la047428m;10.1021/la104942t;10.1021/la500160p;10.1021/nn202566n;10.1021/nn900720g;10.1038/35015043;10.1038/35101627;10.1038/ncomms5945;10.1038/ncomms9747;10.1038/nmat758;10.1038/nmat964;10.1038/nrmicro3253;10.1038/s41598-017-01442-8;10.1038/s41598-017-13613-8;10.1039/c2sc01119k;10.1039/c7ra06289c;10.1073/pnas.0703310104;10.1073/pnas.0832310100;10.1073/pnas.2433456100;10.1073/pnas.90.14.6385;10.1074/jbc.270.45.26723;10.1093/nar/gkm631;10.1099/00221287-144-5-1407;10.1104/pp.123.3.825;10.1111/mmi.12515;10.1126/science.1082387;10.1128/AEM.02343-17;10.1128/JB.00122-16;10.1128/JB.180.9.2280-2284.1998;10.1128/JB.180.9.2442-2449.1998;10.1128/JB.185.23.6826-6840.2003;10.1146/annurev.arplant.53.100301.135154;10.1146/annurev.micro.60.080805.142106;10.2976/1.2896331;10.3762/bjoc.10.118;[10.1038/NCHEM.1025, 10.1038/nchem.1025];[10.1038/NMETH.1318, 10.1038/nmeth.1318]
Bilkent Univ
Isilak, M E;Kehribar, E S;Lu, T K;Olmez, T T;Seker, U O S
Olmez, T T: Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey
Lu, Timothy K;Seker, Urartu;Ölmez, Tolga Tarkan;Ölmez, Tolga Tarkan T
114M163;115Z217
61
null
Turkey
Bilkent Univ;MIT
Olmez, Tolga Tarkan
null
BACTERIAL SENSORS;BIOMINERALIZATION;CURLI BIOGENESIS;ESCHERICHIA-COLI;IN-VITRO;METALLOTHIONEINS;NANOCRYSTALS;PEPTIDE-SYNTHESIS;PROTEIN;PSEUDOMONAS-AERUGINOSA
Olmez, Tolga Tarkan; Kehribar, Ebru Sahin; Isilak, Musa Efe; Lu, Timothy K.; Seker, Urartu Ozgur Safak;
null
Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey;MIT, Dept Biol Engn, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA
Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey;MIT, Dept Biol Engn, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA
null
biofilm;Genetic circuits;nanomaterials;Synthetic biology;whole-cell biosensor
9
1977;1993;1995;1998;1999;2000;2001;2002;2003;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
10
Bilkent Univ, UNAM Inst Mat & Nanotechnol, Ankara, Turkey
ACS Synth. Biol.
Seker, Urartu Ozgur Safak
AMER CHEMICAL SOC
(sensor);,;:;a;ability;an;and;approach;are;as;autonomous;availability;be;being;biomaterials;biosilica;biosystems;cadmium;cells;circuits;consisting;controlled;corresponding;coupled;create;dedicated;demonstrate;designed;detection;detects;developed;enables;encode;endowing;engineered;express;extended;extracellular;form;genetic;genetically;gold;green;hard;has;have;ion;ions;iron;living;many;material;materials;matrix;modeled;module;nanomagnets;nanomaterial;nanomaterial-nucleating;nanomaterials;nanoscale;natural;of;on;or;organisms;potential;precursor;precursor-sensing;presence;proof-of-concept;proteins;range;related;sense;sensor;shows;solid;study;such;synthesis;synthesize;synthesizing;synthetic;system;that;the;these;they;this;tissues;to;triggers;using;variety;we;when;wide;with
Bilkent Univ
Genetically controlled synthetic biosystems are being developed to create nanoscale materials. These biosystems are modeled on the natural ability of living cells to synthesize materials: many organisms have dedicated proteins that synthesize a wide range of hard tissues and solid materials, such as nanomagnets and biosilica. We designed an autonomous living material synthesizing system consisting of engineered cells with genetic circuits that synthesize nanomaterials. The circuits encode a nanomaterial precursor-sensing module (sensor) coupled with a materials synthesis module. The sensor detects the presence of cadmium, gold, or iron ions, and this detection triggers the synthesis of the related nanomaterial-nucleating extracellular matrix. We demonstrate that when engineered cells sense the availability of a precursor ion, they express the corresponding extracellular matrix to form the nanomaterials. This proof-of-concept study shows that endowing cells with synthetic genetic circuits enables nanomaterial synthesis and has the potential to be extended to the synthesis of a variety of nanomaterials and biomaterials using a green approach.
AAF-7261-2020;C-8309-2012;F-4299-2010;G-4267-2012
BACTERIAL SENSORS;BIOMINERALIZATION;CURLI BIOGENESIS;ESCHERICHIA-COLI;IN-VITRO;METALLOTHIONEIN;NANOCRYSTALS;PEPTIDE-SYNTHESIS;PROTEIN;PSEUDOMONAS-AERUGINOSA
3
null
biofilms;Genetic circuits;nanomaterials;Synthetic biology;whole-cell biosensors
21
ESCHERICHIA-COLI;PSEUDOMONAS-AERUGINOSA;BACTERIAL SENSORS;biofilms;BIOMINERALIZATION;CURLI BIOGENESIS;Genetic circuits;IN-VITRO;Metallothionein;NANOCRYSTALS;nanomaterials;PEPTIDE-SYNTHESIS;PROTEIN;Synthetic biology;WHOLE-CELL BIOSENSOR
WOS:000487577300021
Bilkent Univ, Ankara, Turkey;MIT, Cambridge, MA USA
Turkey;USA
2,019
null
0000-0002-5272-1876;0000-0002-8818-4507
null
null
English
null
ACCOUNTS CHEM RES;ACS NANO;ACS SENSORS;ACS SYNTH BIOL;ANGEW CHEM INT EDIT;ANNU REV MICROBIOL;ANNU REV PLANT BIOL;APPL ENVIRON MICROB;APPL MICROBIOL BIOT;BBA-MOL CELL RES;BEILSTEIN J ORG CHEM;BIOCHEM BIOPH RES CO;BIOMATERIALS;BIOPHYS J;BIOTECHNOL BIOENG;CELL BIOCHEM BIOPHYS;CHEM REV;CHEM SCI;CURR OPIN BIOTECH;ENVIRON SCI TECHNOL;FEMS MICROBIOL REV;HFSP J;J AM CHEM SOC;J BACTERIOL;J BIOL CHEM;J COLLOID INTERF SCI;J MOL BIOL;J NANOPART RES;J PHYS CHEM LETT;LANGMUIR;MICROBIOL-UK;MOL MICROBIOL;NAT CHEM;NAT COMMUN;NAT MATER;NAT METHODS;NAT REV MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLANT PHYSIOL;RSC ADV;SCI REP-UK;SCIENCE;STRUCTURE;WHOLE CELL SENSING S
Isilak, Musa Efe;Kehribar, Ebru Sahin;Lu, Timothy K;Olmez, Tolga Tarkan;Seker, Urartu Ozgur Safak
2024-03-11 ER
Banerjee, I A;Barbas, C F;Barnhart, M M;Briggs, B D;Brocklehurst, K R;Brown, N L;Brown, S;Chen, C L;Chen, Z;Chiu, C Y;Cobbett, C;Cobbett, C S;Cui, Y Y;Daunert, S;Dickerson, M B;Evans, M L;Gibson, D G;Golec, P;Hammer, N D;Jungmann, R;Kalyoncu, E;Karube, I;Kunkle, C A;Kwon, S;Lamour, G;Lee, J Y;Lower, B H;Mao, C B;Mäde, V;Naik, R R;Neilands, J B;Nguyen, P Q;Nikel, P I;Onur, T;Rauser, W E;Reches, M;Roehrich, A;Roggo, C;Sakaguchi, T;Saltepe, B;Sano, K I;Sarikaya, M;Seker, U O S;Shimomura-Shimizu M.;Sousa, C;Taglialegna, A;Tamerler, C;Tan, Y N;Taylor, J D;Tesson, B;Van Gerven, N;Vidal, O;Wang, L Y;Wei, W;Whaley, S R;White, C;Whiteley, M;Yagi, K;Zhou, W
JA1LA
Ankara, Turkey
12
null
2
null
31,419,103
Isilak, Musa Efe;Kehribar, Ebru Sahin;Lu, Timothy K;Olmez, Tolga Tarkan;Seker, Urartu Ozgur Safak
ACS SYNTH BIOL
Ankara, Turkey;Cambridge, MA USA
Chang, T H;Chiang, V L;Hsu, T S;Hung, E T;Jiang, J;Kao, C T;Kuan, C Y;Li, W;Lin, C C;Lin, Y C J;Liu, G F;Ma, H Y;Miao, F;Qu, G Z;Tsai, N C;Wang, J P;Wang, Z F;Yeh, C S;Yu, J H;Zhou, C G
10.1101/gr.245951.118
null
1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
4e6t4t3d1z712m5u6o5w6n505bka2dp13x3
A novel synthetic-genetic-array-based yeast one-hybrid system for high discovery rate and short processing time
Acad Sinica
null
Chang, TH (corresponding author), Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan.;Chiang, VL; Lin, YCJ (corresponding author), North Carolina State Univ, Dept Forestry & Environm Resources, Forest Biotechnol Grp, Raleigh, NC 27695 USA.;Li, W; Chiang, VL; Lin, YCJ (corresponding author), Northeast Forestry Univ, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China.;Lin, YCJ (corresponding author), Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei 10617, Taiwan.;Lin, YCJ (corresponding author), Natl Taiwan Univ, Coll Life Sci, Inst Plant Biol, Taipei 10617, Taiwan.
null
Chang, Tien-Hsien;Chiang, Vincent L;Hsu, Tzu-Shu;Hung, Er-Tsi;Jiang, Jing;Kao, Chung-Ting;Kuan, Chen-Yu;Li, Wei;Lin, Chia-Chang;Lin, Ying-Chung Jimmy;Liu, Guifeng;Ma, Hongyan;Miao, Fang;Qu, Guan-Zheng;Tsai, Ni-Chiao;Wang, Jack P;Wang, Zhifeng;Yeh, Chung-Shu;Yu, Jhong-He;Zhou, Chenguang
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology;Genetics & Heredity
National Natural Science Foundation of China (NSFC) [31522014]; China 1000-Talents Plan for young researchers; Taiwan Ministry of Science and Technology [MOST 105-2311-B-001-059]; Academia Sinica (Taiwan); MOST [106-0210-01-15-02, 107-0210-01-19-01]; Academia Sinica Thematic Project [AS-103-TP-B12]; Taiwan MOST [106-2311-B-002-001-MY2, 107-2636-B-002-003]; MOST Young Scholar Fellowship Columbus Program; Academia Sinica Postdoctoral Fellowship; NSFC [31430093]; U.S. National Science Foundation [DBI-0922391]; U.S. Office of Science (Biological and Environmental Research), Department of Energy [DE-SC000691]; North Carolina State University Jordan Family Distinguished Professor Endowment; North Carolina State University Forest Biotechnology Industrial Research Consortium
WOS
Chang, T H;Chiang, V L;Li, W;Lin, Y C J
Acad Sinica, Taipei, Taiwan;Natl Taiwan Univ, Taipei, Taiwan;Natl Yang Ming Univ, Taipei, Taiwan;North Carolina State Univ, Raleigh, NC USA;Northeast Forestry Univ, Harbin, Peoples R China
29
a;and;discovery;for;high;novel;one-hybrid;processing;rate;short;synthetic-genetic-array-based;system;time;yeast
3
KAO, CHUNG-TING;Kuan, chen-yu;Li, Wei;Wang, Jack P.
COLD SPRING HARBOR LAB PRESS
Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan;Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan.; Li, W; Chiang, VL; Lin, YCJ (corresponding author), Northeast Forestry Univ, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China.; Lin, YCJ (corresponding author), Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei 10617, Taiwan.; Lin, YCJ (corresponding author), Natl Taiwan Univ, Coll Life Sci, Inst Plant Biol, Taipei 10617, Taiwan.; Chiang, VL; Lin, YCJ (corresponding author), North Carolina State Univ, Dept Forestry & Environm Resources, Forest Biotechnol Grp, Raleigh, NC 27695 USA;Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei 10617, Taiwan;Natl Taiwan Univ, Coll Life Sci, Inst Plant Biol, Taipei 10617, Taiwan;Natl Yang Ming Univ, Ctr Syst & Synthet Biol, Taipei 11221, Taiwan;Natl Yang Ming Univ, Inst Biomed Informat, Taipei 11221, Taiwan;North Carolina State Univ, Dept Forestry & Environm Resources, Forest Biotechnol Grp, Raleigh, NC 27695 USA;Northeast Forestry Univ, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China
Article
Acad Sinica;North Carolina State Univ;Natl Taiwan Univ;Northeast Forestry Univ
COLD SPRING HARBOR
null
null
Acad Sinica;Natl Taiwan Univ;Natl Yang Ming Univ;North Carolina State Univ;Northeast Forestry Univ
Academia Sinica (Taiwan);Academia Sinica Postdoctoral Fellowship;Academia Sinica Thematic Project;China 1000-Talents Plan for young researchers;MOST;MOST Young Scholar Fellowship Columbus Program;National Natural Science Foundation of China (NSFC);North Carolina State University Forest Biotechnology Industrial Research Consortium;North Carolina State University Jordan Family Distinguished Professor Endowment;NSFC;Taiwan Ministry of Science and Technology;Taiwan MOST;U.S. National Science Foundation;U.S. Office of Science (Biological and Environmental Research), Department of Energy
Chang, TH (corresponding author), Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan.; Li, W; Chiang, VL; Lin, YCJ (corresponding author), Northeast Forestry Univ, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China.; Lin, YCJ (corresponding author), Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei 10617, Taiwan.; Lin, YCJ (corresponding author), Natl Taiwan Univ, Coll Life Sci, Inst Plant Biol, Taipei 10617, Taiwan.; Chiang, VL; Lin, YCJ (corresponding author), North Carolina State Univ, Dept Forestry & Environm Resources, Forest Biotechnol Grp, Raleigh, NC 27695 USA.
1351
Chang, Tien-Hsien;Chiang, Vincent L;Hsu, Tzu-Shu;Hung, Er-Tsi;Jiang, Jing;Kao, Chung-Ting;Kuan, Chen-Yu;Li, Wei;Lin, Chia-Chang;Lin, Ying-Chung Jimmy;Liu, Guifeng;Ma, Hongyan;Miao, Fang;Qu, Guan-Zheng;Tsai, Ni-Chiao;Wang, Jack P;Wang, Zhifeng;Yeh, Chung-Shu;Yu, Jhong-He;Zhou, Chenguang
41
7
482,830,700,012
Academia Sinica (Taiwan);Academia Sinica Postdoctoral Fellowship;Academia Sinica Thematic Project [AS-103-TP-B12];China 1000-Talents Plan for young researchers;MOST [106-0210-01-15-02, 107-0210-01-19-01];MOST Young Scholar Fellowship Columbus Program;National Natural Science Foundation of China (NSFC) [31522014];North Carolina State University Forest Biotechnology Industrial Research Consortium;North Carolina State University Jordan Family Distinguished Professor Endowment;NSFC [31430093];Taiwan Ministry of Science and Technology [MOST 105-2311-B-001-059];Taiwan MOST [106-2311-B-002-001-MY2, 107-2636-B-002-003];U.S. National Science Foundation [DBI-0922391];U.S. Office of Science (Biological and Environmental Research), Department of Energy [DE-SC000691]
China;Taiwan;USA
GENOME RESEARCH
China;Taiwan.;;USA
null
null
Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan
1088-9051
Chang, T H;Chiang, V L;Hsu, T S;Hung, E T;Jiang, J;Kao, C T;Kuan, C Y;Li, W;Lin, C C;Lin, Y C J;Liu, G F;Ma, H Y;Miao, F;Qu, G Z;Tsai, N C;Wang, J P;Wang, Z F;Yeh, C S;Yu, J H;Zhou, C G
AUG
chang108@gate.sinica.edu.tw;vchiang@ncsu.edu;weili2015@nefu.edu.cn;ycjimmylin@ntu.edu.tw
high discovery rate;novel synthetic-genetic-array-based yeast one-hybrid system;short processing time
20
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology;Genetics & Heredity
ASSAYS;chromatin immunoprecipitation;comprehensive genome-scale gene regulatory networks;conventional diploid-mating approach;deletion;DNA cis targets;DNA INTERACTIONS;eukaryotic gene expression;FAMILIES;haploid-transformation method;high;high discovery rate;high-throughput;high-throughput meiosis-directed yeast one-hybrid system;highest accuracy;identifying TF-DNA interactions;interactions;LIGNIN;Magic Markers;meiosis-directed YIH system;novel;novel synthetic-genetic-array-based yeast one-hybrid system;one;one-tenth;ORGANISMS;processing time;PROTEIN;REGULATORY NETWORK;short processing time;SND1 TRANSCRIPTION FACTOR;synthetic genetic array analysis;SYSTEM;transcription factor-DNA interaction discovery rate;transcription factors (TFs);unique features;used methods;vivo;WOOD FORMATION;yeast one-hybrid (YIH)
Yeh, C S
ASSAYS;DELETION;DNA INTERACTIONS;FAMILIES;HIGH-THROUGHPUT;LIGNIN;PROTEIN;REGULATORY NETWORK;SND1 TRANSCRIPTION FACTOR;WOOD FORMATION
1343
[Yeh, Chung-Shu; Chang, Tien-Hsien] Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan. [Wang, Zhifeng; Ma, Hongyan; Zhou, Chenguang; Qu, Guan-Zheng; Jiang, Jing; Liu, Guifeng; Wang, Jack P.; Li, Wei; Chiang, Vincent L.; Lin, Ying-Chung Jimmy] Northeast Forestry Univ, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China. [Miao, Fang; Kao, Chung-Ting; Hsu, Tzu-Shu; Yu, Jhong-He; Hung, Er-Tsi; Lin, Chia-Chang; Kuan, Chen-Yu; Tsai, Ni-Chiao; Lin, Ying-Chung Jimmy] Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei 10617, Taiwan. [Miao, Fang; Kao, Chung-Ting; Hsu, Tzu-Shu; Yu, Jhong-He; Hung, Er-Tsi; Lin, Chia-Chang; Kuan, Chen-Yu; Tsai, Ni-Chiao; Lin, Ying-Chung Jimmy] Natl Taiwan Univ, Coll Life Sci, Inst Plant Biol, Taipei 10617, Taiwan. [Hsu, Tzu-Shu] Natl Yang Ming Univ, Inst Biomed Informat, Taipei 11221, Taiwan. [Hsu, Tzu-Shu] Natl Yang Ming Univ, Ctr Syst & Synthet Biol, Taipei 11221, Taiwan. [Wang, Jack P.; Chiang, Vincent L.; Lin, Ying-Chung Jimmy] North Carolina State Univ, Dept Forestry & Environm Resources, Forest Biotechnol Grp, Raleigh, NC 27695 USA.
W.L. is supported by the National Natural Science Foundation of China (NSFC 31522014) and China 1000-Talents Plan for young researchers. T.-H.C. is supported by the Taiwan Ministry of Science and Technology (MOST 105-2311-B-001-059), Academia Sinica (Taiwan) and MOST (106-0210-01-15-02 and 107-0210-01-19-01), and Academia Sinica Thematic Project (AS-103-TP-B12). Y.-C.J.L. is supported by Taiwan MOST (106-2311-B-002-001-MY2 and 107-2636-B-002-003) and MOST Young Scholar Fellowship Columbus Program. C.-S.Y. is supported by an Academia Sinica Postdoctoral Fellowship. V.L.C. is supported by the NSFC Grant (31430093), U.S. National Science Foundation, Plant Genome Research Program Grant DBI-0922391, U.S. Office of Science (Biological and Environmental Research), Department of Energy Grant DE-SC000691, North Carolina State University Jordan Family Distinguished Professor Endowment, and North Carolina State University Forest Biotechnology Industrial Research Consortium.
chromatin immunoprecipitation;comprehensive genome-scale gene regulatory networks;conventional diploid-mating approach;DNA cis targets;eukaryotic gene expression;haploid-transformation method;high;high-throughput meiosis-directed yeast one-hybrid system;highest accuracy;identifying TF-DNA interactions;interactions;Magic Markers;meiosis-directed YIH system;novel;one;one-tenth;organisms;processing time;synthetic genetic array analysis;system;transcription factor-DNA interaction discovery rate;transcription factors (TFs);unique features;used methods;vivo;yeast one-hybrid (YIH)
10.1007/s00425-016-2640-1;10.1016/j.cell.2006.04.038;10.1016/j.cell.2015.03.003;10.1016/j.cell.2016.04.038;10.1016/j.molp.2016.10.020;10.1016/j.ymeth.2012.07.027;10.1016/S0092-8674(88)90469-2;10.1016/S0580-9517(06)36016-3;10.1038/nature14099;10.1038/NMETH.1240;10.1038/NMETH1063;10.1038/nprot.2014.146;10.1038/nprot.2014.147;10.1038/s41586-018-0656-3;10.1073/pnas.1212977109;10.1073/pnas.1714422114;10.1091/mbc.E15-08-0573;10.1093/nar/gkx608;10.1093/treephys/tpx093;10.1093/treephys/tpx121;10.1101/pdb.prot4590;10.1104/pp.106.086678;10.1105/tpc.113.117697;10.1105/tpc.113.120881;10.1111/j.1469-8137.2012.04201.x;10.1111/nph.15505;10.1111/tpj.12162;10.1126/science.1065810;10.1126/science.1182213;10.1126/science.8266075;10.1177/1087057103256465;10.1177/1087057114534298;[10.1038/NMETH.1748, 10.1038/nmeth.1748];[10.1038/NMETH.1750, 10.1038/nmeth.1750];[10.1038/NMETH.1763, 10.1038/nmeth.1763]
Acad Sinica
Chang, T H;Chiang, V L;Hsu, T S;Hung, E T;Jiang, J;Kao, C T;Kuan, C Y;Li, W;Lin, C C;Lin, Y C J;Liu, G F;Ma, H Y;Miao, F;Qu, G Z;Tsai, N C;Wang, J P;Wang, Z F;Yeh, C S;Yu, J H;Zhou, C G
Yeh, C S: Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan
wang, jack;Zhou, Chenguang
106-0210-01-15-02;106-2311-B-002-001-MY2;107-0210-01-19-01;107-2636-B-002-003;31430093;31522014;AS-103-TP-B12;DBI-0922391;DE-SC000691;MOST 105-2311-B-001-059
37
null
Taiwan
Acad Sinica;Natl Taiwan Univ;Natl Yang Ming Univ;North Carolina State Univ;Northeast Forestry Univ
Yeh, Chung-Shu
Green Published, hybrid, Green Submitted
ASSAYS;DELETION;DNA INTERACTIONS;FAMILIES;HIGH-THROUGHPUT;LIGNIN;PROTEIN;REGULATORY NETWORK;SND1 TRANSCRIPTION FACTOR;WOOD FORMATION
Yeh, Chung-Shu; Wang, Zhifeng; Miao, Fang; Ma, Hongyan; Kao, Chung-Ting; Hsu, Tzu-Shu; Yu, Jhong-He; Hung, Er-Tsi; Lin, Chia-Chang; Kuan, Chen-Yu; Tsai, Ni-Chiao; Zhou, Chenguang; Qu, Guan-Zheng; Jiang, Jing; Liu, Guifeng; Wang, Jack P.; Li, Wei; Chiang, Vincent L.; Chang, Tien-Hsien; Lin, Ying-Chung Jimmy;
null
Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan;Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei 10617, Taiwan;Natl Taiwan Univ, Coll Life Sci, Inst Plant Biol, Taipei 10617, Taiwan;Natl Yang Ming Univ, Ctr Syst & Synthet Biol, Taipei 11221, Taiwan;Natl Yang Ming Univ, Inst Biomed Informat, Taipei 11221, Taiwan;North Carolina State Univ, Dept Forestry & Environm Resources, Forest Biotechnol Grp, Raleigh, NC 27695 USA;Northeast Forestry Univ, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China
Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan;Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei 10617, Taiwan;Natl Taiwan Univ, Coll Life Sci, Inst Plant Biol, Taipei 10617, Taiwan;Natl Yang Ming Univ, Ctr Syst & Synthet Biol, Taipei 11221, Taiwan;Natl Yang Ming Univ, Inst Biomed Informat, Taipei 11221, Taiwan;North Carolina State Univ, Dept Forestry & Environm Resources, Forest Biotechnol Grp, Raleigh, NC 27695 USA;Northeast Forestry Univ, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China
1549-5469
null
8
1988;1993;1998;2001;2003;2006;2007;2008;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
17
Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan;Natl Taiwan Univ, Coll Life Sci, Dept Life Sci, Taipei 10617, Taiwan;Natl Taiwan Univ, Coll Life Sci, Inst Plant Biol, Taipei 10617, Taiwan;North Carolina State Univ, Dept Forestry & Environm Resources, Forest Biotechnol Grp, Raleigh, NC 27695 USA;Northeast Forestry Univ, State Key Lab Tree Genet & Breeding, Harbin 150040, Peoples R China
Genome Res.
Lin, Ying-Chung Jimmy
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
(TFs);(YIH);,;a;accuracy;also;analysis;and;approach;array;as;authenticated;be;between;by;can;chromatin;cis;comprehensive;constructing;conventional;developed;diploid-mating;discover;discovery;DNA;eukaryotic;expression;extensively;factor-DNA;factors;features;for;gene;genetic;genome-scale;haploid-transformation;has;high;high-throughput;highest;identifying;immunoprecipitation;in;interaction;interactions;is;Magic;Markers;meiosis-directed;method;methods;most;nearly;networks;novel;of;offers;often;one;one-hybrid;one-tenth;organisms;particularly;processing;rate;regulated;regulatory;suited;synthetic;system;targets;TF-DNA;that;the;their;these;this;tightly;time;to;transcription;twice;unique;used;using;various;vivo;we;with;yeast;YIH
Acad Sinica;Natl Taiwan Univ;North Carolina State Univ;Northeast Forestry Univ
Eukaryotic gene expression is often tightly regulated by interactions between transcription factors (TFs) and their DNA cis targets. Yeast one-hybrid (YIH) is one of the most extensively used methods to discover these interactions. We developed a high-throughput meiosis-directed yeast one-hybrid system using the Magic Markers of the synthetic genetic array analysis. The system has a transcription factor-DNA interaction discovery rate twice as high as the conventional diploid-mating approach and a processing time nearly one-tenth of the haploid-transformation method. The system also offers the highest accuracy in identifying TF-DNA interactions that can be authenticated in vivo by chromatin immunoprecipitation. With these unique features, this meiosis-directed YIH system is particularly suited for constructing novel and comprehensive genome-scale gene regulatory networks for various organisms.
E-7931-2010;JLL-8637-2023
ASSAY;DELETION;DNA INTERACTION;FAMILY;HIGH-THROUGHPUT;LIGNIN;PROTEIN;REGULATORY NETWORKS;SND1 TRANSCRIPTION FACTOR;WOOD FORMATION
4
null
null
9
ASSAY;DELETION;DNA INTERACTION;FAMILY;HIGH-THROUGHPUT;LIGNIN;PROTEIN;REGULATORY NETWORKS;SND1 TRANSCRIPTION FACTOR;WOOD FORMATION
WOS:000482830700012
Acad Sinica, Taipei, Taiwan;Natl Taiwan Univ, Taipei, Taiwan;Natl Yang Ming Univ, Taipei, Taiwan;North Carolina State Univ, Raleigh, NC USA;Northeast Forestry Univ, Harbin, Peoples R China
China;Taiwan;USA
2,019
null
0000-0002-1176-4802;0000-0002-4407-9334;0000-0002-5392-0076;0000-0002-8232-963X
null
null
English
null
CELL;CSH Protoc;J BIOMOL SCREEN;METHOD MICROBIOL;METHODS;METHODS MOL BIOL;MOL BIOL CELL;MOL PLANT;NAT METHODS;NAT PROTOC;NATURE;NEW PHYTOL;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLANT CELL;PLANT J;PLANT PHYSIOL;PLANTA;SCIENCE;TREE PHYSIOL;YEAST
Chang, Tien-Hsien;Chiang, Vincent L;Hsu, Tzu-Shu;Hung, Er-Tsi;Jiang, Jing;Kao, Chung-Ting;Kuan, Chen-Yu;Li, Wei;Lin, Chia-Chang;Lin, Ying-Chung Jimmy;Liu, Guifeng;Ma, Hongyan;Miao, Fang;Qu, Guan-Zheng;Tsai, Ni-Chiao;Wang, Jack P;Wang, Zhifeng;Yeh, Chung-Shu;Yu, Jhong-He;Zhou, Chenguang
2024-03-11 ER
Bass, J I F;Brachmann, C B;Chan, Y F;Deplancke Bart;Deplancke, B;French, S;Gaudinier, A;Hens, K;Iglesias-Fernández, R;Li, J J;Li, Q Z;Li, W;Lin, Y C;Lin, Y C J;Lundholt, B K;Mangat, C S;O'Malley, R C;Petzold, H E;Reece-Hoyes, J S;Romano, J M;Shi, R;Solomon, M J;Suzuki, S;Taylor-Teeples, M;Tong Amy Hin Yan;Tong, A H Y;Typas, A;Vermeirssen, V;Wang, J P;Xu, C Z;Yan, X J;Yang, F;Yeh, C S
IT4KV
Harbin, Peoples R China.;Raleigh, NC USA;Taipei, Taiwan.
17
null
5
null
31,186,303
Chang, Tien-Hsien;Chiang, Vincent L;Hsu, Tzu-Shu;Hung, Er-Tsi;Jiang, Jing;Kao, Chung-Ting;Kuan, Chen-Yu;Li, Wei;Lin, Chia-Chang;Lin, Ying-Chung Jimmy;Liu, Guifeng;Ma, Hongyan;Miao, Fang;Qu, Guan-Zheng;Tsai, Ni-Chiao;Wang, Jack P;Wang, Zhifeng;Yeh, Chung-Shu;Yu, Jhong-He;Zhou, Chenguang
GENOME RES
Harbin, Peoples R China;Raleigh, NC USA;Taipei, Taiwan
Arbulu, S;Cintas, L M;Feito, J;Gútiez, L;Hernández, P E;Herranz, C;Jiménez, J J
10.1016/j.foodres.2019.01.015
null
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
4y3p4i1axp644tp4l116f2h3b5806lk1t
Cloning and expression of synthetic genes encoding native, hybrid- and bacteriocin-derived chimeras from mature class IIa bacteriocins, by <i>Pichia pastoris</i> (syn. <i>Komagataella</i> spp.)
UCM
null
Hernández, PE (corresponding author), UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain.
null
Arbulu, Sara;Cintas, Luis M;Feito, Javier;Gutiez, Loreto;Hernandez, Pablo E;Herranz, Carmen;Jimenez, Juan J
Food Science & Technology
Ministerio de Economia y Competitividad (MINECO) [AGL2012-34829]; Comunidad de Madrid (CAM) [S2013/ABI-2747]; Universidad Complutense of Madrid (UCM), Spain [FEI 16/54]; MINECO; Ministerio de Ciencia e Innovacion (MICINN); Ministerio de Education y Ciencia (MEC), Spain
WOS
Hernández, P E
ACD Pharmaceut AS, Leknes, Norway;CESAG Univ Pontificia Comillas, Palma De Mallorca, Spain;TEAGASC, Cork, Ireland;UCM, Madrid, Spain;Univ Coll Cork, Cork, Ireland
121
(syn;,;<i>Pichia;and;bacteriocin-derived;bacteriocins;by;chimeras;class;cloning;encoding;expression;From;genes;hybrid-;i>Komagataella</i>;IIa;mature;native;of;pastoris</i>;spp;synthetic
3
Arbulu, Sara;Cintas, Luis M.;Feito, Javier;Hernandez, Pablo E.
ELSEVIER
ACD Pharmaceut AS, Leknes, Norway;CESAG Univ Pontificia Comillas, Palma De Mallorca, Spain;TEAGASC, Food Res Ctr, Fermoy, Cork, Ireland;UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain;Univ Coll Cork, APC Microbiome Ireland, Cork, Ireland
Article
UCM
AMSTERDAM
null
null
ACD Pharmaceut AS;CESAG Univ Pontificia Comillas;Secc Dept Nutr & Ciencia Alimentos;TEAGASC;UCM;Univ Coll Cork
Comunidad de Madrid (CAM);MINECO;Ministerio de Ciencia e Innovacion (MICINN);Ministerio de Economia y Competitividad (MINECO);Ministerio de Education y Ciencia (MEC), Spain;Universidad Complutense of Madrid (UCM), Spain
Hernández, PE (corresponding author), UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain.
899
Arbulu, Sara;Cintas, Luis M;Feito, Javier;Gutiez, Loreto;Hernandez, Pablo E;Herranz, Carmen;Jimenez, Juan J
43
5
470,048,200,096
Comunidad de Madrid (CAM) [S2013/ABI-2747];MINECO;Ministerio de Ciencia e Innovacion (MICINN);Ministerio de Economia y Competitividad (MINECO) [AGL2012-34829];Ministerio de Education y Ciencia (MEC), Spain;Universidad Complutense of Madrid (UCM), Spain [FEI 16/54]
Ireland;Norway;Spain
FOOD RESEARCH INTERNATIONAL
Spain
null
null
UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain
0963-9969
Arbulu, S;Cintas, L M;Feito, J;Gútiez, L;Hernández, P E;Herranz, C;Jiménez, J J
JUL
cherranz@vet.ucm.es;ehernan@vet.ucm.es;j.feito@ucm.es;jjjm@vet.ucm.es;lcintas@vet.ucm.es;lgutiez@vet.ucm.es;sara.arbulu@pdi.ucm.es
<i>Pichia pastoris</i> (syn;bacteriocin-derived chimeras;expression;hybrid-;i>Komagataella</i> spp;mature class IIa bacteriocins;synthetic genes encoding native
7
J
Food Science & Technology
(a);(b);(c);(EntA);<i>Pichia pastoris</i> (syn;antimicrobial activity;ANTIMICROBIAL PEPTIDE;bacteriocin-derived chimeras;bacteriocins produced;biologically-produced bacteriocin-derived chimera;C-terminal end;class IIa bacteriocins enterocin HF (EntHF);different Listeria strains;direct antimicrobial activity;EntA;EntCRL35;enterocin;enterocin CRL35 (EntCRL35);enterocin P (EntP);ENTEROCOCCUS-FAECIUM T136;EntHF;EntHF chimera;EntHF peptide;EntP;expected molecular mass;expression;FUNCTIONAL EXPRESSION;fusion;Heterologous bacteriocin production;higher specific antimicrobial activity;highest antimicrobial activity;hSUMO3-fused bacteriocins;hybrid bacteriocins;hybrid-;Hybrid- and bacteriocin-derived chimeras;i>Komagataella</i> spp;IMMUNITY;L. monocytogenes;LACTIC-ACID BACTERIA;MALDI-TOF MS analysis;mature class IIa bacteriocins;MRM-ESI-LC-MS/MS (QTRAP) analysis;multi-step chromatographic purified fractions;N-terminal region;native amino acid sequence;Native bacteriocins;optimization;P. pastoris;P. pastoris producers;P. pastoris X-33;P13;peptides;permitted detection;Pichia pastoris;plasmid pP-alpha hSUMO3;plasmid pPICZ alpha;processing;producer;production;purified fractions;recognition;recombinant P. pastoris;SAMPLES;SEC-DEPENDENT BACTERIOCIN;secretion;supernatants;synthetic counterpart;synthetic EntP;synthetic genes;synthetic genes encoding EntHF;synthetic genes encoding native;tri-glycine peptide linker
Arbulu, S
ANTIMICROBIAL PEPTIDE;ENTEROCOCCUS-FAECIUM T136;FUNCTIONAL EXPRESSION;Heterologous bacteriocin production;Hybrid- and bacteriocin-derived chimeras;IMMUNITY;LACTIC-ACID BACTERIA;MALDI-TOF MS analysis;MRM-ESI-LC-MS/MS (QTRAP) analysis;Native bacteriocins;OPTIMIZATION;P13;Pichia pastoris;RECOGNITION;SEC-DEPENDENT BACTERIOCIN;Synthetic genes
888
[Arbulu, Sara; Jimenez, Juan J.; Gutiez, Loreto; Feito, Javier; Cintas, Luis M.; Herranz, Carmen; Hernandez, Pablo E.] UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain. [Arbulu, Sara] Univ Coll Cork, APC Microbiome Ireland, Cork, Ireland. [Arbulu, Sara] TEAGASC, Food Res Ctr, Fermoy, Cork, Ireland. [Jimenez, Juan J.] ACD Pharmaceut AS, Leknes, Norway. [Gutiez, Loreto] CESAG Univ Pontificia Comillas, Palma De Mallorca, Spain.
Financial support was provided by project AGL2012-34829 from the Ministerio de Economia y Competitividad (MINECO), by grant S2013/ABI-2747 from the Comunidad de Madrid (CAM) and by Fund FEI 16/54 from the Universidad Complutense of Madrid (UCM), Spain. S. Arbulu held a fellowship (FPI) from the MINECO. J.J. Jimenez held a fellowship (FPI) from the Ministerio de Ciencia e Innovacion (MICINN) and L. Gutiez held a fellowship (FPU) from the Ministerio de Education y Ciencia (MEC), Spain.
(a);(b);(c);(EntA);antimicrobial activity;bacteriocin-derived chimeras;bacteriocins produced;biologically-produced bacteriocin-derived chimera;C-terminal end;class IIa bacteriocins enterocin HF (EntHF);different Listeria strains;direct antimicrobial activity;EntA;EntCRL35;enterocin;enterocin CRL35 (EntCRL35);enterocin P (EntP);EntHF;EntHF chimera;EntHF peptide;EntP;expected molecular mass;expression;fusion;higher specific antimicrobial activity;highest antimicrobial activity;hSUMO3-fused bacteriocins;hybrid bacteriocins;hybrid-;L. monocytogenes;MRM-ESI-LC-MS/MS (QTRAP) analysis;multi-step chromatographic purified fractions;N-terminal region;native amino acid sequence;P. pastoris;P. pastoris producers;P. pastoris X-33;peptides;permitted detection;plasmid pP-alpha hSUMO3;plasmid pPICZ alpha;processing;producer;production;purified fractions;recombinant P. pastoris;samples;secretion;supernatants;synthetic counterpart;synthetic EntP;synthetic genes;synthetic genes encoding EntHF;tri-glycine peptide linker
10.1002/pmic.200900398;10.1002/yea.1542;10.1007/978-1-4419-7692-5_8;10.1007/s00253-012-4257-z;10.1007/s00253-015-6470-z;10.1007/s00253-016-7343-9;10.1007/s10295-013-1302-6;10.1007/s11947-010-0465-7;10.1007/s12033-014-9731-7;10.1016/j.copbio.2007.07.005;10.1016/j.copbio.2017.07.011;10.1016/j.fob.2012.01.002;10.1016/j.jbiotec.2011.07.038;10.1016/j.jbiotec.2016.04.024;10.1016/j.pep.2015.09.022;10.1021/acs.biochem.5b01306;10.1021/acs.jafc.5b03882;10.1021/bi991351x;10.1021/ja3089229;10.1038/nmeth.3213;10.1038/nrmicro1273;10.1038/nrmicro2937;10.1038/s41598-017-09102-7;10.1073/pnas.0608775104;10.1074/jbc.M204928200;10.1074/jbc.M412712200;10.1093/bioinformatics/btq054;10.1099/00221287-143-7-2287;10.1099/mic.0.052571-0;10.1111/j.1365-2958.2008.06279.x;10.1111/lam.12246;10.1128/AAC.48.7.2778-2781.2004;10.1128/AAC.49.7.3004-3008.2005;10.1128/AEM.00530-12;10.1128/AEM.01173-10;10.1128/AEM.02528-17;10.1128/AEM.02559-07;10.1128/AEM.03477-14;10.1128/AEM.63.11.4321-4330.1997;10.1128/JB.00777-10;10.1155/2015/767183;10.1186/1471-2164-9-S2-S27;10.1186/s12866-016-0840-2;10.1371/journal.pone.0037915;10.1371/journal.pone.0075347;10.1371/journal.pone.0103456;10.2174/138920109787048661;10.3109/09687688.2011.602219
UCM
Arbulu, S;Cintas, L M;Feito, J;Gútiez, L;Hernández, P E;Herranz, C;Jiménez, J J
Arbulu, S: UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain
Arbulu, Sara;Cintas, Luis M;Feito, Javier;Hernandez, Pablo E.;Herranz, Carmen
AGL2012-34829;FEI 16/54;S2013/ABI-2747
50
null
Spain
ACD Pharmaceut AS;CESAG Univ Pontificia Comillas;TEAGASC;UCM;Univ Coll Cork
Arbulu, Sara
null
ANTIMICROBIAL PEPTIDE;ENTEROCOCCUS-FAECIUM T136;FUNCTIONAL EXPRESSION;IMMUNITY;LACTIC-ACID BACTERIA;OPTIMIZATION;P13;RECOGNITION;SEC-DEPENDENT BACTERIOCIN
Arbulu, Sara; Jimenez, Juan J.; Gutiez, Loreto; Feito, Javier; Cintas, Luis M.; Herranz, Carmen; Hernandez, Pablo E.;
null
ACD Pharmaceut AS, Leknes, Norway;CESAG Univ Pontificia Comillas, Palma De Mallorca, Spain;TEAGASC, Food Res Ctr, Fermoy, Cork, Ireland;UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain;Univ Coll Cork, APC Microbiome Ireland, Cork, Ireland
ACD Pharmaceut AS, Leknes, Norway;CESAG Univ Pontificia Comillas, Palma De Mallorca, Spain;TEAGASC, Food Res Ctr, Fermoy, Cork, Ireland;UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain;Univ Coll Cork, APC Microbiome Ireland, Cork, Ireland
1873-7145
Heterologous bacteriocin production;Hybrid- and bacteriocin-derived chimeras;MALDI-TOF MS analysis;MRM-ESI-LC-MS/MS (QTRAP) analysis;Native bacteriocins;Pichia pastoris;Synthetic gene
null
1997;1999;2002;2004;2005;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
14
UCM, Secc Dept Nutr & Ciencia Alimentos, Nutr Bromatol Higene & Seguridad Alimentaria, Fac Vet, Ave Puerta Hierro S-N, Madrid 28040, Spain
Food Res. Int.
Hernandez, Pablo E
ELSEVIER
(a);(b);(c);(EntA);(EntCRL35);(EntHF);(EntP);(QTRAP);,;:;a;acid;activity;against;alpha;also;amino;analysis;and;antimicrobial;bacteriocin-derived;bacteriocins;biologically-produced;by;C-terminal;chimera;chimeras;chromatographic;class;cloned;compared;counterpart;CRL35;derived;designed;detection;devised;different;direct;displayed;drive;encoding;end;EntA;EntCRL35;enterocin;EntHF;EntP;expected;expressing;expression;for;fractions;from;fusion;genes;HF;higher;highest;hSUMO3;hSUMO3-fused;hybrid;hybrid-;IIa;important;in;including;its;itself;L.;linker;Listeria;mass;molecular;monocytogenes;more;MRM-ESI-LC-MS/MS;multi-step;N-terminal;native;of;only;P;P.;pastoris;peptide;peptides;permitted;plasmid;pP-alpha;pPICZ;processing;produced;producer;producers;production;purified;recombinant;region;samples;secretion;seems;sequence;showed;shows;specific;strains;suggest;supernatants;synthetic;than;that;the;their;this;through;to;tri-glycine;were;whereas;with;work;X-33
UCM
In this work, synthetic genes designed from (a), the native amino acid sequence of the class IIa bacteriocins enterocin HF (EntHF) and enterocin CRL35 (EntCRL35), (b) from hybrid bacteriocins derived from fusion of enterocin A (EntA) to itself and to EntHF and EntCRL35 through a tri-glycine peptide linker, and (c) from bacteriocin-derived chimeras devised from fusion of the N-terminal region of EntA and enterocin P (EntP) to the C-terminal end of EntHF and EntCRL35, were cloned in plasmid pPICZ alpha A for expression by P. pastoris X-33. Synthetic genes encoding EntHF and EntCRL35 were also cloned in plasmid pP-alpha hSUMO3 for expression of the hSUMO3-fused bacteriocins by P. pastoris. Only recombinant P. pastoris expressing the bacteriocin-derived chimeras displayed a direct antimicrobial activity whereas P. pastoris X-33, producer of EntP::EntHF, showed the highest antimicrobial activity in their supernatants and in the multi-step chromatographic purified fractions. The MRM-ESI-LC-MS/MS (QTRAP) analysis of purified fractions from P. pastoris producers of hybrid- and bacteriocin-derived chimeras, permitted detection in the samples of peptides with the expected molecular mass of the bacteriocins produced. The antimicrobial activity of the EntP::EntHF chimera compared to that of the synthetic EntP::EntHF peptide, suggest that the biologically-produced bacteriocin-derived chimera shows a higher specific antimicrobial activity than its synthetic counterpart against different Listeria strains, including L. monocytogenes. More important, the N-terminal region of EntA and EntP seems to drive the production, processing and secretion of hybrid- and bacteriocin-derived chimeras, by P. pastoris X-33.
AAN-7273-2020;C-7030-2017;H-1694-2017;P-8701-2014;Z-6308-2019
ANTIMICROBIAL PEPTIDES;ENTEROCOCCUS-FAECIUM T136;FUNCTIONAL EXPRESSION;IMMUNIZATION;LACTIC-ACID BACTERIA;OPTIMIZATION;P13;RECOGNITION;SEC-DEPENDENT BACTERIOCIN
4
null
Heterologous bacteriocin production;Hybrid- and bacteriocin-derived chimeras;MALDI-TOF MS analysis;MRM-ESI-LC-MS/MS (QTRAP) analysis;Native bacteriocins;Pichia pastoris;Synthetic genes
12
Antimicrobial peptides;ENTEROCOCCUS-FAECIUM T136;FUNCTIONAL EXPRESSION;Heterologous bacteriocin production;Hybrid- and bacteriocin-derived chimeras;IMMUNIZATION;LACTIC-ACID BACTERIA;MALDI-TOF MS analysis;MRM-ESI-LC-MS/MS (QTRAP) analysis;Native bacteriocins;OPTIMIZATION;P13;Pichia pastoris;RECOGNITION;SEC-DEPENDENT BACTERIOCIN;Synthetic gene
WOS:000470048200096
ACD Pharmaceut AS, Leknes, Norway;CESAG Univ Pontificia Comillas, Palma De Mallorca, Spain;TEAGASC, Cork, Ireland;UCM, Madrid, Spain;Univ Coll Cork, Cork, Ireland
Ireland;Norway;Spain
2,019
null
0000-0001-6259-8456;0000-0001-9889-3692;0000-0003-1774-3372;0000-0003-4161-0385
null
null
English
null
ANTIMICROB AGENTS CH;APPL ENVIRON MICROB;APPL MICROBIOL BIOT;BIOCHEMISTRY-US;BIOINFORMATICS;BIOMED RES INT;BMC GENOMICS;BMC MICROBIOL;CURR OPIN BIOTECH;CURR OPIN FOOD SCI;CURR PHARM BIOTECHNO;FEBS OPEN BIO;FOOD BIOPROCESS TECH;J AGR FOOD CHEM;J AM CHEM SOC;J BACTERIOL;J BIOL CHEM;J BIOTECHNOL;J IND MICROBIOL BIOT;LETT APPL MICROBIOL;MICROBIOL-SGM;MOL BIOTECHNOL;MOL MICROBIOL;NAT METHODS;NAT REV MICROBIOL;P NATL ACAD SCI USA;PLOS ONE;PROTEIN EXPRES PURIF;PROTEOMICS;PYMOL MOL GRAPH SYST;SCI REP-UK;YEAST
Arbulu, Sara;Cintas, Luis M;Feito, Javier;Gutiez, Loreto;Hernandez, Pablo E;Herranz, Carmen;Jimenez, Juan J
2024-03-11 ER
Acedo, J Z;Acuña, L;Alvarez-Sieiro, P;Arbulu, S;Borrero, J;Casaus, P;Chikindas, M L;Cintas, L M;Cotter, P D;De La Cruz, S;Delano W. L.;Diep, D B;Field, D;Geng M.;Gutiérrez, J;Jiménez, J J;Johnsen, L;Kjos, M;Lohans, C T;Love, K R;Maclean, B;Malmström, J;Ni, Z H;Nissen-Meyer, J;O'Connor, P M;Papo, N;Puxbaum, V;Saavedra, L;Sanchez, J;Tileva, M;Tiwari, S K;Tymoszewska, A;Wang, X J;Wang, Y J;Yang, J Y;Yang, S;Zhang, C;Zhang, M J;Zhang, Y;Zhao, Y M
IB1TQ
Madrid, Spain
15
null
5
null
31,108,822
Arbulu, Sara;Cintas, Luis M;Feito, Javier;Gutiez, Loreto;Hernandez, Pablo E;Herranz, Carmen;Jimenez, Juan J
FOOD RES INT
Cork, Ireland;Leknes, Norway;Madrid, Spain;Palma De Mallorca, Spain
He, X L;Liang, F Y;Lin, R S;Shi, C Y;Wang, B;Xiao, Y L;Yao, Y Q;Zhang, M S;Zhou, B
10.1094/PHYTO-07-18-0266-R
null
3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA
74986od301u5l10f666z6e3o2z5u1q1a1q21
Systematic Identification of Pathogenic <i>Streptomyces</i> sp. AMCC400023 That Causes Common Scab and Genomic Analysis of Its Pathogenicity Island
Shandong Agr Univ
null
Zhou, B (corresponding author), Natl Engn Lab Efficient Utilizat Soil & Fertilize, Tai An 271018, Shandong, Peoples R China.;Zhou, B; Wang, B (corresponding author), Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China.
null
He, Xiaoli;Liang, Feiyang;Lin, Rongshan;Shi, Chunyu;Wang, Bing;Xiao, Yunli;Yao, Yaqian;Zhang, Mingshuo;Zhou, Bo
Plant Sciences
National Key RD Program [2017YFD0201100, 2017YFD0800200]; Shandong Province Potato Industry Innovation Team Chief Expert Project [SDAIT-16-01]
WOS
Wang, B;Zhou, B
Natl Engn Lab Efficient Utilizat Soil & Fertilize, Shandong, Peoples R China;Shandong Agr Univ, Shandong, Peoples R China;Shandong Plant Protect Stn, Shandong, Peoples R China
109
<i>Streptomyces</i>;AMCC400023;Analysis;and;Causes;Common;Genomic;Identification;Island;its;of;Pathogenic;Pathogenicity;Scab;sp;systematic;that
1
Liang, Feiyang;Zhou, Bo
AMER PHYTOPATHOLOGICAL SOC
B (corresponding author), Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China.; Zhou, B (corresponding author), Natl Engn Lab Efficient Utilizat Soil & Fertilize, Tai An 271018, Shandong, Peoples R China;Natl Engn Lab Efficient Utilizat Soil & Fertilize, Tai An 271018, Shandong, Peoples R China;Shandong Agr Univ, Agr Coll, Tai An 271018, Shandong, Peoples R China;Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China;Shandong Plant Protect Stn, Linyi, Shandong, Peoples R China
Article
Natl Engn Lab Efficient Utilizat Soil & Fertilize;Shandong Agr Univ
ST PAUL
null
null
Natl Engn Lab Efficient Utilizat Soil & Fertilize;Shandong Agr Univ;Shandong Plant Protect Stn
National Key RD Program;Shandong Province Potato Industry Innovation Team Chief Expert Project
Zhou, B; Wang, B (corresponding author), Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China.; Zhou, B (corresponding author), Natl Engn Lab Efficient Utilizat Soil & Fertilize, Tai An 271018, Shandong, Peoples R China.
1128
He, Xiaoli;Liang, Feiyang;Lin, Rongshan;Shi, Chunyu;Wang, Bing;Xiao, Yunli;Yao, Yaqian;Zhang, Mingshuo;Zhou, Bo
39
4
473,667,800,003
National Key RD Program [2017YFD0201100, 2017YFD0800200];Shandong Province Potato Industry Innovation Team Chief Expert Project [SDAIT-16-01]
China
PHYTOPATHOLOGY
China
null
null
Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China
0031-949X
He, X L;Liang, F Y;Lin, R S;Shi, C Y;Wang, B;Xiao, Y L;Yao, Y Q;Zhang, M S;Zhou, B
JUL
bwang@sdau.edu.cn;zhoubo2798@163.com
AMCC400023;Common Scab;Genomic Analysis;Pathogenic <i>Streptomyces</i> sp;Pathogenicity Island;systematic Identification
9
J
Plant Sciences
16S ribosomal RNA analyses;31 Streptomyces genomes;31 Streptomyces species;accurate taxonomic status;AMCC400023;analyses;ANI;average nucleotide identity (ANI);biochemical characteristics;China;close homologous relationship;close relationship;collinearity analysis;colonization region;Common Scab;complete pathogenicity island (PAI) composition;data;detection;distinct phytopathogen;DNA-DNA HYBRIDIZATION;formed;genome level;Genomic Analysis;Hebei Province;horizontal gene transfer;isDDH analyses;least;member;PAI;PAI structure mapping;pathogen strain;Pathogenic <i>Streptomyces</i> sp;pathogenicity;Pathogenicity Island;PHYLOGENETIC ANALYSIS;phylogenetic relationships;phylogenetic tree;phytotoxin thaxtomin A.;PHYTOTOXINS;PLANT PATHOGENICITY;POTATO;potato common scab;potato scab;potato scabs;potato tuber slice assay;potato-growing areas;potted back experiment;radish seedling test;results;RIBOSOMAL-RNA GENE;S. scabiei;S. scabiei 87-22;same time;sequence;serious soilborne disease;severe economic losses;silico DNADNA hybridization (isDDH);SP-NOV;species level;Streptomyces scabiei;Streptomyces sp;Streptomyces spp.;Streptomyces strain AMCC400023;synthetic gene cluster tree construction;systematic Identification;taxonomic status;test strain Streptomyces sp;thaxtomin;THAXTOMIN BIOSYNTHESIS;toxicity-related genes;toxin region;two pathogens;VIRULENCE;whole genome;whole-genome level
Liang, F Y
DNA-DNA HYBRIDIZATION;PHYLOGENETIC ANALYSIS;PHYTOTOXINS;PLANT PATHOGENICITY;POTATO;RIBOSOMAL-RNA GENE;SEQUENCE;SP-NOV;THAXTOMIN BIOSYNTHESIS;VIRULENCE
1115
[Liang, Feiyang; Lin, Rongshan; Yao, Yaqian; Zhang, Mingshuo; He, Xiaoli; Zhou, Bo; Wang, Bing] Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China. [Xiao, Yunli] Shandong Plant Protect Stn, Linyi, Shandong, Peoples R China. [Shi, Chunyu] Shandong Agr Univ, Agr Coll, Tai An 271018, Shandong, Peoples R China. [Zhou, Bo] Natl Engn Lab Efficient Utilizat Soil & Fertilize, Tai An 271018, Shandong, Peoples R China.
This work was partially supported by National Key R&D Program grants 2017YFD0201100 and 2017YFD0800200 and funding from Shandong Province Potato Industry Innovation Team Chief Expert Project grant SDAIT-16-01.
16S ribosomal RNA analyses;31 Streptomyces genomes;31 Streptomyces species;accurate taxonomic status;AMCC400023;analyses;ANI;average nucleotide identity (ANI);biochemical characteristics;China;close homologous relationship;close relationship;collinearity analysis;colonization region;complete pathogenicity island (PAI) composition;data;detection;distinct phytopathogen;formed;genome level;Hebei Province;horizontal gene transfer;isDDH analyses;least;member;PAI;PAI structure mapping;pathogen strain;pathogenicity;phylogenetic relationships;phylogenetic tree;phytotoxin thaxtomin A.;potato common scab;potato scab;potato scabs;potato tuber slice assay;potato-growing areas;potted back experiment;radish seedling test;results;S. scabiei;S. scabiei 87-22;same time;serious soilborne disease;severe economic losses;silico DNADNA hybridization (isDDH);species level;Streptomyces scabiei;Streptomyces sp;Streptomyces spp.;Streptomyces strain AMCC400023;synthetic gene cluster tree construction;taxonomic status;test strain Streptomyces sp;thaxtomin;toxicity-related genes;toxin region;two pathogens;whole genome;whole-genome level
10.1007/s00203-007-0225-x;10.1007/s10482-008-9240-4;10.1007/s10482-010-9429-1;10.1007/s10482-011-9656-0;10.1007/s10482-015-0556-6;10.1007/s10482-015-0610-4;10.1007/s12230-017-9575-3;10.1016/j.plasmid.2010.11.002;10.1016/j.pmpp.2007.09.003;10.1016/j.syapm.2016.04.001;10.1016/S0065-2911(00)42003-5;10.1021/jf00044a042;10.1038/417141a;10.1038/ja.2005.1;10.1039/c39890000849;10.1046/j.1365-2958.2000.02170.x;10.1073/pnas.0906412106;10.1074/jbc.M112.420182;10.1093/bioinformatics/btu033;10.1093/femspd/ftw107;10.1093/nar/17.19.7843;10.1093/nar/30.11.2478;10.1093/nar/gkh340;10.1093/nar/gkr1293;10.1094/MPMI-04-16-0068-R;10.1094/MPMI-09-16-0190-R;10.1094/MPMI-20-6-0599;10.1094/MPMI-20-7-0751;10.1094/MPMI-23-2-0161;10.1094/MPMI-23-9-1164;10.1094/PDIS-93-12-1329;10.1094/PDIS.1997.81.8.836;10.1094/Phyto-80-606;10.1094/Phyto-85-537;10.1094/Phyto-86-709;10.1094/PHYTO-96-1363;10.1094/PHYTO.1999.89.6.462;10.1099/00207713-39-4-387;10.1099/00207713-39-4-393;10.1099/00207713-46-3-635;10.1099/00207713-48-2-495;10.1099/00207713-50-1-91;10.1099/ijs.0.02624-0;10.1099/ijs.0.02629-0;10.1099/ijs.0.64483-0;10.1099/ijs.0.65224-0;10.1101/gr.1224503;10.1111/j.1365-2958.2004.04461.x;10.1111/j.1365-2958.2007.05942.x;10.1111/j.1365-3059.2012.02619.x;10.1111/j.1365-3059.2012.02659.x;10.1111/j.1574-6968.2006.00368.x;10.1111/j.1574-6976.2007.00072.x;10.1111/jam.12369;10.1111/mpp.12296;10.1128/AEM.68.2.738-744.2002;10.1128/JB.01010-08;10.1128/JB.186.5.1362-1373.2004;10.1128/MMBR.63.2.266-292.1999;10.1146/annurev.phyto.44.032905.091147;10.1186/1471-2105-14-60;10.1186/1471-2105-5-113;10.1186/1471-2164-9-75;10.1371/journal.pone.0099345;10.1371/journal.ppat.1006811;10.4056/sigs.531120;[10.1111/J.1364-3703.2009.00561.X, 10.1111/j.1364-3703.2009.00561.x]
Shandong Agr Univ
He, X L;Liang, F Y;Lin, R S;Shi, C Y;Wang, B;Xiao, Y L;Yao, Y Q;Zhang, M S;Zhou, B
Liang, F Y: Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China
li, zhang;Zhang, Lijun;Zhou, Bo
2017YFD0201100;2017YFD0800200;SDAIT-16-01
73
null
China
Natl Engn Lab Efficient Utilizat Soil & Fertilize;Shandong Agr Univ;Shandong Plant Protect Stn
Liang, Feiyang
hybrid
DNA-DNA HYBRIDIZATION;PHYLOGENETIC ANALYSIS;PHYTOTOXINS;PLANT PATHOGENICITY;POTATO;RIBOSOMAL-RNA GENE;SEQUENCE;SP-NOV;THAXTOMIN BIOSYNTHESIS;VIRULENCE
Liang, Feiyang; Lin, Rongshan; Yao, Yaqian; Xiao, Yunli; Zhang, Mingshuo; Shi, Chunyu; He, Xiaoli; Zhou, Bo; Wang, Bing;
null
Natl Engn Lab Efficient Utilizat Soil & Fertilize, Tai An 271018, Shandong, Peoples R China;Shandong Agr Univ, Agr Coll, Tai An 271018, Shandong, Peoples R China;Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China;Shandong Plant Protect Stn, Linyi, Shandong, Peoples R China
Natl Engn Lab Efficient Utilizat Soil & Fertilize, Tai An 271018, Shandong, Peoples R China;Shandong Agr Univ, Agr Coll, Tai An 271018, Shandong, Peoples R China;Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China;Shandong Plant Protect Stn, Linyi, Shandong, Peoples R China
1943-7684
null
7
1966;1989;1990;1994;1995;1996;1997;1998;1999;2000;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
8
Natl Engn Lab Efficient Utilizat Soil & Fertilize, Tai An 271018, Shandong, Peoples R China;Shandong Agr Univ, Coll Life Sci, Dept Microbiol, Tai An 271018, Shandong, Peoples R China
Phytopathology
Wang, Bing
AMER PHYTOPATHOLOGICAL SOC
(ANI);(isDDH);(PAI);,;16S;31;87-22;a;A.;accurate;acquired;all;AMCC400023;among;analyses;analysis;analyzed;and;ANI;areas;as;assay;at;average;back;based;be;between;biochemical;by;carried;caused;characteristics;China;clearly;close;cluster;collinearity;colonization;common;compared;complete;composition;conjectured;construction;contained;data;detection;determined;directly;disease;distinct;DNADNA;economic;experiment;formed;from;gene;genes;genome;genomes;had;Hebei;homologous;horizontal;hybridization;identified;identity;important;in;indicated;indirectly;instead;isDDH;island;isolated;it;least;level;losses;mapping;member;might;Morphological;most;nucleotide;obtain;occurs;of;on;or;out;PAI;paper;pathogen;pathogenicity;pathogens;phylogenetic;physiological;phytopathogen;phytotoxin;potato;potato-growing;potted;Province;radish;region;relationship;relationships;relatively;results;ribosomal;RNA;S.;same;scab;scabiei;scabs;seedling;separating;sequenced;series;serious;severe;silico;slice;soilborne;sp;species;spp.;status;strain;Streptomyces;structure;such;supported;synthetic;systematically;taxonomic;test;that;thaxtomin;the;there;this;time;to;toxicity-related;toxin;transfer;tree;tuber;two;verified;very;was;were;which;while;whole;whole-genome;with;worldwide
Natl Engn Lab Efficient Utilizat Soil & Fertilize;Shandong Agr Univ
Potato scab, a serious soilborne disease caused by Streptomyces spp., occurs in potato-growing areas worldwide and results in severe economic losses. In this paper, the pathogenicity of Streptomyces strain AMCC400023, isolated from potato scabs in Hebei Province, China, was verified systematically by the radish seedling test, the potato tuber slice assay, the potted back experiment, and the detection of phytotoxin thaxtomin A. Morphological, physiological, and biochemical characteristics were determined, and the 16S ribosomal RNA analyses of Streptomyces sp. AMCC400023 were carried out. To obtain the accurate taxonomic status of the pathogen strain, the whole genome was sequenced, and the phylogenetic tree among 31 Streptomyces genomes was formed. The average nucleotide identity (ANI) and in silico DNADNA hybridization (isDDH) were analyzed, and at the same time, the toxicity-related genes between Streptomyces sp. AMCC400023 and Streptomyces scabiei were compared, all based on the whole-genome level. All of the data supported that, instead of a member of S. scabiei, test strain Streptomyces sp. AMCC400023 was a distinct phytopathogen of potato common scab, which had a relatively close relationship with S. scabiei while separating clearly from S. scabiei at least in the species level of taxonomic status. The complete pathogenicity island (PAI) composition of Streptomyces sp. AMCC400023 was identified, which contained a toxin region and a colonization region. It was conjectured that the PAI of Streptomyces sp. AMCC400023 might be directly or indirectly acquired from S. scabiei 87-22 by horizontal gene transfer, or at the very least, there was a very close homologous relationship between the two pathogens as indicated by a series of analyses, such as phylogenetic relationships among 31 Streptomyces species, ANI and isDDH analyses, PAI structure mapping, thaxtomin A synthetic gene cluster tree construction, and most important, the collinearity analysis at the genome level.
JEZ-7925-2023;JHV-1750-2023;T-9297-2019
DNA-DNA HYBRIDIZATION;PHYLOGENETIC ANALYSIS;PHYTOTOXIN;PLANT PATHOGEN;POTATO;RIBOSOMAL-RNA GENES;SEQUENCE;SP-NOV;THAXTOMIN BIOSYNTHESIS;VIRULENCE
3
null
null
14
DNA-DNA HYBRIDIZATION;PHYLOGENETIC ANALYSIS;PHYTOTOXIN;plant pathogen;POTATO;RIBOSOMAL-RNA GENES;SEQUENCE;SP-NOV;THAXTOMIN BIOSYNTHESIS;VIRULENCE
WOS:000473667800003
Natl Engn Lab Efficient Utilizat Soil & Fertilize, Shandong, Peoples R China;Shandong Agr Univ, Shandong, Peoples R China;Shandong Plant Protect Stn, Shandong, Peoples R China
China
2,019
null
0000-0002-9771-0919;0000-0003-2746-350X
null
null
English
null
ADV MICROB PHYSIOL;AM J POTATO RES;ANNU REV PHYTOPATHOL;ANTON LEEUW INT J G;APPL ENVIRON MICROB;ARCH MICROBIOL;BIOINFORMATICS;BMC BIOINFORMATICS;BMC GENOMICS;FEMS MICROBIOL LETT;FEMS MICROBIOL REV;GENOME RES;INT J CURR MICROBIOL;INT J SYST BACTERIOL;INT J SYST EVOL MICR;J AGR FOOD CHEM;J ANTIBIOT;J APPL MICROBIOL;J BACTERIOL;J BIOL CHEM;J CHEM SOC CHEM COMM;J FOOD AGRIC ENVIRON;MICROBIOL MOL BIOL R;Mob Genet Elements;MOL MICROBIOL;MOL PLANT MICROBE IN;MOL PLANT PATHOL;NATURE;NUCL ACIDS;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PATHOG DIS;PHYSIOL MOL PLANT P;PHYTOPATHOLOGY;PLANT DIS;PLANT PATHOL;PLASMID;PLOS ONE;PLOS PATHOG;STAND GENOMIC SCI;SYST APPL MICROBIOL
He, Xiaoli;Liang, Feiyang;Lin, Rongshan;Shi, Chunyu;Wang, Bing;Xiao, Yunli;Yao, Yaqian;Zhang, Mingshuo;Zhou, Bo
2024-03-11 ER
[Anonymous];Abdel-Rahman, T M A;Auch, A F;Aziz, R K;Bender, C L;Bentley, S D;Bertram, R;Bignell, D R D;Bordeleau Eric;Bouchek-Mechiche, K;Braun, S;Bukhalid, R A;Bérdy, J;Chapleau, M;Dees, M W;Delcher, A L;Edgar, R C;Edwards, U;Eggers, C H;Goris, J;Goyer, C;Guo, Y P;Hao, J J;Healy, F G;Herbst, D A;Hodgson, D A;Huguet-Tapia, J C;Johnson, E G;Joshi, M;Joshi, M V;Kers, J A;King, R R;Kreuze, J F;Labeda, D P;Lambert, D H;Lawrence, C H;Leiminger, J;Leiner, R H;Lerat, S;Li, L;Loria, R;Mcclerklin, S A;Meier-Kolthoff, J P;Miyajima, K;Park, D H;Pertry, I;Punta M.;Richter, M;Seipke, R F;Shirling E. B.;Song, J;Spaepen, S;Stamatakis, A;Stegmann, E;Wach, M J;Wang, Y P;Wanner, L A;Zhang, Y C
IG2YY
Shandong, Peoples R China;Shandong, Peoples R China.
8
null
3
null
30,829,555
He, Xiaoli;Liang, Feiyang;Lin, Rongshan;Shi, Chunyu;Wang, Bing;Xiao, Yunli;Yao, Yaqian;Zhang, Mingshuo;Zhou, Bo
PHYTOPATHOLOGY
Shandong, Peoples R China
Santos-Moreno, J;Schaerli, Y
10.1021/acssynbio.9b00174
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
3w1cx6b4p6i3f6o5q4i5i3b44n3lzmp2z
A Framework for the Modular and Combinatorial Assembly of Synthetic Gene Circuits
Univ Lausanne
null
Santos-Moreno, J; Schaerli, Y (corresponding author), Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland.
null
Santos-Moreno, Javier;Schaerli, Yolanda
Biochemical Research Methods
Swiss National Science Foundation [31003A_175608]; Swiss National Science Foundation (SNF) [31003A_175608] Funding Source: Swiss National Science Foundation (SNF)
WOS
Santos-Moreno, J;Schaerli, Y
Univ Lausanne, Lausanne, Switzerland
8
a;and;Assembly;circuits;Combinatorial;for;Framework;gene;Modular;of;synthetic;the
1
Moreno, Javier Santos;Schaerli, Yolanda
AMER CHEMICAL SOC
Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland;Y (corresponding author), Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland
Article
Univ Lausanne
WASHINGTON
null
null
Univ Lausanne
Swiss National Science Foundation;Swiss National Science Foundation (SNF)
Santos-Moreno, J; Schaerli, Y (corresponding author), Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland.
1697
Santos-Moreno, Javier;Schaerli, Yolanda
36
1
476,957,300,025
Swiss National Science Foundation (SNF) [31003A_175608] Funding Source: Swiss National Science Foundation (SNF);Swiss National Science Foundation [31003A_175608]
Switzerland
ACS SYNTHETIC BIOLOGY
Switzerland
null
null
Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland
2161-5063
Santos-Moreno, J;Schaerli, Y
JUL
javier.santosmoreno@unil.ch;yolanda.schaerli@unil.ch
Combinatorial Assembly;synthetic gene circuits
2
J
Biochemistry & Molecular Biology
3-node networks;accurate assembly;approach;available;circuit construction process;CIRCUITS;cloning;Combinatorial Assembly;combinatorial circuit libraries;combinatorial library;constituent parts;CONSTRUCTION;costs;CRISPR;CRISPR-based double-inverter circuit;DNA;DNA assembly;Escherichia coli;fast;final circuit;first step;gene circuit;gene circuit construction;Gene circuits;Gibson assembly;individual intermediate plasmids;iterative design-build-test cycles;LIBRARIES;plasmids;regions;restriction enzymes;scheme;second Gibson assembly;second step;simple;single plasmid;specific sets;synthetic biology;synthetic gene circuits;TAGS;time;time-limiting step;transcriptional units;two-step;usefulness;widespread Gibson assembly method
Santos-Moreno, J
cloning;CONSTRUCTION;CRISPR;DNA;DNA assembly;gene circuit;Gibson assembly;LIBRARIES;Synthetic biology;TAGS
1691
[Santos-Moreno, Javier; Schaerli, Yolanda] Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland.
We thank Marc Garcia-Garcera for help with R language, and Florence Gauye and Leo Moser for excellent technical assistance. We also thank all Schaerli lab members for useful discussions, and Lance E. Keller for critical reading of the manuscript. This work was funded by Swiss National Science Foundation Grant 31003A_175608.
3-node networks;accurate assembly;approach;available;circuit construction process;circuits;combinatorial assembly;combinatorial circuit libraries;combinatorial library;constituent parts;costs;CRISPR-based double-inverter circuit;Escherichia coli;fast;final circuit;first step;gene circuit construction;gene circuits;Gibson assembly;individual intermediate plasmids;iterative design-build-test cycles;plasmids;regions;restriction enzymes;scheme;second Gibson assembly;second step;simple;single plasmid;specific sets;synthetic gene circuits;time;time-limiting step;transcriptional units;two-step;usefulness;widespread Gibson assembly method
10.1002/mbo3.753;10.1016/j.cell.2007.12.033;10.1016/j.cell.2013.02.022;10.1021/acssynbio.5b00147;10.1021/acssynbio.7b00111;10.1021/acssynbio.7b00122;10.1021/acssynbio.8b00060;10.1021/sb4001323;10.1038/nature19841;10.1038/nbt.2355;10.1038/nbt1172;10.1038/ncomms5905;10.1038/NMETH1010;10.1039/c2mb25483b;10.1042/BJ20081949;10.1093/nar/gkr1288;10.1093/nar/gkt605;10.1093/nar/gkt860;10.1093/nar/gkt915;10.1093/nar/gky1182;10.1101/cshperspect.a023812;10.1111/nph.15625;10.1126/science.1192272;10.1186/1754-1611-2-5;10.1186/1754-1611-7-13;10.1186/1754-1611-8-2;10.1371/journal.pone.0003647;10.1371/journal.pone.0006441;10.1371/journal.pone.0016765;10.15252/msb.20167449;[10.1038/NMETH.1318, 10.1038/nmeth.1318]
Univ Lausanne
Santos-Moreno, J;Schaerli, Y
Santos-Moreno, J: Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland
Moreno, Javier Santos;Schaerli, Yolanda
31003A_175608
31
null
Switzerland
Univ Lausanne
Santos-Moreno, Javier
Green Submitted, Green Accepted
CONSTRUCTION;CRISPR;DNA;LIBRARIES;TAGS
Santos-Moreno, Javier; Schaerli, Yolanda;
null
Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland
Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland
null
cloning;DNA assembly;Gene circuits;Gibson assembly;Synthetic biology
7
2006;2007;2008;2009;2010;2011;2012;2013;2014;2016;2017;2018;2019
11
Univ Lausanne, Dept Fundamental Microbiol, Biophore Bldg, CH-1015 Lausanne, Switzerland
ACS Synth. Biol.
Schaerli, Yolanda
AMER CHEMICAL SOC
,;3-node;a;accurate;allows;and;approach;are;assembling;assembly;associated;available;based;by;circuit;circuits;cloning;coli;combinatorial;commonly;constituent;constructed;construction;costs;CRISPR-based;cycles;demonstrate;design-build-test;digested;double-inverter;drive;efficient;emerge;enzymes;Escherichia;fast;final;first;flanking;for;framework;freely;from;gene;Gibson;have;here;hierarchical;in;individual;intermediate;into;involves;is;iterative;libraries;library;make;method;modular;most;networks;of;on;our;overlaps;parts;plasmid;plasmids;present;process;reduces;regions;restriction;resulting;scheme;second;sequencing;set;sets;simple;single;specific;step;substantially;synthetic;that;the;these;this;time;time-limiting;to;transcriptional;two-step;units;usefulness;we;widespread;with;yield
Univ Lausanne
Synthetic gene circuits emerge from iterative design-build-test cycles. Most commonly, the time-limiting step is the circuit construction process. Here, we present a hierarchical cloning scheme based on the widespread Gibson assembly method and make the set of constructed plasmids freely available. Our two-step modular cloning scheme allows for simple, fast, efficient, and accurate assembly of gene circuits and combinatorial circuit libraries in Escherichia coli. The first step involves Gibson assembly of transcriptional units from constituent parts into individual intermediate plasmids. In the second step, these plasmids are digested with specific sets of restriction enzymes. The resulting flanking regions have overlaps that drive a second Gibson assembly into a single plasmid to yield the final circuit. This approach substantially reduces time and sequencing costs associated with gene circuit construction and allows for modular and combinatorial assembly of circuits. We demonstrate the usefulness of our framework by assembling a CRISPR-based double-inverter circuit and a combinatorial library of 3-node networks.
AAH-9318-2019;T-8864-2017
CONSTRUCTION;CRISPR;DNA;LIBRARIES;TAG
3
null
cloning;DNA assembly;gene circuit;Gibson assembly;Synthetic biology
13
cloning;CONSTRUCTION;CRISPR;DNA;DNA assembly;Gene circuits;Gibson assembly;LIBRARIES;Synthetic biology;TAG
WOS:000476957300025
Univ Lausanne, Lausanne, Switzerland
Switzerland
2,019
null
0000-0001-6268-2623;0000-0002-9083-7343
null
null
English
null
ACS SYNTH BIOL;BIOCHEM J;CELL;CSH PERSPECT BIOL;J Biol Eng;MICROBIOLOGYOPEN;MOL BIOSYST;MOL SYST BIOL;NAT BIOTECHNOL;NAT COMMUN;NAT METHODS;NATURE;NEW PHYTOL;NUCLEIC ACIDS RES;PLOS ONE;SCIENCE
Santos-Moreno, Javier;Schaerli, Yolanda
2024-03-11 ER
Butzin, N C;Casini, A;Didovyk, A;Duarte, J M;Engler, C;Gibson, D G;Guye, P;Halleran, A D;Haurwitz, R E;Hughes, R A;Kahl, L J;Kogenaru, M;Li, M Z;Liu, X;Pereira, S B;Pollak, B;Potvin-Trottier, L;Pédelacq, J D;Qi, L;Qi, L S;Quan, J Y;Sakaue-Sawano, A;Schaerli, Y;Shcherbo, D;Shetty Reshma, P;Taylor, G M;Torella, J P;Weber, E;Zhang, Y W
IL0AB
Lausanne, Switzerland
13
null
1
null
31,185,158
Santos-Moreno, Javier;Schaerli, Yolanda
ACS SYNTH BIOL
Lausanne, Switzerland
Burley, G A;Padroni, G;Parkinson, J A;Reichenbach, L F;Taladriz-Sender, A;Withers, J M
10.1021/jacs.8b12444
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
3k383o6d1u2j29501t6lvk1o1s363166j5dq
Sequence-Selective Minor Groove Recognition of a DNA Duplex Containing Synthetic Genetic Components
Univ Strathclyde
null
Burley, GA (corresponding author), Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland.
null
Burley, Glenn A;Padroni, Giacomo;Parkinson, John A;Reichenbach, Linus F;Taladriz-Sender, Andrea;Withers, Jamie M
Chemistry, Multidisciplinary
University of Strathclyde studentship scheme; STFC [ST/M000125/1]; BBSRC [BB/R006857/1]; Leverhulme Trust [RPG-2018-149]; BBSRC [BB/R006857/1] Funding Source: UKRI; STFC [ST/M000125/1] Funding Source: UKRI
WOS
Burley, G A
Univ Strathclyde, Lanark, Scotland
141
a;Components;Containing;DNA;Duplex;genetic;Groove;Minor;of;recognition;sequence-Selective;synthetic
1
Burley, Glenn;Padroni, Giacomo;Parkinson, John Andrew;Taladriz-Sender, Andrea;Withers, Jamie
AMER CHEMICAL SOC
Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
Article
Univ Strathclyde
WASHINGTON
null
null
Univ Strathclyde
BBSRC;Leverhulme Trust;STFC;University of Strathclyde studentship scheme
Burley, GA (corresponding author), Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland.
9563
Burley, Glenn A;Padroni, Giacomo;Parkinson, John A;Reichenbach, Linus F;Taladriz-Sender, Andrea;Withers, Jamie M
27
1
471,835,600,023
BBSRC [BB/R006857/1];BBSRC [BB/R006857/1] Funding Source: UKRI;Leverhulme Trust [RPG-2018-149];STFC [ST/M000125/1];STFC [ST/M000125/1] Funding Source: UKRI;University of Strathclyde studentship scheme
UK
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
UK
null
null
Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
0002-7863
Burley, G A;Padroni, G;Parkinson, J A;Reichenbach, L F;Taladriz-Sender, A;Withers, J M
JUN 19
glenn.burley@strath.ac.uk
DNA Duplex;sequence-Selective Minor Groove Recognition;Synthetic Genetic Components
6
J
Chemistry
allosteric distortion;basis;BINDING;described;DNA;DNA Duplex;evolution;G.C pair;HAIRPIN POLYAMIDE;hairpin polyamides;hairpin pyrrole-imidazole polyamides;higher melting stabilization;imidazole unit;incorporation;influence minor groove recognition;major groove;minor groove;minor groove recognition;molecular determinants;NMR CHARACTERIZATION;NMR structural study;P nucleotide;P-Z-containing DNA duplex;P.Z pair;polyamide;PYRROLE-IMIDAZOLE POLYAMIDES;pyrrole-imidazole polyamides bind;reduced level;relative;RNA;sequence-Selective Minor Groove Recognition;site;stable complex;STRUCTURAL BASIS;structural hallmark;synthetic biology applications;synthetic genetic components;synthetic genetic information;SYSTEM;TRANSCRIPTION;two isolated P.Z pairs;UNNATURAL BASE-PAIR;unnatural base-pairs;unnatural P.Z base-pair;Watson-Crick base-pairs
Padroni, G
BINDING;EVOLUTION;HAIRPIN POLYAMIDE;NMR CHARACTERIZATION;PYRROLE-IMIDAZOLE POLYAMIDES;RNA;STRUCTURAL BASIS;SYSTEM;TRANSCRIPTION;UNNATURAL BASE-PAIR
9555
[Padroni, Giacomo; Withers, Jamie M.; Taladriz-Sender, Andrea; Reichenbach, Linus F.; Parkinson, John A.; Burley, Glenn A.] Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland.
This work was supported by the University of Strathclyde studentship scheme [G.P.], the STFC [ST/M000125/1], BBSRC [BB/R006857/1], and Leverhulme Trust [RPG-2018-149].
allosteric distortion;basis;binding;described;DNA;DNA duplex;G.C pair;hairpin polyamides;hairpin pyrrole-imidazole polyamides;higher melting stabilization;imidazole unit;incorporation;influence minor groove recognition;major groove;minor groove;minor groove recognition;molecular determinants;NMR structural study;P nucleotide;P-Z-containing DNA duplex;P.Z pair;polyamide;pyrrole-imidazole polyamides bind;reduced level;relative;site;stable complex;structural basis;structural hallmark;synthetic biology applications;synthetic genetic components;synthetic genetic information;two isolated P.Z pairs;unnatural base-pairs;unnatural P.Z base-pair;Watson-Crick base-pairs
10.1002/anie.200905173;10.1002/anie.201006735;10.1007/978-3-642-23394-4_33;10.1016/B978-0-12-409547-2.12561-2];10.1016/j.bmc.2018.01.026;10.1016/j.bpc.2004.06.001;10.1016/j.chempr.2016.11.009;10.1016/j.tet.2007.03.041;10.1016/j.tibs.2014.07.002;10.1016/S0079-6565(97)00023-X;10.1016/S0959-440X(03)00081-2;10.1021/acs.accounts.7b00403;10.1021/acs.biochem.6b00533;10.1021/acs.jpcb.6b00125;10.1021/acs.jpcb.7b00345;10.1021/acschembio.5b00952;10.1021/acssynbio.6b00224;10.1021/ar030287f;10.1021/ar200257x;10.1021/bi301327v;10.1021/bi400558c;10.1021/bi982628g;10.1021/ja00259a030;10.1021/ja0373622;10.1021/ja0744899;10.1021/ja105068b;10.1021/ja1072383;10.1021/ja204910n;10.1021/ja207907d;10.1021/ja3014924;10.1021/ja308888c;10.1021/ja408814g;10.1021/ja800888d;10.1021/ja901309z;10.1021/ja964314r;10.1021/ja971569b;10.1021/ja983671u;10.1021/jacs.5b02251;10.1021/jacs.5b03482;10.1021/jacs.7b03540;10.1021/jacs.8b05042;10.1021/sb500268n;10.1038/382559a0;10.1038/nbt.2556;10.1038/ncomms7706;10.1038/nmeth915;10.1038/srep01883;10.1039/c2cc36293g;10.1073/pnas.0509843102;10.1073/pnas.0704217104;10.1073/pnas.0906532106;10.1073/pnas.1222035110;10.1073/pnas.1311778111;10.1093/nar/29.3.693;10.1093/nar/gkl633;10.1093/nar/gkv638;10.1093/nar/gkw890;10.1093/nar/gkx1211;10.1093/nar/gkx144;10.1101/cshperspect.a023770;10.1126/science.7939719;10.1126/science.aan6414;10.1126/science.aat0971;10.1146/annurev-biochem-060408-091030;10.1186/s13637-016-0055-8;10.1358/dof.2001.026.01.858702;10.2174/1568011054222346
Univ Strathclyde
Burley, G A;Padroni, G;Parkinson, J A;Reichenbach, L F;Taladriz-Sender, A;Withers, J M
Padroni, G: Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
Burley, Glenn;Padroni, Giacomo;Taladriz-Sender, Andrea
BB/R006857/1;RPG-2018-149;ST/M000125/1
67
null
UK
Univ Strathclyde
Padroni, Giacomo
Green Accepted, hybrid
BINDING;EVOLUTION;HAIRPIN POLYAMIDE;NMR CHARACTERIZATION;PYRROLE-IMIDAZOLE POLYAMIDES;RNA;STRUCTURAL BASIS;SYSTEM;TRANSCRIPTION;UNNATURAL BASE-PAIR
Padroni, Giacomo; Withers, Jamie M.; Taladriz-Sender, Andrea; Reichenbach, Linus F.; Parkinson, John A.; Burley, Glenn A.;
null
Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
null
null
24
1987;1994;1996;1997;1998;1999;2001;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
11
Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
J. Am. Chem. Soc.
Burley, Glenn A
AMER CHEMICAL SOC
,;a;aligned;allosteric;an;and;applications;at;base-pair;base-pairs;basis;bind;binding;biology;by;complex;components;consisting;containing;described;determinants;develop;distortion;DNA;duplex;effectively;enlarges;entirely;for;form;further;G.C;genetic;groove;hairpin;hallmark;higher;imidazole;incorporation;induce;induced;influence;information;is;isolated;level;major;melting;mimicking;minor;molecular;narrows;NMR;nucleotide;of;P;P-Z-containing;P.Z;pair;pairs;polyamide;polyamides;provides;pyrrole-imidazole;recognition;reduced;relative;showed;site;slightly;stabilization;stable;structural;study;synthetic;that;the;this;to;two;understanding;unit;unnatural;Watson-Crick;when;with
Univ Strathclyde
The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P.Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P.Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P-Z-containing DNA duplex to form a stable complex, effectively mimicking a G.C pair. A structural hallmark of minor groove recognition of a P.Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.
AAV-8541-2021;ABC-2701-2021;HJY-7356-2023
BINDING;EVOLUTION;HAIRPIN POLYAMIDES;NMR CHARACTERIZATION;PYRROLE-IMIDAZOLE POLYAMIDES;RNA;STRUCTURAL BASIS;SYSTEM;TRANSCRIPTION;UNNATURAL BASE-PAIR
1
null
null
9
BINDING;EVOLUTION;HAIRPIN POLYAMIDES;NMR CHARACTERIZATION;PYRROLE-IMIDAZOLE POLYAMIDES;RNA;STRUCTURAL BASIS;SYSTEM;TRANSCRIPTION;UNNATURAL BASE-PAIR
WOS:000471835600023
Univ Strathclyde, Lanark, Scotland
UK
2,019
null
0000-0002-1406-4449;0000-0002-4896-113X;0000-0002-8274-4761;0000-0002-9746-9467;0000-0003-4270-6135
null
null
English
null
ACCOUNTS CHEM RES;ACS CHEM BIOL;ACS SYNTH BIOL;ANGEW CHEM INT EDIT;ANNU REV BIOCHEM;BIOCHEMISTRY-US;BIOORGAN MED CHEM;BIOPHYS CHEM;CHEM COMMUN;CHEM-US;CSH PERSPECT BIOL;CURR OPIN STRUC BIOL;Current Medicinal Chemistry - Anti-Cancer Agents;DRUG FUTURE;ENERGY AND ENVIRONMENTAL PERSPECTIVES;EURASIP J BIOINFORM;J AM CHEM SOC;J PHYS CHEM B;NAT BIOTECHNOL;NAT COMMUN;NAT METHODS;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PROG NUCL MAG RES SP;SCI REP-UK;SCIENCE;TETRAHEDRON;TRENDS BIOCHEM SCI
Burley, Glenn A;Padroni, Giacomo;Parkinson, John A;Reichenbach, Linus F;Taladriz-Sender, Andrea;Withers, Jamie M
2024-03-11 ER
Bando, T;Benner, S A;Biondi, E;Bostock-Smith, C E;Chawla, M;Chenoweth, D M;De Clairac, R P L;Declairac, R P L;Dervan Peter B.;Dervan, P B;Dose, C;Erwin, G S;Feldman, A W;Feldmann, A W;Geierstanger, B H;Georgiadis, M M;Hirao, I;Hiraoka, K;Hoshika, S;Hsu, C F;Ishizuka, T;James, P L;Kawamoto, Y;Kimoto, M;Krpetic, Z;Laos, R;Lavergne, T;Leal, N A;Li, L J;Meier, J L;Molt, R W;Nickols, N G;Ogundijo, O E;Padroni, G;Pandav, K;Panunto, T W;Pilch, D S;Puckett, J W;Ramakers, L A I;Reichenbach, L F;Rohs, R;Sefah, K;Seo, Y J;Sharma, S K;Slattery, M;Someya, T;Su, W;Trauger, J W;Wang, S;Wang, X Y;Warren, C L;White, S;Wijmenga, S S;Winiger, C B;Withers J.M.;Yang, F;Yang, Z Y;Zhang, L Q;Zhang, Q
ID7BB
Lanark, Scotland
14
null
1
null
31,117,639
Burley, Glenn A;Padroni, Giacomo;Parkinson, John A;Reichenbach, Linus F;Taladriz-Sender, Andrea;Withers, Jamie M
J AM CHEM SOC
Lanark, Scotland
Cho, G;Kwak, Y S
10.25387/g3.8030795
null
9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
6s3d4y6t3h1q3231725y2os2e6565lx3i2s
Evolution of Antibiotic Synthesis Gene Clusters in the <i>Streptomyces globisporus</i> TFH56, Isolated from Tomato Flower
Gyeongsang Natl Univ
null
Kwak, YS (corresponding author), Gyeongsang Natl Univ, 501 Jinju Daero, Jinju 52828, South Korea.
null
Cho, Gyeongjun;Kwak, Youn-Sig
Genetics & Heredity
Next-Generation BioGreen 21 Program [PJ013250]; Technology Development Program for Agriculture and Forestry, Ministry for Food, Agriculture, Forestry, and Fisheries, Republic of Korea [315004-5]
WOS
Kwak, Y S
Gyeongsang Natl Univ, Jinju, South Korea
9
,;<i>Streptomyces;Antibiotic;Clusters;evolution;Flower;From;gene;globisporus</i>;in;Isolated;of;synthesis;TFH56;the;Tomato
1
null
GENETICS SOCIETY AMERICA
Gyeongsang Natl Univ, 501 Jinju Daero, Jinju 52828, South Korea;Gyeongsang Natl Univ, Dept Plant Med, Inst Agr & Life Sci, Jinju 52828, South Korea;Gyeongsang Natl Univ, Div Appl Life Sci BK21Plus, Jinju 52828, South Korea
Article
Gyeongsang Natl Univ
BETHESDA
null
null
Gyeongsang Natl Univ
Next-Generation BioGreen 21 Program;Technology Development Program for Agriculture and Forestry, Ministry for Food, Agriculture, Forestry, and Fisheries, Republic of Korea
Kwak, YS (corresponding author), Gyeongsang Natl Univ, 501 Jinju Daero, Jinju 52828, South Korea.
1813
Cho, Gyeongjun;Kwak, Youn-Sig
5
2
535,489,600,003
Next-Generation BioGreen 21 Program [PJ013250];Technology Development Program for Agriculture and Forestry, Ministry for Food, Agriculture, Forestry, and Fisheries, Republic of Korea [315004-5]
South Korea
G3-GENES GENOMES GENETICS
South Korea
null
null
Gyeongsang Natl Univ, Div Appl Life Sci BK21Plus, Jinju 52828, South Korea
2160-1836
Cho, G;Kwak, Y S
JUN
kwak@gnu.ac.kr
<i>Streptomyces globisporus</i> TFH56;Antibiotic Synthesis Gene Clusters;evolution;Tomato Flower
2
J
Genetics & Heredity
<i>Streptomyces globisporus</i> TFH56;Antibiotic Synthesis Gene Clusters;average nucleotide identity;bioactive compound;bioactive metabolites;Botrytis cinerea;C-1027;caryolan-1-ol synthase gene;COMPLETE GENOME SEQUENCE;conprimycin synthetic gene cluster;evolution;genome;genome sequence;gray mold pathogen;lidamycin synthetic gene cluster;linear chromosome;linear plasmids;Pacific Biosciences RS II platform;plant diseases;S. globisporus;strain TFH56;Streptomyces complete genome;Streptomyces globisporus;streptomyces species;Streptomyces strain TFH56;study;three linear sequences (7.67 Mbp;Tomato Flower;total)
Cho, G
bioactive compound;C-1027;COMPLETE GENOME SEQUENCE;linear chromosome;Streptomyces complete genome
1807
[Cho, Gyeongjun; Kwak, Youn-Sig] Gyeongsang Natl Univ, Div Appl Life Sci BK21Plus, Jinju 52828, South Korea. [Kwak, Youn-Sig] Gyeongsang Natl Univ, Dept Plant Med, Inst Agr & Life Sci, Jinju 52828, South Korea.
This research was supported by the Next-Generation BioGreen 21 Program (PJ013250) and by the Technology Development Program for Agriculture and Forestry, Ministry for Food, Agriculture, Forestry, and Fisheries, Republic of Korea (project no. 315004-5).
average nucleotide identity;bioactive metabolites;Botrytis cinerea;caryolan-1-ol synthase gene;conprimycin synthetic gene cluster;genome;genome sequence;gray mold pathogen;lidamycin synthetic gene cluster;linear chromosome;linear plasmids;Pacific Biosciences RS II platform;plant diseases;S. globisporus;strain TFH56;Streptomyces globisporus;streptomyces species;Streptomyces strain TFH56;study;three linear sequences (7.67 Mbp;tomato flower;total)
10.1007/s10482-016-0824-0;10.1007/s41348-017-0090-z;10.1016/j.jbiotec.2016.02.004;10.1038/417141a;10.1038/ismej.2015.95;10.1038/nbt820;10.1038/srep08365;10.1098/rsob.170075;10.1099/mic.0.27758-0;10.1111/1574-6968.12128;10.1126/science.1072110;10.7164/antibiotics.41.1575;[10.1038/ja.2012.54, 10.1038/ja.2012.27];[10.1094/MPMI-05-18-0129-R, 10.1094/mpmi-05-18-0129-r]
Gyeongsang Natl Univ
Cho, G;Kwak, Y S
Cho, G: Gyeongsang Natl Univ, Div Appl Life Sci BK21Plus, Jinju 52828, South Korea
null
315004-5;PJ013250
15
null
South Korea
Gyeongsang Natl Univ
Cho, Gyeongjun
null
C-1027;COMPLETE GENOME SEQUENCE
Cho, Gyeongjun; Kwak, Youn-Sig;
null
Gyeongsang Natl Univ, Dept Plant Med, Inst Agr & Life Sci, Jinju 52828, South Korea;Gyeongsang Natl Univ, Div Appl Life Sci BK21Plus, Jinju 52828, South Korea
Gyeongsang Natl Univ, Dept Plant Med, Inst Agr & Life Sci, Jinju 52828, South Korea;Gyeongsang Natl Univ, Div Appl Life Sci BK21Plus, Jinju 52828, South Korea
null
Bioactive compounds;linear chromosome;Streptomyces complete genome
6
1988;2002;2003;2005;2008;2012;2013;2015;2016;2017;2018;2019
6
Gyeongsang Natl Univ, 501 Jinju Daero, Jinju 52828, South Korea
G3-Genes Genomes Genet.
Kwak, Youn-Sig
GENETICS SOCIETY AMERICA
(7.67;,;a;acquired;and;are;as;average;based;bioactive;Biosciences;Botrytis;can;caryolan-1-ol;chromosome;cinerea;classified;cluster;conprimycin;consistent;diseases;examples;flower;found;gene;genome;globisporus;gray;identity;II;in;included;inhibit;is;known;lidamycin;linear;Mbp;metabolites;mold;moreover;nucleotide;obtained;of;on;other;Pacific;pathogen;plant;plasmids;platform;presence;prevent;previously;produce;RS;S.;sequence;sequences;species;strain;Streptomyces;study;synthase;synthetic;TFH56;that;the;this;three;to;tomato;total);using;various;was;were;which;with
Gyeongsang Natl Univ
Streptomyces species are known to produce various bioactive metabolites that can prevent plant diseases. Previously, the Streptomyces strain TFH56 was found to inhibit the gray mold pathogen, Botrytis cinerea, in tomato flower. In this study, the genome sequence of strain TFH56 was acquired using the Pacific Biosciences RS II platform. Three linear sequences (7.67 Mbp in total) were obtained. Based on average nucleotide identity, strain TFH56 was classified as Streptomyces globisporus, which is consistent with the presence of a linear chromosome and linear plasmids. Moreover, as with other examples of S. globisporus, the genome of strain TFH56 included a caryolan-1-ol synthase gene, a conprimycin synthetic gene cluster, and a lidamycin synthetic gene cluster
null
C-1027;COMPLETE GENOME SEQUENCE
0
null
bioactive compound;linear chromosome;Streptomyces complete genome
7
BIOACTIVE COMPOUNDS;C-1027;COMPLETE GENOME SEQUENCE;linear chromosome;Streptomyces complete genome
WOS:000535489600003
Gyeongsang Natl Univ, Jinju, South Korea
South Korea
2,019
null
null
null
null
English
null
ANTON LEEUW INT J G;FEMS MICROBIOL LETT;Genus Streptomyces;ISME J;J ANTIBIOT;J BIOTECHNOL;J PLANT DIS PROTECT;MICROBIOL-SGM;MOL PLANT MICROBE IN;NAT BIOTECHNOL;NATURE;OPEN BIOL;SCI REP-UK;SCIENCE
Cho, Gyeongjun;Kwak, Youn-Sig
2024-03-11 ER
Bentley, S D;Brettin, T;Bérdy, J;Cha, J Y;Cho, G;Euzeby J. P.;Hu, J;Ikeda, H;Kim, D R;Kwon, Y;Labeda, D P;Li, X X;Liu, W;Taechowisan, T;Yagüe, P
LR1XG
Jinju, South Korea
6
null
1
null
31,018,944
Cho, Gyeongjun;Kwak, Youn-Sig
G3-GENES GENOM GENET
Jinju, South Korea
Ceroni, F;Nikolados, E M;Oyarzún, D A;Weiss, A Y
10.1021/acssynbio.8b00531
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
205j511e2m3h4h6c2g1g3m1v496j3m4n5d252f6b
Growth Defects and Loss-of-Function in Synthetic Gene Circuits
Univ Edinburgh
null
Oyarzún, DA (corresponding author), Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland.;Oyarzún, DA (corresponding author), Univ Edinburgh, Sch Informat, Edinburgh EH8 9AB, Midlothian, Scotland.;Oyarzún, DA (corresponding author), Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh EH9 3BF, Midlothian, Scotland.
null
Ceroni, Francesca;Nikolados, Evangelos-Marios;Oyarzun, Diego A;Weiss, Andrea Y
Biochemical Research Methods
null
WOS
Oyarzún, D A
Imperial Coll London, London, England;Univ Edinburgh, Midlothian, Scotland
8
and;circuits;Defects;gene;growth;in;Loss-of-Function;synthetic
1
Ceroni, Francesca;Nikolados, Evangelos-Marios
AMER CHEMICAL SOC
Imperial Coll London, Dept Chem Engn, London SW7 2AZ, England;Imperial Coll London, Hammersmith Hosp, Dept Med, London W12 0NN, England;Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England;Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland;Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland.; Oyarzún, DA (corresponding author), Univ Edinburgh, Sch Informat, Edinburgh EH8 9AB, Midlothian, Scotland.; Oyarzún, DA (corresponding author), Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh EH9 3BF, Midlothian, Scotland;Univ Edinburgh, Sch Informat, Edinburgh EH8 9AB, Midlothian, Scotland;Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh EH9 3BF, Midlothian, Scotland
Article
Univ Edinburgh
WASHINGTON
null
null
Imperial Coll London;Univ Edinburgh
null
Oyarzún, DA (corresponding author), Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland.; Oyarzún, DA (corresponding author), Univ Edinburgh, Sch Informat, Edinburgh EH8 9AB, Midlothian, Scotland.; Oyarzún, DA (corresponding author), Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh EH9 3BF, Midlothian, Scotland.
1240
Ceroni, Francesca;Nikolados, Evangelos-Marios;Oyarzun, Diego A;Weiss, Andrea Y
25
6
473,115,700,002
null
UK
ACS SYNTHETIC BIOLOGY
UK
null
null
Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland
2161-5063
Ceroni, F;Nikolados, E M;Oyarzún, D A;Weiss, A Y
JUN
d.oyarzun@ed.ac.uk
growth Defects;Loss-of-Function;synthetic gene circuits
4
J
Biochemistry & Molecular Biology
ALLOCATION;approach;bacterial gene circuits;break down circuit function;cellular burden;cellular capacity;cellular host;circuit output;complex relation;comprehensive framework;critical capacity;design space;DYNAMICS;endogenous processes;equilibrium;ESCHERICHIA-COLI;expense;expression;extensive simulations;extra load;Gene circuits;gene expression;genetic burden;genetic logic gates;growth;growth conditions;growth Defects;growth rate drop;heterologous genes;host;host-circuit interactions;IMPACT;integrated host-circuit models;large regions;leading;limit;Loss-of-Function;mechanistic modeling;MODEL;model-based design;NETWORK;optimization;physiology;point;protein output;reduced biosynthesis;resource allocation;result;ribosomal scarcity;RIBOSOMES;shape;silico;simulations;stronger induction;synthetic gene circuits;transcriptional logic gates;weak induction;wide-ranging implications
Nikolados, E M
ALLOCATION;DYNAMICS;ESCHERICHIA-COLI;EXPRESSION;genetic burden;genetic logic gates;host-circuit interactions;mechanistic modeling;MODEL;model-based design;NETWORK;RIBOSOMES;synthetic gene circuits
1231
[Nikolados, Evangelos-Marios; Oyarzun, Diego A.] Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland. [Weiss, Andrea Y.] Imperial Coll London, Hammersmith Hosp, Dept Med, London W12 0NN, England. [Ceroni, Francesca] Imperial Coll London, Dept Chem Engn, London SW7 2AZ, England. [Ceroni, Francesca] Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England. [Oyarzun, Diego A.] Univ Edinburgh, Sch Informat, Edinburgh EH8 9AB, Midlothian, Scotland. [Oyarzun, Diego A.] Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh EH9 3BF, Midlothian, Scotland.
null
approach;bacterial gene circuits;break down circuit function;cellular burden;cellular capacity;cellular host;circuit output;complex relation;comprehensive framework;critical capacity;design space;endogenous processes;equilibrium;expense;extensive simulations;extra load;gene circuits;gene expression;growth;growth conditions;growth defects;growth rate drop;heterologous genes;host;host-circuit interactions;impact;integrated host-circuit models;large regions;leading;limit;optimization;physiology;point;protein output;reduced biosynthesis;resource allocation;result;ribosomal scarcity;shape;silico;simulations;stronger induction;synthetic gene circuits;transcriptional logic gates;weak induction;wide-ranging implications
10.1002/biot.201200085;10.1006/jmbi.1993.1319;10.1007/s10295-018-2013-9;10.1016/j.bpj.2013.04.049;10.1016/j.bpj.2015.06.034;10.1016/j.bpj.2017.12.010;10.1016/j.cell.2012.05.044;10.1016/j.mib.2016.07.009;10.1021/acssynbio.6b00040;10.1021/acssynbio.6b00361;10.1021/acssynbio.7b00119;10.1021/acssynbio.8b00015;10.1021/sb400055h;10.1038/35002125;10.1038/35002131;10.1038/msb.2011.94;10.1038/msb4100204;10.1038/nbt.4238;10.1038/nchembio.218;10.1038/ncomms1516;10.1038/nmeth.4635;10.1038/s41467-018-02898-6;10.1038/s41467-018-03970-x;10.1038/s41564-017-0022-5;10.1073/pnas.1416533112;10.1073/pnas.1718622115;10.1093/nar/gkv1280;10.1103/PhysRevLett.108.018102;10.1126/science.1192588;10.1128/jb.177.6.1497-1504.1995;10.15252/msb.20167461;[10.1038/NMETH.3339, 10.1038/nmeth.3339]
Univ Edinburgh
Ceroni, F;Nikolados, E M;Oyarzún, D A;Weiss, A Y
Nikolados, E M: Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland
Ceroni, Francesca;Oyarzun, Diego A
null
32
null
UK
Imperial Coll London;Univ Edinburgh
Nikolados, Evangelos-Marios
Green Submitted, Green Accepted
ALLOCATION;DYNAMICS;ESCHERICHIA-COLI;EXPRESSION;MODEL;NETWORK;RIBOSOMES
Nikolados, Evangelos-Marios; Weiss, Andrea Y.; Ceroni, Francesca; Oyarzun, Diego A.;
null
Imperial Coll London, Dept Chem Engn, London SW7 2AZ, England;Imperial Coll London, Hammersmith Hosp, Dept Med, London W12 0NN, England;Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England;Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland;Univ Edinburgh, Sch Informat, Edinburgh EH8 9AB, Midlothian, Scotland;Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh EH9 3BF, Midlothian, Scotland
Imperial Coll London, Dept Chem Engn, London SW7 2AZ, England;Imperial Coll London, Hammersmith Hosp, Dept Med, London W12 0NN, England;Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England;Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland;Univ Edinburgh, Sch Informat, Edinburgh EH8 9AB, Midlothian, Scotland;Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh EH9 3BF, Midlothian, Scotland
null
host-circuit interactions;genetic burden;genetic logic gate;mechanistic models;model-based design;Synthetic gene circuit
6
1993;1995;2000;2008;2009;2010;2011;2012;2013;2015;2016;2017;2018
36
Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3BF, Midlothian, Scotland;Univ Edinburgh, Sch Informat, Edinburgh EH8 9AB, Midlothian, Scotland;Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh EH9 3BF, Midlothian, Scotland
ACS Synth. Biol.
Oyarzun, Diego A
AMER CHEMICAL SOC
,;a;across;allocation;and;approach;assess;at;bacterial;be;between;beyond;biosynthesis;both;break;built;burden;by;can;capacity;caused;cellular;circuit;circuits;complex;comprehensive;conditions;critical;defects;design;down;drop;endogenous;equilibrium;even;expense;expression;extensive;extent;extra;for;framework;function;gates;gene;genes;growth;here;heterologous;highlights;host;host-circuit;impact;implications;in;increased;induction;integrated;interactions;is;large;leading;limit;load;logic;models;of;offers;on;optimization;our;output;perturb;physiology;point;processes;protein;quantify;rate;reaches;reduced;regions;relation;resource;result;reveal;ribosomal;scarcity;shape;sharply;shifts;silico;simulations;slow;space;stronger;studied;suggest;synthetic;that;the;their;tipping;to;transcriptional;various;we;weak;which;wide-ranging;with;yet
Univ Edinburgh
Synthetic gene circuits perturb the physiology of their cellular host. The extra load on endogenous processes shifts the equilibrium of resource allocation in the host, leading to slow growth and reduced biosynthesis. Here we built integrated host-circuit models to quantify growth defects caused by synthetic gene circuits. Simulations reveal a complex relation between circuit output and cellular capacity for gene expression. For weak induction of heterologous genes, protein output can be increased at the expense of growth defects. Yet for stronger induction, cellular capacity reaches a tipping point, beyond which both gene expression and growth rate drop sharply. Extensive simulations across various growth conditions and large regions of the design space suggest that the critical capacity is a result of ribosomal scarcity. We studied the impact of growth defects on various gene circuits and transcriptional logic gates, which highlights the extent to which cellular burden can limit, shape, and even break down circuit function. Our approach offers a comprehensive framework to assess the impact of host-circuit interactions in silico, with wide-ranging implications for the design and optimization of bacterial gene circuits.
A-7945-2008;J-3835-2014
ALLOCATION;DYNAMICS;ESCHERICHIA-COLI;EXPRESSION;MODEL;NETWORKS;RIBOSOME
2
null
genetic burden;genetic logic gates;host-circuit interactions;mechanistic modeling;model-based design;synthetic gene circuits
19
ESCHERICHIA-COLI;ALLOCATION;host-circuit interactions;DYNAMICS;EXPRESSION;genetic burden;genetic logic gates;mechanistic models;MODEL;model-based design;NETWORKS;RIBOSOME;synthetic gene circuits
WOS:000473115700002
Imperial Coll London, London, England;Univ Edinburgh, Midlothian, Scotland
UK
2,019
null
0000-0001-7237-4982;0000-0003-2303-0889
null
null
English
null
ACS SYNTH BIOL;BIOPHYS J;BIOTECHNOL J;CELL;CURR OPIN MICROBIOL;J BACTERIOL;J IND MICROBIOL BIOT;J MOL BIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV LETT;SCIENCE
Ceroni, Francesca;Nikolados, Evangelos-Marios;Oyarzun, Diego A;Weiss, Andrea Y
2024-03-11 ER
Blanchard, A E;Borkowski, O;Cambray, G;Carbonell-Ballestero, M;Cardinale, S;Ceroni, F;Cookson, N A;Darlington, A P S;Del Vecchio, D;Dong, H J;Elowitz, M B;Gardner, T S;Gorochowski, T E;Gyorgy, A;Karr, J R;Liao, C;Liu, D;Mather, W H;Nyström, A;Qian, Y L;Rondelez, Y;Rugbjerg, P;Scott, M;Shopera, T;Sleight, S C;Tan, C;Vind, J;Wang, B J;Weisse, A Y
IF5IY
Midlothian, Scotland;Midlothian, Scotland.
39
null
2
null
31,181,895
Ceroni, Francesca;Nikolados, Evangelos-Marios;Oyarzun, Diego A;Weiss, Andrea Y
ACS SYNTH BIOL
London, England;Midlothian, Scotland
Holliger, P;Houlihan, G;Taylor, A I
10.1101/cshperspect.a032490
a032490
1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
5s1k67265x59266r3a4o2z2g2z1j5k115333u5u
Beyond DNA and RNA: The Expanding Toolbox of Synthetic Genetics
MRC
null
Holliger, P (corresponding author), MRC, Lab Mol Biol, Cambridge CB2 0QH, England.
null
Holliger, Philipp;Houlihan, Gillian;Taylor, Alexander I
Cell Biology
MRC [MC_U105178804] Funding Source: UKRI; Medical Research Council [MC_U105178804] Funding Source: Medline
WOS
Holliger, P
MRC, Cambridge, England
11
:;and;beyond;DNA;Expanding;Genetics;of;RNA;synthetic;the;Toolbox
1
null
COLD SPRING HARBOR LAB PRESS
MRC, Lab Mol Biol, Cambridge CB2 0QH, England
Article
MRC
COLD SPRING HARBOR
null
null
Lab Mol Biol;MRC
Medical Research Council;MRC
Holliger, P (corresponding author), MRC, Lab Mol Biol, Cambridge CB2 0QH, England.
null
Holliger, Philipp;Houlihan, Gillian;Taylor, Alexander I
42
1
470,086,600,002
Medical Research Council [MC_U105178804] Funding Source: Medline;MRC [MC_U105178804] Funding Source: UKRI
UK
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
UK
null
null
MRC, Lab Mol Biol, Cambridge CB2 0QH, England
1943-0264
Holliger, P;Houlihan, G;Taylor, A I
JUN
ph1@mrc-lmb.cam.ac.uk
DNA;Expanding Toolbox;RNA;Synthetic Genetics
3
J
Cell Biology
ability;ALPHABET EXPANSION;application;applications;APTAMERS;biotechnology;catalysts (ribozymes/ DNAzymes);central;development;directed evolution;DNA;DNAZYME;ENZYMATIC-SYNTHESIS;enzymes;evolution;Expanding Toolbox;functional structures;gives rise;INFORMATION;key enabling technology;life's origins;LIGANDS;ligands (aptamers);modern biology;molecular level;molecular medicine;nanostructures;natural nucleic acids;new field;nonnatural alternatives;nucleic acid chemical toolbox;POLYMERASE;PROPAGATION;range;remarkable physicochemical properties;repositories;reverse transcriptase engineering;review;RNA;SELECTION;supporting genetic information storage;synthetic genetics;SYSTEMATIC EVOLUTION;unique;WORLD;xeno nucleic acids (XNAs);XNA polymerase
Taylor, A I
ALPHABET EXPANSION;APTAMERS;directed evolution;DNAZYME;ENZYMATIC-SYNTHESIS;LIGANDS;POLYMERASE;SELECTION;SYSTEMATIC EVOLUTION;WORLD
null
[Taylor, Alexander I.; Houlihan, Gillian; Holliger, Philipp] MRC, Lab Mol Biol, Cambridge CB2 0QH, England.
null
ability;application;applications;aptamers;biotechnology;catalysts (ribozymes/ DNAzymes);central;development;DNA;enzymes;evolution;functional structures;gives rise;information;key enabling technology;life's origins;ligands (aptamers);modern biology;molecular level;molecular medicine;nanostructures;natural nucleic acids;new field;nonnatural alternatives;nucleic acid chemical toolbox;propagation;range;remarkable physicochemical properties;repositories;reverse transcriptase engineering;review;RNA;supporting genetic information storage;synthetic genetics;unique;xeno nucleic acids (XNAs);XNA polymerase
10.1002/anie.200701369;10.1002/anie.201508678;10.1002/cbdv.200900083;10.1002/cbic.201600136;10.1002/cncr.26730;10.1002/eji.201646450;10.1016/j.addr.2018.04.007;10.1016/j.biomaterials.2014.08.046;10.1016/j.biotechadv.2015.02.008;10.1016/j.cbpa.2004.10.003;10.1016/j.cbpa.2016.08.001;10.1016/j.chembiol.2004.10.017;10.1016/j.chembiol.2012.10.011;10.1016/j.copbio.2017.04.004;10.1016/j.copbio.2017.09.006;10.1016/j.drudis.2014.09.004;10.1016/j.jconrel.2016.10.015;10.1016/j.jmb.2006.06.050;10.1016/j.sbi.2016.01.009;10.1016/j.tibs.2016.04.010;10.1017/S0033583517000038;10.1021/ac400058z;10.1021/acs.accounts.7b00056;10.1021/acs.chemrev.6b00114;10.1021/cb800314v;10.1021/ja100710j;10.1021/ja993688s;10.1021/jacs.5b06696;10.1021/jacs.5b12647;10.1021/jacs.6b10767;10.1021/jacs.6b13132;10.1021/jacs.7b11488;10.1021/nn1024658;10.1038/emm.2016.44;10.1038/natrevmats.2017.68;10.1038/nature01185;10.1038/nature13900;10.1038/nature13982;10.1038/nbt.3765;10.1038/ncomms11235;10.1038/nprot.2015.104;10.1038/nprot.2018.023;10.1038/nrd.2016.199;10.1038/nrg1231;10.1038/nrg3978;10.1038/nrm.2017.77;10.1038/s41467-017-02014-0;10.1038/s41557-018-0008-9;10.1038/s41570017-0076;10.1039/c3sc50574j;10.1039/c7sc03747c;10.1039/c7sc04491g;10.1073/pnas.0408440102;10.1073/pnas.0704211104;10.1073/pnas.1120964109;10.1073/pnas.1610103113;10.1073/pnas.92.25.11509;10.1073/pnas.94.9.4262;10.1080/15476286.2016.1236173;10.1093/nar/gkv1472;10.1093/nar/gkw608;10.1093/nar/gkx368;10.1101/cshperspect.a023770;10.1126/science.1200752;10.1126/science.1217622;10.1126/science.1238149;10.1126/science.271.5257.1854;10.1126/science.284.5423.2118;10.1126/science.aaf5409;10.1146/annurev-cellbio-100616-060758;10.1371/journal.pone.0015004;10.1517/14712598.2015.1025048;10.1557/mrs.2017.276;10.3389/fchem.2016.00018;10.3390/biomedicines5030051;10.3390/cancers10010009;[10.1038/NCHEM.1241, 10.1038/nchem.1241];[10.1038/NCHEM.2493, 10.1038/nchem.2493];[10.1038/NCHEM.2517, 10.1038/nchem.2517];[10.1038/NCHEMBIO.277, 10.1038/nchembio.277];[10.1038/NNANO.2017.99, 10.1038/nnano.2017.99]
MRC
Holliger, P;Houlihan, G;Taylor, A I
Taylor, A I: MRC, Lab Mol Biol, Cambridge CB2 0QH, England
Houlihan, Gillian
MC_U105178804
82
null
UK
MRC
Taylor, Alexander I
Bronze, Green Published
ALPHABET EXPANSION;APTAMERS;DIRECTED EVOLUTION;DNAZYME;ENZYMATIC-SYNTHESIS;LIGANDS;POLYMERASE;SELECTION;SYSTEMATIC EVOLUTION;WORLD
Taylor, Alexander I.; Houlihan, Gillian; Holliger, Philipp;
null
MRC, Lab Mol Biol, Cambridge CB2 0QH, England
MRC, Lab Mol Biol, Cambridge CB2 0QH, England
null
null
6
1995;1996;1997;1999;2000;2002;2003;2004;2005;2006;2007;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
29
MRC, Lab Mol Biol, Cambridge CB2 0QH, England
Cold Spring Harbor Perspect. Biol.
Holliger, Philipp
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
";(aptamers);(ribozymes/;(XNAs);,;a;ability;acid;acids;also;alternatives;and;application;applications;aptamers;are;as;at;been;believed;biology;biotechnology;both;capable;catalysts;central;chemical;collectively;define;development;DNA;DNAzymes);enabling;engineering;enzymes;evolution;expand;field;for;form;functional;genetic;genetics;gives;have;however;in;information;is;key;level;life's;ligands;medicine;modern;molecular;nanostructures;natural;new;nonnatural;not;nucleic;of;origins;outline;physicochemical;polymerase;propagation;properties;range;remarkable;repositories;reverse;review;rise;RNA;seeks;storage;structures;such;summarize;supporting;synthetic;technology;termed;the;their;this;to;toolbox;transcriptase;unique;we;well;which;widely;xeno;XNA
MRC
The remarkable physicochemical properties of the natural nucleic acids, DNA and RNA, define modern biology at the molecular level and are widely believed to have been central to life's origins. However, their ability to form repositories of information as well as functional structures such as ligands (aptamers) and catalysts (ribozymes/ DNAzymes) is not unique. A range of nonnatural alternatives, collectively termed xeno nucleic acids (XNAs), are also capable of supporting genetic information storage and propagation as well as evolution. This gives rise to a new field of "synthetic genetics," which seeks to expand the nucleic acid chemical toolbox for applications in both biotechnology and molecular medicine. In this review, we outline XNA polymerase and reverse transcriptase engineering as a key enabling technology and summarize the application of "synthetic genetics" to the development of aptamers, enzymes, and nanostructures.
Y-6197-2019
ALPHABET EXPANSION;APTAMERS;DIRECTED EVOLUTION;DNAZYME;ENZYMATIC-SYNTHESIS;LIGANDS;POLYMERASE;SELECTION;SYSTEMATIC EVOLUTION;WORLD
4
null
null
15
ALPHABET EXPANSION;aptamer;directed evolution;DNAZYME;ENZYMATIC-SYNTHESIS;LIGANDS;POLYMERASE;SELECTION;SYSTEMATIC EVOLUTION;WORLD
WOS:000470086600002
MRC, Cambridge, England
UK
2,019
null
null
null
null
English
null
ACCOUNTS CHEM RES;ACS CHEM BIOL;ACS NANO;ADV DRUG DELIVER REV;ANAL CHEM;ANGEW CHEM INT EDIT;ANNU REV CELL DEV BI;BIOMATERIALS;BIOMEDICINES;BIOTECHNOL ADV;CANCER-AM CANCER SOC;CANCERS;CHEM BIODIVERS;CHEM BIOL;CHEM REV;CHEM SCI;CHEMBIOCHEM;CSH PERSPECT BIOL;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;CURR OPIN STRUC BIOL;DRUG DISCOV TODAY;EUR J IMMUNOL;EXP MOL MED;EXPERT OPIN BIOL TH;FRONT CHEM;J AM CHEM SOC;J CONTROL RELEASE;J MOL BIOL;MRS BULL;NAT BIOTECHNOL;NAT CHEM;NAT CHEM BIOL;NAT COMMUN;NAT NANOTECHNOL;NAT PROTOC;NAT REV CHEM;NAT REV DRUG DISCOV;NAT REV GENET;NAT REV MATER;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;Q REV BIOPHYS;RNA BIOL;SCIENCE;TRENDS BIOCHEM SCI
Holliger, Philipp;Houlihan, Gillian;Taylor, Alexander I
2024-03-11 ER
Anosova, I;Attwater, J;Benner, S A;Burmeister, P E;Chaput, J C;Chen, T;Chen, T J;Chen, Z;Chim, N;Cozens, C;Darmostuk, M;Dellafiore, M A;Dunn, M R;Ellefson, J W;Eschenmoser, A;Feldman, A W;Fokina, A A;Friedman, A D;Garn, H;Gelinas, A D;Gold, L;Gothelf, K V;Grosjean, H;Herdewijn, P;Hori, S;Horning, D P;Houlihan, G;Howorka, S;Jo, H;Joyce, G F;Kasahara, Y;Khvorova, A;Kim, K R;Koide, S;Larsen, A C;Ledbetter, M P;Lee, K H;Lipi, F;Liu, J;Liu, Z X;Lutz, J F;Matsunaga, K;Mei, H;Meyer, K D;Mi, J;Morrow, P K;Ong, J L;Pan, W H;Pfeiffer, F;Pinheiro, V B;Reader, J S;Röthlisberger, P;Sacerdote, M G;Santoro, S W;Schimmel, P;Schumacher, T N M;Sczepanski, J T;Seeman, N C;Silverman, S K;Szathmáry, E;Tawiah, K D;Taylor, A I;Thirunavukarasu, D;Tsai, C H;Vater, A;Wachowius, F;Wang, Y J;Wang, Z M;Weigele, P;Wittrup, A;Wochner, A;Young, D D;Yu, H Y;Zhou, C;Zhou, J H
IB2GB
Cambridge, England
30
null
1
null
31,160,351
Holliger, Philipp;Houlihan, Gillian;Taylor, Alexander I
CSH PERSPECT BIOL
Cambridge, England
Boedicker, J;Chavez, M S;Chellamuthu, P;El-Naggar, M Y;Naughton, K;Pirbadian, S;Silva, K P T
10.3389/fmicb.2019.00938
938
AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
3g3c1n2y4zd1r4l5q64m105r4o3t1u5s703y4r
Biogenic Control of Manganese Doping in Zinc Sulfide Nanomaterial Using <i>Shewanella oneidensis</i> MR-1
Univ Southern Calif
null
Boedicker, J (corresponding author), Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA.;Boedicker, J (corresponding author), Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA.
null
Boedicker, James;Chavez, Marko S;Chellamuthu, Prithiviraj;El-Naggar, Mohamed Y;Naughton, Kyle;Pirbadian, Sahand;Silva, Kalinga Pavan T
Microbiology
Office of Naval Research [N00014-15-1-2573]; Office of Naval Research Multidisciplinary University Research Initiative [N00014-18-1-2632]; Air Force Office of Scientific Research Award [FA9550-14-1-0294]
WOS
Boedicker, J
Univ Southern Calif, Los Angeles, CA USA
10
<i>Shewanella;biogenic;control;Doping;in;Manganese;MR-1;Nanomaterial;of;oneidensis</i>;Sulfide;using;Zinc
1
Pirbadian, Sahand
FRONTIERS MEDIA SA
Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA;Univ Southern Calif, Dept Chem, Los Angeles, CA USA;Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA;Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA.; Boedicker, J (corresponding author), Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA
Article
Univ Southern Calif
LAUSANNE
null
null
Univ Southern Calif
Air Force Office of Scientific Research Award;Office of Naval Research;Office of Naval Research Multidisciplinary University Research Initiative
Boedicker, J (corresponding author), Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA.; Boedicker, J (corresponding author), Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA.
null
Boedicker, James;Chavez, Marko S;Chellamuthu, Prithiviraj;El-Naggar, Mohamed Y;Naughton, Kyle;Pirbadian, Sahand;Silva, Kalinga Pavan T
48
3
467,034,500,001
Air Force Office of Scientific Research Award [FA9550-14-1-0294];Office of Naval Research [N00014-15-1-2573];Office of Naval Research Multidisciplinary University Research Initiative [N00014-18-1-2632]
USA
FRONTIERS IN MICROBIOLOGY
USA;USA.;
null
null
Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA
1664-302X
Boedicker, J;Chavez, M S;Chellamuthu, P;El-Naggar, M Y;Naughton, K;Pirbadian, S;Silva, K P T
MAY 7
boedicke@usc.edu
<i>Shewanella oneidensis</i> MR-1;biogenic Control;Manganese;Zinc Sulfide Nanomaterial
7
J
Microbiology
<i>Shewanella oneidensis</i> MR-1;atom-by-atom nanomaterial synthesis;BACTERIA;biogenic;biogenic Control;biogenic quantum dots;biogenically;biological strategies;biological systems;compounds;cytochrome complex MtrCAB;cytochrome expression levels;dopant incorporation;expression;genetic control circuits;genetic engineering;inducer molecule;inducible expression;inorganic materials;interest;Manganese;manganese (KO oxide;manganese doped zinc sulfide nanoparticles (Mn;metals;microbes;MN;NANOCRYSTALS;nanomaterial characteristics;nanomaterials;nanoparticle (NP);NANOPARTICLES;natural synthetic capabilities;optical properties;OPTICAL-PROPERTIES;optoelectronic properties;particles;PHOTOLUMINESCENCE;precise modulation;promise;quantum dot (QD);recent advancements;redox state;reduction;results;semiconductor nanomaterials;shape;Shewanella;Shewanella oneindensis;similar;size;STRAIN;synthetic biology;Synthetic gene circuit;synthetic gene circuits;tunable control;Zinc Sulfide Nanomaterial;ZnS)
Chellamuthu, P
biogenic;EXPRESSION;genetic engineering;METALS;MN;NANOCRYSTALS;nanoparticle (NP);NANOPARTICLES;OPTICAL-PROPERTIES;PHOTOLUMINESCENCE;quantum dot (QD);REDUCTION;Shewanella;Synthetic biology
null
[Chellamuthu, Prithiviraj; Naughton, Kyle; Pirbadian, Sahand; Silva, Kalinga Pavan T.; Chavez, Marko S.; El-Naggar, Mohamed Y.; Boedicker, James] Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA. [Chellamuthu, Prithiviraj; El-Naggar, Mohamed Y.; Boedicker, James] Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA. [El-Naggar, Mohamed Y.] Univ Southern Calif, Dept Chem, Los Angeles, CA USA.
This work was supported by Office of Naval Research award number N00014-15-1-2573 and by the Office of Naval Research Multidisciplinary University Research Initiative Grant No. N00014-18-1-2632. SP was supported by Air Force Office of Scientific Research Award No. FA9550-14-1-0294. We thank USC Center for Electron Microscopy and Microanalysis (CEMMA) and California Institute of Technology GPS Division Analytical Facility for their help with sample analysis.
atom-by-atom nanomaterial synthesis;bacteria;biogenic quantum dots;biogenically;biological strategies;biological systems;compounds;cytochrome complex MtrCAB;cytochrome expression levels;dopant incorporation;genetic control circuits;inducer molecule;inducible expression;inorganic materials;interest;manganese (KO oxide;manganese doped zinc sulfide nanoparticles (Mn;microbes;nanomaterial characteristics;nanomaterials;natural synthetic capabilities;optical properties;optoelectronic properties;particles;precise modulation;promise;recent advancements;redox state;reduction;results;semiconductor nanomaterials;shape;Shewanella oneindensis;similar;size;strain;synthetic biology;synthetic gene circuit;synthetic gene circuits;tunable control;ZnS)
10.1002/adfm.200600163;10.1002/adfm.200600493;10.1002/bio.2801;10.1002/jctb.3934;10.1002/pssb.2221360155;10.1007/BF01569900;10.1007/BF02651190;10.1007/s00203-002-0472-9;10.1007/s00253-016-7756-5;10.1007/s10529-015-2026-7;10.1007/s13204-011-0036-x;10.1016/0022-2313(92)90034-7;10.1016/j.apsusc.2008.04.002;10.1016/j.apt.2012.09.007;10.1016/j.colsurfb.2011.02.030;10.1016/j.jallcom.2009.07.097;10.1016/j.jcis.2015.01.022;10.1016/j.optmat.2005.10.003;10.1016/j.pmatsci.2010.10.001;10.1016/j.spmi.2015.07.043;10.1016/j.stam.2005.03.006;10.1016/j.tim.2010.06.007;10.1016/S0168-6445(03)00044-5;10.1021/acssynbio.6b00349;10.1021/ar9001069;10.1021/ja110996c;10.1021/jz402495h;10.1021/sb4000564;10.1023/A:1020518818647;10.1038/nbt.4111;10.1038/nmat758;10.1038/nrmicro.2015.24;10.1038/nrmicro1947;10.1039/c2cs35331h;10.1063/1.1633347;10.1063/1.2711709;10.1063/1.328642;10.1073/pnas.0832310100;10.1073/pnas.1523633113;10.1080/15533170500471417;10.1103/PhysRevLett.72.416;10.1111/1751-7915.12297;10.1111/j.1365-2958.2010.07266.x;10.1128/AEM.01087-07;10.1128/AEM.50.2.491-497.1985;10.1128/AEM.67.1.260-269.2001;10.1128/AEM.71.8.4935-4937.2005;10.1186/s40643-017-0181-5;10.1371/journal.pone.0106937;10.3389/fmicb.2012.00056;10.3762/bjnano.6.181;10.4236/OJBIPHY.2016.61001, 10.4236/ojbiphy.2016.61001];[10.1007/s11051-006-9183-5, 10.1007/sl1051-006-9183-5];[10.1038/NMAT3912, 10.1038/nmat3912];[10.1039/c6ra13835g, 10.1039/C6RA13835G];[10.1039/c7ee00282c, 10.1039/C7EE00282C]
Univ Southern Calif
Boedicker, J;Chavez, M S;Chellamuthu, P;El-Naggar, M Y;Naughton, K;Pirbadian, S;Silva, K P T
Chellamuthu, P: Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA
null
FA9550-14-1-0294;N00014-15-1-2573;N00014-18-1-2632
58
null
USA
Univ Southern Calif
Chellamuthu, Prithiviraj
gold, Green Published
EXPRESSION;METALS;MN;NANOCRYSTALS;NANOPARTICLES;OPTICAL-PROPERTIES;PHOTOLUMINESCENCE;REDUCTION;SYNTHETIC BIOLOGY
Chellamuthu, Prithiviraj; Naughton, Kyle; Pirbadian, Sahand; Silva, Kalinga Pavan T.; Chavez, Marko S.; El-Naggar, Mohamed Y.; Boedicker, James;
null
Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA;Univ Southern Calif, Dept Chem, Los Angeles, CA USA;Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA
Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA;Univ Southern Calif, Dept Chem, Los Angeles, CA USA;Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA
null
biogenic;genetic engineering;nanoparticle (NP);quantum dot (QD);Shewanella
null
1979;1981;1985;1986;1992;1994;1995;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
12
Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA;Univ Southern Calif, Dept Phys & Astron, Los Angeles, CA 90007 USA
Front. Microbiol.
Boedicker, James
FRONTIERS MEDIA SA
(KO;(Mn;,;:;a;advancements;alter;an;and;as;assembled;atom-by-atom;bacteria;biogenic;biogenically;biological;biology;by;capabilities;characteristics;chemically;circuit;circuits;combine;complex;compounds;control;controlled;create;cytochrome;demonstrate;dopant;doped;dots;enabled;engineered;expression;for;gene;genetic;have;here;implementing;in;incorporation;inducer;inducible;inorganic;interest;into;levels;made;manganese;manufacture;many;materials;microbes;modulation;molecule;MtrCAB;nanomaterial;nanomaterials;nanoparticles;natural;naturally;of;oneindensis;optical;optoelectronic;our;oxide;particles;perform;physical;precise;promise;properties;quantum;recent;redox;reduction;regulated;results;semiconductor;shape;Shewanella;similar;size;specify;spurred;state;strain;strategies;such;sulfide;synthesis;synthesized;synthetic;systems;the;thereby;these;to;toward;tunable;using;we;were;which;with;zinc;ZnS)
Univ Southern Calif
Bacteria naturally alter the redox state of many compounds and perform atom-by-atom nanomaterial synthesis to create many inorganic materials. Recent advancements in synthetic biology have spurred interest in using biological systems to manufacture nanomaterials, implementing biological strategies to specify the nanomaterial characteristics such as size, shape, and optical properties. Here, we combine the natural synthetic capabilities of microbes with engineered genetic control circuits toward biogenically synthesized semiconductor nanomaterials. Using an engineered strain of Shewanella oneindensis with inducible expression of the cytochrome complex MtrCAB, we control the reduction of manganese (KO oxide. Cytochrome expression levels were regulated using an inducer molecule, which enabled precise modulation of dopant incorporation into manganese doped zinc sulfide nanoparticles (Mn:ZnS). Thereby, a synthetic gene circuit controlled the optical properties of biogenic quantum dots. These biogenically assembled nanomaterials have similar physical and optoelectronic properties to chemically synthesized particles. Our results demonstrate the promise of implementing synthetic gene circuits for tunable control of nanomaterials made by biological systems.
null
EXPRESSION;METALS;MN;NANOCRYSTALS;NANOPARTICLES;OPTICAL-PROPERTIES;PHOTOLUMINESCENCE;REDUCTION;SYNTHETIC BIOLOGY
4
null
biogenic;genetic engineering;nanoparticle (NP);quantum dot (QD);Shewanella
10
biogenic;EXPRESSION;genetic engineering;METALS;MN;NANOCRYSTALS;NANOPARTICLES;nanoparticle (NP);OPTICAL-PROPERTIES;PHOTOLUMINESCENCE;quantum dot (QD);REDUCTION;Shewanella;Synthetic biology
WOS:000467034500001
Univ Southern Calif, Los Angeles, CA USA
USA
2,019
null
0000-0002-4186-3457
null
null
English
null
ACCOUNTS CHEM RES;ACS SYNTH BIOL;ADV FUNCT MATER;ADV POWDER TECHNOL;ANTON LEEUW INT J G;APPL ENVIRON MICROB;APPL MICROBIOL BIOT;APPL NANOSCI;APPL PHYS LETT;APPL SURF SCI;ARCH MICROBIOL;BEILSTEIN J NANOTECH;BIORESOUR BIOPROCESS;BIOTECHNOL LETT;CHEM SOC REV;COLLOID SURFACE B;ENERG ENVIRON SCI;FEMS MICROBIOL REV;FRONT MICROBIOL;J ALLOY COMPD;J AM CHEM SOC;J APPL PHYS;J CHEM TECHNOL BIOT;J COLLOID INTERF SCI;J ELECTRON MATER;J IND MICROBIOL;J LUMIN;J NANOPART RES;J PHYS CHEM LETT;LUMINESCENCE;METAL CYCLING BACTER;MICROB BIOTECHNOL;MOL MICROBIOL;NAT BIOTECHNOL;NAT MATER;NAT REV MICROBIOL;OPEN J BIOPHYSICS;OPT MATER;P NATL ACAD SCI USA;PHYS REV LETT;PHYS STATUS SOLIDI B;PLOS ONE;PROG MATER SCI;RSC ADV;SCI TECHNOL ADV MAT;SUPERLATTICE MICROST;SYNTH REACT INORG M;THESIS;TRENDS MICROBIOL
Boedicker, James;Chavez, Marko S;Chellamuthu, Prithiviraj;El-Naggar, Mohamed Y;Naughton, Kyle;Pirbadian, Sahand;Silva, Kalinga Pavan T
2024-03-11 ER
Akid, R;Ali I.M.;Ang, J;Beerman P. A., G;Begum, R;Bhargava, R N;Biswas, S;Bouhenni, R;Bretschger, O;Burdige, D J;Cao, J;Chandrakar, R K;Chen, A Y;Coursolle, D;Da Costa, J P;Deng, Z T;Dunleavy, R;Fang, X S;Francis, C A;Fredrickson, J K;Goede, O;Hazra, C;Hurd, J M;Hussain, I;Jacob, J M;Karar, N;Katiyar, M;Kershaw, S V;Kole, A K;Komada, S;Lloyd, J R;Mao, C B;Marusak, K E;Myers, J M;Naik, R R;Nealson K.;Nealson, K H;Peng, W Q;Rodrigues, L R;Rodríguez-Carmona, E;Sasakura, H;Schuergers, N;Segall-Shapiro, T H;Singh, B N;Singh, B R;Smanski, M J;Smith, A M;Son, D;Spoerke, E D;Stroyuk, A L;Vance, M E;Wakatsuki, T;Wanjari, L;Warad, H C;West, E A;Wu, J W;Xiao, Q
HW9TV
Los Angeles, CA USA;Los Angeles, CA USA.
15
null
1
null
31,134,005
Boedicker, James;Chavez, Marko S;Chellamuthu, Prithiviraj;El-Naggar, Mohamed Y;Naughton, Kyle;Pirbadian, Sahand;Silva, Kalinga Pavan T
FRONT MICROBIOL
Los Angeles, CA USA
Bhatia, S K;Choi, T R;Gurav, R;Jung, H R;Ko, B J;Lee, J H;Moon, Y M;Park, J Y;Park, Y L;Song, H S;Yang, S Y;Yang, Y H
10.4014/jmb.1901.01070
null
KOREA SCI TECHNOL CENTER #402, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL, SOUTH KOREA
2f4p196e4o3j1a3b2s344r103x5a973596v6v5e
Increased Tolerance to Furfural by Introduction of Polyhydroxybutyrate Synthetic Genes to <i>Escherichia coli</i>
Konkuk Univ
null
Yang, YH (corresponding author), Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea.;Yang, YH (corresponding author), Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea.
null
Bhatia, Shashi Kant;Choi, Tae-Rim;Gurav, Ranjit;Jung, Hye-Rim;Ko, Byoung Joon;Lee, Ju-Hee;Moon, Yu-Mi;Park, Jun Young;Park, Ye Lim;Song, Hun-Suk;Yang, Soo-Yeon;Yang, Yung-Hun
Biotechnology & Applied Microbiology;Microbiology
Research Program for Solving Social Issues of the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2017M3A9E4077234]; National Research Foundation of Korea (NRF) [NRF-2015M1A5A1037196, NRF2016R1D1A1B03932301]; Polar Academic Program (PAP) [PE18900]
WOS
Yang, Y H
Konkuk Univ, Seoul, South Korea;Osong Med Innovat Fdn, Cheongju, South Korea
29
<i>Escherichia;by;coli</i>;Furfural;genes;increased;Introduction;of;Polyhydroxybutyrate;synthetic;to;Tolerance
1
Bhatia, Shashi;Gurav, Ranjit G;Ko, Byoung Joon
KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY
Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea;Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea.; Yang, YH (corresponding author), Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea;Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea;Osong Med Innovat Fdn, New Drug Dev Ctr, Cheongju 28160, South Korea
Article
Konkuk Univ
SEOUL
null
null
Konkuk Univ;Osong Med Innovat Fdn
National Research Foundation of Korea (NRF);Polar Academic Program (PAP);Research Program for Solving Social Issues of the National Research Foundation of Korea (NRF) - Ministry of Science and ICT
Yang, YH (corresponding author), Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea.; Yang, YH (corresponding author), Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea.
784
Bhatia, Shashi Kant;Choi, Tae-Rim;Gurav, Ranjit;Jung, Hye-Rim;Ko, Byoung Joon;Lee, Ju-Hee;Moon, Yu-Mi;Park, Jun Young;Park, Ye Lim;Song, Hun-Suk;Yang, Soo-Yeon;Yang, Yung-Hun
30
3
469,201,000,012
National Research Foundation of Korea (NRF) [NRF-2015M1A5A1037196, NRF2016R1D1A1B03932301];Polar Academic Program (PAP) [PE18900];Research Program for Solving Social Issues of the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2017M3A9E4077234]
South Korea
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
South Korea;South Korea.;
null
null
Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea
1017-7825
Bhatia, S K;Choi, T R;Gurav, R;Jung, H R;Ko, B J;Lee, J H;Moon, Y M;Park, J Y;Park, Y L;Song, H S;Yang, S Y;Yang, Y H
MAY
seokor@konkuk.ac.kr
<i>Escherichia coli</i>;Furfural;increased Tolerance;Introduction;Polyhydroxybutyrate Synthetic Genes
12
J
Biotechnology & Applied Microbiology;Microbiology
3-HYDROXYVALERATE;4-hydroxybenzaldehyde;<i>Escherichia coli</i>;absence;application;BACTERIA;bio-based;biodegradable polymer;BIOMASS HYDROLYSATE;compound;cost-effective PHB production;E. coli;Escherichia coli;feasibility;FERMENTATION;fermentative production;findings;furfural;glucose;good target product;growth;increased PHB production;increased Tolerance;INHIBITORS;innovative strategy;Introduction;lignocellulose hydrolysate;lignocellulose hydrolysates;mechanisms;non-edible resource;Overexpression;petroleum-based plastics;phaB;phaC;PHB;PHB production;PHB synthetic genes;PHB synthetic genes (bktB;POLY-3-HYDROXYBUTYRATE;POLYHYDROXYALKANOATES;Polyhydroxybutyrate;polyhydroxybutyrate (PHB);Polyhydroxybutyrate Synthetic Genes;potential;pretreatment processes;promising substrate;Ralstonia eutropha H16) improved cell growth;recombinant E. coli;resistance;results;study;sustainable;vanillin;well-known polyhydroxyalkanoate
Jung, H R
3-HYDROXYVALERATE;BACTERIA;BIOMASS HYDROLYSATE;Escherichia coli;FERMENTATION;furfural;GROWTH;INHIBITORS;lignocellulose hydrolysate;MECHANISMS;Overexpression;POLY-3-HYDROXYBUTYRATE;POLYHYDROXYALKANOATES;Polyhydroxybutyrate;resistance
776
[Jung, Hye-Rim; Lee, Ju-Hee; Moon, Yu-Mi; Choi, Tae-Rim; Yang, Soo-Yeon; Song, Hun-Suk; Park, Jun Young; Park, Ye Lim; Bhatia, Shashi Kant; Gurav, Ranjit; Yang, Yung-Hun] Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea. [Bhatia, Shashi Kant; Yang, Yung-Hun] Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea. [Ko, Byoung Joon] Osong Med Innovat Fdn, New Drug Dev Ctr, Cheongju 28160, South Korea.
This study was supported by the Research Program for Solving Social Issues of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2017M3A9E4077234), National Research Foundation of Korea (NRF) (NRF-2015M1A5A1037196, NRF2016R1D1A1B03932301). Consulting service from the Microbial Carbohydrate Resource Bank (MCRB, Seoul, Korea) was kindly appreciated. This work was also supported by the Polar Academic Program (PAP, PE18900).
4-hydroxybenzaldehyde;absence;application;bio-based;biodegradable polymer;compound;cost-effective PHB production;E. coli;feasibility;fermentative production;findings;furfural;glucose;good target product;increased PHB production;inhibitors;innovative strategy;introduction;lignocellulose hydrolysate;lignocellulose hydrolysates;non-edible resource;petroleum-based plastics;phaB;phaC;PHB;PHB production;PHB synthetic genes;PHB synthetic genes (bktB;polyhydroxybutyrate (PHB);potential;pretreatment processes;promising substrate;Ralstonia eutropha H16) improved cell growth;recombinant E. coli;resistance;results;study;sustainable;vanillin;well-known polyhydroxyalkanoate
10.1002/(SICI)1097-0290(20000605)68:5<524::AID-BIT6>3.0.CO;2-T;10.1002/yea.3067;10.1007/BF00500854;10.1007/s00253-005-0142-3;10.1007/s00449-017-1743-9;10.1007/s10295-003-0049-x;10.1007/s10295-004-0136-7;10.1007/s10295-015-1718-2;10.1007/s10529-010-0513-4;10.1016/j.biortech.2008.03.071;10.1016/j.biortech.2009.11.046;10.1016/j.biortech.2017.02.061;10.1016/j.biortech.2017.05.197;10.1016/j.biortech.2018.09.122;10.1016/j.jclepro.2017.05.209;10.1016/j.nbt.2013.10.004;10.1016/j.watres.2009.12.031;10.1016/S0079-6700(00)00035-6;10.1016/S0167-7799(98)01194-9;10.1016/S0960-8524(01)00212-7;10.1016/S0960-8524(99)00161-3;10.1016/S1001-0742(09)60295-3;10.1021/acs.biomac.7b01446;10.1021/bm4010244;10.1021/ie801542g;10.1038/nbt0208-169;10.1073/pnas.1217958110;10.1111/1462-2920.12636;10.1111/j.1365-2672.2012.05391.x;10.1126/science.1114736;10.1128/AEM.05008-11;10.1128/JB.183.1.301-308.2001;10.1146/annurev.arplant.043008.092125;10.1186/1475-2859-8-47;10.1186/1754-6834-2-26;10.1186/1756-0500-6-219;10.2174/2212796811206010014;10.2514/6.2013-2933;10.3389/fbioe.2015.00017;10.3389/fmicb.2014.00247;10.3389/fpls.2013.00107;10.4014/jmb.1705.05020;[10.1002/(SICI)1097-0290(1999)66:4<203::AID-BIT1>3.0.CO;2-#, 10.1002/(SICI)1097-0290(1999)66:4&lt;203::AID-BIT1&gt;3.0.CO;2-#]
Konkuk Univ
Bhatia, S K;Choi, T R;Gurav, R;Jung, H R;Ko, B J;Lee, J H;Moon, Y M;Park, J Y;Park, Y L;Song, H S;Yang, S Y;Yang, Y H
Jung, H R: Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea
Bhatia, Shashi;Gurav, Ranjit G;Ko, Byoung;Park, Jun;Song, Hun-Suk
2017M3A9E4077234;NRF-2015M1A5A1037196;NRF2016R1D1A1B03932301;PE18900
48
null
South Korea
Konkuk Univ;Osong Med Innovat Fdn
Jung, Hye-Rim
Bronze
3-HYDROXYVALERATE;BACTERIA;BIOMASS HYDROLYSATE;FERMENTATION;GROWTH;INHIBITORS;MECHANISMS;OVEREXPRESSION;POLY-3-HYDROXYBUTYRATE;POLYHYDROXYALKANOATES
Jung, Hye-Rim; Lee, Ju-Hee; Moon, Yu-Mi; Choi, Tae-Rim; Yang, Soo-Yeon; Song, Hun-Suk; Park, Jun Young; Park, Ye Lim; Bhatia, Shashi Kant; Gurav, Ranjit; Ko, Byoung Joon; Yang, Yung-Hun;
null
Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea;Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea;Osong Med Innovat Fdn, New Drug Dev Ctr, Cheongju 28160, South Korea
Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea;Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea;Osong Med Innovat Fdn, New Drug Dev Ctr, Cheongju 28160, South Korea
1738-8872
Escherichia coli;furfural;lignocellulosic hydrolysates;Polyhydroxybutyrate;resistance
5
1978;1997;1998;1999;2000;2001;2002;2003;2004;2006;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
27
Konkuk Univ, Coll Engn, Dept Biol Engn, Seoul 05029, South Korea;Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea
J. Microbiol. Biotechnol.
Yang, Yung-Hun
KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY
(bktB;(PHB);,;4-hydroxybenzaldehyde;a;absence;addition;an;and;application;as;be;bio-based;biodegradable;by;cell;coli;compound;confer;cost-effective;could;during;E.;especially;eutropha;feasibility;fermentative;findings;for;found;from;furfural;generation;genes;glucose;good;growth;H16);has;however;hydrolysate;hydrolysates;improved;in;increased;indicate;inhibitors;innovative;introduction;investigated;is;its;lignocellulose;limited;most;non-edible;observed;of;opposed;our;petroleum-based;phaB;phaC;PHB;plastics;polyhydroxyalkanoate;polyhydroxybutyrate;polymer;potential;presence;pretreatment;processes;product;production;promising;Ralstonia;recombinant;replace;resistance;resource;results;show;stimulate;strategy;study;substrate;such;suggesting;sustainable;synthetic;target;that;the;these;this;to;used;using;vanillin;was;we;well-known
Konkuk Univ
Polyhydroxybutyrate (PHB), the most well-known polyhydroxyalkanoate, is a bio-based, biodegradable polymer that has the potential to replace petroleum-based plastics. Lignocellulose hydrolysate, a non-edible resource, is a promising substrate for the sustainable, fermentative production of PHB. However, its application is limited by the generation of inhibitors during the pretreatment processes. In this study, we investigated the feasibility of PHB production in E. coli in the presence of inhibitors found in lignocellulose hydrolysates. Our results show that the introduction of PHB synthetic genes (bktB, phaB, and phaC from Ralstonia eutropha H16) improved cell growth in the presence of the inhibitors such as furfural, 4-hydroxybenzaldehyde, and vanillin, suggesting that PHB synthetic genes confer resistance to these inhibitors. In addition, increased PHB production was observed in the presence of furfural as opposed to the absence of furfural, suggesting that this compound could be used to stimulate PHB production. Our findings indicate that PHB production using lignocellulose hydrolysates in recombinant E. coli could be an innovative strategy for cost-effective PHB production, and PHB could be a good target product from lignocellulose hydrolysates, especially glucose.
AAE-9014-2020;ABA-1336-2021;ABG-2763-2020;HPH-3570-2023;N-4550-2018
3-HYDROXYVALERATE;BACTERIA;BIOMASS HYDROLYSATE;FERMENTATION;GROWTH;INHIBITOR;MECHANISM;OVEREXPRESSION;POLY(3-HYDROXYBUTYRATE);POLYHYDROXYALKANOATES
2
null
Escherichia coli;furfural;lignocellulose hydrolysate;Polyhydroxybutyrate;resistance
9
ESCHERICHIA-COLI;3-HYDROXYVALERATE;BACTERIA;BIOMASS HYDROLYSATE;FERMENTATION;furfural;GROWTH;INHIBITOR;LIGNOCELLULOSIC HYDROLYSATE;MECHANISM;Overexpression;Poly(3-hydroxybutyrate);POLYHYDROXYALKANOATES;Polyhydroxybutyrate;resistance
WOS:000469201000012
Konkuk Univ, Seoul, South Korea;Osong Med Innovat Fdn, Cheongju, South Korea
South Korea
2,019
null
0000-0001-9841-4022;0000-0002-7688-6069;0000-0002-8091-2952
null
null
English
null
ANNU REV PLANT BIOL;APPL ENVIRON MICROB;APPL MICROBIOL BIOT;BIOMACROMOLECULES;BIOPROC BIOSYST ENG;BIORESOURCE TECHNOL;BIOTECHNOL BIOENG;BIOTECHNOL BIOFUELS;BIOTECHNOL LETT;BMC Res Notes;Br J Hosp Med;CURRENT CHEM BIOL;ENVIRON ENG RES;ENVIRON MICROBIOL;EUR J APPL MICROBIOL;FEBS LETT;FRONT BIOENG BIOTECH;FRONT MICROBIOL;FRONT PLANT SCI;IND ENG CHEM RES;J APPL MICROBIOL;J BACTERIOL;J CLEAN PROD;J ENVIRON SCI;J IND MICROBIOL BIOT;J MICROBIOL BIOTECHN;MICROB CELL FACT;MICROBIOL;NAT BIOTECHNOL;NEW BIOTECHNOL;P NATL ACAD SCI USA;Production of Bio-ethylene;PROG POLYM SCI;SCIENCE;TRENDS BIOTECHNOL;Waste and Biomass Valorization;WATER RES;YEAST
Bhatia, Shashi Kant;Choi, Tae-Rim;Gurav, Ranjit;Jung, Hye-Rim;Ko, Byoung Joon;Lee, Ju-Hee;Moon, Yu-Mi;Park, Jun Young;Park, Ye Lim;Song, Hun-Suk;Yang, Soo-Yeon;Yang, Yung-Hun
2024-03-11 ER
[Anonymous];Ahn, J;Barciszewski, J;Bhatia, S K;Braunegg, G;Brodin, M;Broeren M.;Carroll, A;Cesário, M T;Dietrich Diane;Dietrich, K;Du C.;Gorsich, S W;Han, M J;Jeon, J M;Johnson, K;Kumar, P;Lynd, L R;Madkour, M H;Mezzina, M P;Mills, T Y;Moon, J;Nieves, L M;Palmqvist, E;Phylactides, M;Ragauskas, A J;Saha, B C;Seo, H M;Sharma H.K.;Silva, L F;Sims, R E H;Song, H S;Steinbüchel, A;Sudesh, K;Sun, Y;Van Der Weijde, T;Wang, Q;Wang, W;Wang, X;Wen, Q X;Yang, Y H;Yu, J;Zaldivar, J
HZ9TT
Seoul, South Korea;Seoul, South Korea.
28
null
2
null
31,030,455
Bhatia, Shashi Kant;Choi, Tae-Rim;Gurav, Ranjit;Jung, Hye-Rim;Ko, Byoung Joon;Lee, Ju-Hee;Moon, Yu-Mi;Park, Jun Young;Park, Ye Lim;Song, Hun-Suk;Yang, Soo-Yeon;Yang, Yung-Hun
J MICROBIOL BIOTECHN
Cheongju, South Korea;Seoul, South Korea
Bernauer, H S;Hoffmann, M;Pogorevc, D;Popoff, A;Steinmetz, H;Tang, Y;Wenzel, S C;Zipf, G
10.1021/acssynbio.9b00023
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
2453321h6y461hn5p5442l142n5a3s5i3i695q
Biosynthesis and Heterologous Production of Argyrins
Univ Saarland
null
Pogorevc, D (corresponding author), Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany.;Pogorevc, D (corresponding author), Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany.
null
Bernauer, Hubert S;Hoffmann, Michael;Pogorevc, Domen;Popoff, Alexander;Steinmetz, Heinrich;Tang, Ying;Wenzel, Silke C;Zipf, Gregor
Biochemical Research Methods
German Federal Ministry of Education and Research [FKZ: 031A155]
WOS
Pogorevc, D
ATG Biosynthet GmbH, Merzhausen, Germany;BASF SE, Ludwigshafen, Germany;Helmholtz Ctr Infect Res HZI, Braunschweig, Germany;Hunan Inst Microbiol, Hunan, Peoples R China;Hunan Normal Univ, Hunan, Peoples R China;Saarland Univ, Saarbrucken, Germany
8
and;Argyrins;biosynthesis;Heterologous;of;production
2
Popoff, Alexander;Scherzer (Pogorevc), Domen;Tang, Ying
AMER CHEMICAL SOC
ATG Biosynthet GmbH, D-79249 Merzhausen, Germany;BASF SE, D-67056 Ludwigshafen, Germany;Helmholtz Ctr Infect Res HZI, Microbial Strain Collect, D-38124 Braunschweig, Germany;Hunan Inst Microbiol, Changsha 410009, Hunan, Peoples R China;Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Hunan Prov Key Lab Microbial Mol Biol, Changsha 410081, Hunan, Peoples R China;Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany;Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany.; Pogorevc, D (corresponding author), Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany;Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany
Article
Univ Saarland
WASHINGTON
null
null
ATG Biosynthet GmbH;BASF SE;Helmholtz Ctr Infect Res HZI;Hunan Inst Microbiol;Hunan Normal Univ;Saarland Univ
German Federal Ministry of Education and Research
Pogorevc, D (corresponding author), Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany.; Pogorevc, D (corresponding author), Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany.
1133
Bernauer, Hubert S;Hoffmann, Michael;Pogorevc, Domen;Popoff, Alexander;Steinmetz, Heinrich;Tang, Ying;Wenzel, Silke C;Zipf, Gregor
39
7
468,697,000,022
German Federal Ministry of Education and Research [FKZ: 031A155]
China;Germany
ACS SYNTHETIC BIOLOGY
Germany
null
null
Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany
2161-5063
Bernauer, H S;Hoffmann, M;Pogorevc, D;Popoff, A;Steinmetz, H;Tang, Y;Wenzel, S C;Zipf, G
MAY
domen.pogorevc@helmholtz-hips.de
Argyrins;biosynthesis;Heterologous Production
8
J
Biochemistry & Molecular Biology
160 mg/L;ADENYLATION DOMAIN;antibiotics;antitumorigenic;argyrin;Argyrins;around 20-fold higher yields;BACTERIAL PROTEIN-SYNTHESIS;biosynthesis;chromosomal deletion;COMBINATORIAL BIOSYNTHESIS;cyclic octapeptides;different approaches;F3;FAMILY;future supply;G3;gene synthesis fragments;GENE-CLUSTER;heterologous argyrin production;heterologous expression;heterologous expression system;Heterologous Production;heterologous production platform;host strain Myxococcus xanthus DK1622;IDENTIFICATION;immunosuppressant activities;IMMUNOSUPPRESSIVE CYCLIC-PEPTIDES;J;K;L);led;myxobacteria;myxobacterial producer strain Cystobacter sp;native biosynthetic gene cluster (BGC) sequence;native producer;NATURAL-PRODUCTS;non-ribosomal peptide synthetase pathway;nonribosomal peptide synthetase;novel derivatives;NUCLEOTIDE-SEQUENCE;production system;promising antimicrobial;SBCb004;several novel argyrin derivatives (A2;study;Synthetic gene cluster;template synthetic BGC versions;versatile platform;well-expressed lipopeptide pathway
Pogorevc, D
ADENYLATION DOMAIN;ANTIBIOTICS;argyrin;BACTERIAL PROTEIN-SYNTHESIS;COMBINATORIAL BIOSYNTHESIS;GENE-CLUSTER;heterologous expression;IMMUNOSUPPRESSIVE CYCLIC-PEPTIDES;myxobacteria;NATURAL-PRODUCTS;nonribosomal peptide synthetase;NUCLEOTIDE-SEQUENCE;Synthetic gene cluster
1121
[Pogorevc, Domen; Tang, Ying; Hoffmann, Michael; Popoff, Alexander; Wenzel, Silke C.] Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany. [Pogorevc, Domen; Tang, Ying; Hoffmann, Michael; Popoff, Alexander; Wenzel, Silke C.] Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany. [Tang, Ying] Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Hunan Prov Key Lab Microbial Mol Biol, Changsha 410081, Hunan, Peoples R China. [Zipf, Gregor; Bernauer, Hubert S.] ATG Biosynthet GmbH, D-79249 Merzhausen, Germany. [Steinmetz, Heinrich] Helmholtz Ctr Infect Res HZI, Microbial Strain Collect, D-38124 Braunschweig, Germany. [Tang, Ying] Hunan Inst Microbiol, Changsha 410009, Hunan, Peoples R China. [Hoffmann, Michael] BASF SE, D-67056 Ludwigshafen, Germany.
We would like to thank Dr. Ronald Garcia for provision and advice on the argyrin producer Cystobacter sp. SBCb004, Irene Kochems and Douglas Gatte Pichi for their efforts in SBCb004 engineering, Sara Andes and Jack Stanley for assistance in arg BGC cloning, Dr. Nestor Zaburannyi for bioinformatics support, and Eva Luxemburger, Daniel Sauer, and Dr. Kirsten Harmrolfs for HPLC MS and NMR measurements. Furthermore, we gratefully acknowledge Prof. Dr. Rolf Muller for constantly supporting and discussing this study. This work was generously funded by a grant from the German Federal Ministry of Education and Research (FKZ: 031A155).
160 mg/L;antitumorigenic;argyrins;around 20-fold higher yields;chromosomal deletion;cyclic octapeptides;different approaches;F3;family;future supply;G3;gene synthesis fragments;heterologous argyrin production;heterologous expression system;heterologous production platform;host strain Myxococcus xanthus DK1622;identification;immunosuppressant activities;J;K;L);led;myxobacterial producer strain Cystobacter sp;native biosynthetic gene cluster (BGC) sequence;native producer;non-ribosomal peptide synthetase pathway;novel derivatives;production system;promising antimicrobial;SBCb004;several novel argyrin derivatives (A2;study;template synthetic BGC versions;versatile platform;well-expressed lipopeptide pathway
10.1002/anie.200503737;10.1002/anie.200900406;10.1002/anie.201000140;10.1002/anie.201208344;10.1002/anie.201409964;10.1002/anie.201508277;10.1002/anie.201609079;10.1002/anie.201802479;10.1002/bit.10202;10.1002/bit.25560;10.1002/cbic.201200479;10.1002/cmdc.201000080;10.1007/0-387-30747-8_3;10.1007/BF01030015;10.1007/s00726-014-1846-4;10.1007/s10295-015-1723-5;10.1007/s10529-012-0913-8;10.1007/s12282-016-0717-0;10.1016/0022-2836(69)90288-5;10.1016/0378-1119(82)90023-3;10.1016/j.aca.2008.06.036;10.1016/j.canlet.2017.04.003;10.1016/j.ccr.2008.05.016;10.1016/j.cell.2015.11.031;10.1016/j.chembiol.2005.12.012;10.1016/j.chembiol.2010.01.016;10.1016/j.chembiol.2012.01.007;10.1016/j.chembiol.2015.04.015;10.1016/j.jbiotec.2014.07.447;10.1016/j.ymben.2017.10.004;10.1016/S0022-2836(05)80360-2;10.1016/S0076-6879(09)04803-4;10.1016/S0076-6879(09)04808-3;10.1016/S1074-5521(00)00011-9;10.1016/S1074-5521(00)00118-6;10.1016/S1074-5521(00)80014-9;10.1016/S1074-5521(99)80082-9;10.1016/S1367-5931(00)00235-0;10.1021/acs.jnatprod.5b01055;10.1021/ol017184m;10.1021/sb300080t;10.1038/nature14100;10.1038/nm.3704;10.1039/c001260m;10.1039/c2np20085f;10.1039/c2sc21722h;10.1039/c3sc53163e;10.1039/c4np00007b;10.1039/c4np00011k;10.1039/c4ob02107j;10.1039/c5np00099h;10.1039/c6np00106h;10.1039/c8sc02046a;10.1073/pnas.0608589103;10.1093/nar/16.1.355;10.1093/nar/16.1.356;10.1093/nar/gkn499;10.1093/nar/gkv437;10.1101/PDB.PROT4022;10.1111/j.1365-2958.1995.tb02262.x;10.1126/science.7604280;10.1128/AAC.03326-14;10.1128/AAC.46.9.2772-2778.2002;10.1128/AAC.47.9.2823-2830.2003;10.1128/AEM.01503-06;10.1128/AEM.02841-09;10.1128/JB.181.13.4050-4061.1999;10.1146/annurev.micro.58.030603.123615;10.1186/1471-2148-7-78;10.1186/1471-2180-11-199;10.1371/journal.pone.0042657;10.3109/07853890.2011.579151;10.3390/microorganisms6030084;10.7164/antibiotics.49.145;10.7164/antibiotics.49.150;10.7164/antibiotics.55.543;10.7164/antibiotics.55.715;[10.1038/ja.2012.54, 10.1038/ja.2012.27];[10.1128/AAC.02400-16, 10.1128/aac.02400-16]
Saarland Univ
Bernauer, H S;Hoffmann, M;Pogorevc, D;Popoff, A;Steinmetz, H;Tang, Y;Wenzel, S C;Zipf, G
Pogorevc, D: Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany
null
FKZ: 031A155
84
null
Germany
ATG Biosynthet GmbH;BASF SE;Helmholtz Ctr Infect Res HZI;Hunan Inst Microbiol;Hunan Normal Univ;Saarland Univ
Pogorevc, Domen
null
ADENYLATION DOMAIN;ANTIBIOTICS;BACTERIAL PROTEIN-SYNTHESIS;COMBINATORIAL BIOSYNTHESIS;GENE-CLUSTER;IMMUNOSUPPRESSIVE CYCLIC-PEPTIDES;MYXOBACTERIA;NATURAL-PRODUCTS;NONRIBOSOMAL PEPTIDE SYNTHETASE;NUCLEOTIDE-SEQUENCE
Pogorevc, Domen; Tang, Ying; Hoffmann, Michael; Zipf, Gregor; Bernauer, Hubert S.; Popoff, Alexander; Steinmetz, Heinrich; Wenzel, Silke C.;
null
ATG Biosynthet GmbH, D-79249 Merzhausen, Germany;BASF SE, D-67056 Ludwigshafen, Germany;Helmholtz Ctr Infect Res HZI, Microbial Strain Collect, D-38124 Braunschweig, Germany;Hunan Inst Microbiol, Changsha 410009, Hunan, Peoples R China;Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Hunan Prov Key Lab Microbial Mol Biol, Changsha 410081, Hunan, Peoples R China;Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany;Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany
ATG Biosynthet GmbH, D-79249 Merzhausen, Germany;BASF SE, D-67056 Ludwigshafen, Germany;Helmholtz Ctr Infect Res HZI, Microbial Strain Collect, D-38124 Braunschweig, Germany;Hunan Inst Microbiol, Changsha 410009, Hunan, Peoples R China;Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Hunan Prov Key Lab Microbial Mol Biol, Changsha 410081, Hunan, Peoples R China;Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany;Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany
null
argyrin;heterologous expression;myxobacteria;nonribosomal peptide synthetase;Synthetic gene cluster
5
1969;1982;1988;1990;1995;1996;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
21
Saarland Univ, Dept Microbial Nat Prod, Helmholtz Inst Pharmaceut Res Saarland HIPS, Helmholtz Ctr Infect Res HZI, D-66123 Saarbrucken, Germany;Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany
ACS Synth. Biol.
Wenzel, Silke C
AMER CHEMICAL SOC
(A2;(BGC);,;160;20-fold;a;activities;after;also;and;antimicrobial;antitumorigenic;applied;approaches;argyrin;argyrins;around;as;assembled;BGC;biosynthetic;characterized;chromosomal;cluster;compared;cyclic;Cystobacter;deletion;derivatives;derive;designed;different;DK1622;engineer;established;exhibiting;expression;F3;family;finally;for;fragments;from;future;G3;gene;heterologous;higher;host;I;identification;identified;immunosuppressant;improve;in;increased;J;K;L);led;lipopeptide;mg/L;myxobacterial;Myxococcus;native;non-ribosomal;novel;octapeptides;of;optimized;pathway;peptide;platform;producer;production;promising;provides;represent;SBCb004;sequence;several;sp;strain;study;supply;synthesis;synthetase;synthetic;system;template;the;thereof;they;this;to;using;versatile;versions;was;well-expressed;were;which;xanthus;yields
Saarland Univ
Argyrins represent a family of cyclic octapeptides exhibiting promising antimicrobial, antitumorigenic and immunosuppressant activities. They derive from a non-ribosomal peptide synthetase pathway, which was identified and characterized in this study from the myxobacterial producer strain Cystobacter sp. SBCb004. Using the native biosynthetic gene cluster (BGC) sequence as template synthetic BGC versions were designed and assembled from gene synthesis fragments. A heterologous expression system was established after chromosomal deletion of a well-expressed lipopeptide pathway from the host strain Myxococcus xanthus DK1622. Different approaches were applied to engineer and improve heterologous argyrin production, which was finally increased to 160 mg/L, around 20-fold higher yields compared to the native producer. Heterologous production platform also led to identification of several novel argyrin derivatives (A2, F3, G3, I, J, K, and L). The optimized production system provides a versatile platform for future supply of argyrins and novel derivatives thereof.
null
ADENYLATION DOMAIN;ANTIBIOTICS;BACTERIAL PROTEIN-SYNTHESIS;COMBINATORIAL BIOSYNTHESIS;GENE-CLUSTER;IMMUNOSUPPRESSIVE CYCLIC-PEPTIDES;MYXOBACTERIA;NATURAL-PRODUCTS;NONRIBOSOMAL PEPTIDE SYNTHETASE;NUCLEOTIDE-SEQUENCE
3
null
argyrin;heterologous expression;myxobacteria;nonribosomal peptide synthetase;Synthetic gene cluster
25
adenylation domains;ANTIBIOTICS;argyrin;BACTERIAL PROTEIN-SYNTHESIS;COMBINATORIAL BIOSYNTHESIS;GENE-CLUSTER;heterologous expression;IMMUNOSUPPRESSIVE CYCLIC-PEPTIDES;myxobacteria;NATURAL-PRODUCTS;nonribosomal peptide synthetase;NUCLEOTIDE-SEQUENCE;Synthetic gene cluster
WOS:000468697000022
ATG Biosynthet GmbH, Merzhausen, Germany;BASF SE, Ludwigshafen, Germany;Helmholtz Ctr Infect Res HZI, Braunschweig, Germany;Hunan Inst Microbiol, Hunan, Peoples R China;Hunan Normal Univ, Hunan, Peoples R China;Saarland Univ, Saarbrucken, Germany
China;Germany
2,019
null
0000-0001-5582-059X;0000-0001-8495-1572;0000-0003-0378-9150
null
null
English
null
2017 IND BIOTECHNOLO;ACS SYNTH BIOL;AMINO ACIDS;ANAL CHIM ACTA;ANGEW CHEM INT EDIT;ANN MED;ANNU REV MICROBIOL;ANTIMICROB AGENTS CH;APPL ENVIRON MICROB;BIOSYNTHESIS H UNPUB;BIOTECHNOL BIOENG;BIOTECHNOL LETT;BMC EVOL BIOL;BMC MICROBIOL;BREAST CANCER-TOKYO;CANC RES;CANCER CELL;CANCER LETT;CELL;CHEM BIOL;CHEM SCI;CHEMBIOCHEM;CHEMMEDCHEM;CURR OPIN CHEM BIOL;GENE;J ANTIBIOT;J BACTERIOL;J BIOTECHNOL;J IND MICROBIOL BIOT;J MOL BIOL;J NAT PROD;METAB ENG;METHOD ENZYMOL;MICROORGANISMS;MOL CLONING LAB MANU;MOL MICROBIOL;NAT MED;NAT PROD REP;NATURE;NUCLEIC ACIDS RES;ORG BIOMOL CHEM;ORG LETT;P NATL ACAD SCI USA;PLOS ONE;SCIENCE;The Prokaryotes
Bernauer, Hubert S;Hoffmann, Michael;Pogorevc, Domen;Popoff, Alexander;Steinmetz, Heinrich;Tang, Ying;Wenzel, Silke C;Zipf, Gregor
2024-03-11 ER
[Anonymous];Altschul, S F;Alvarez, R H;Arnison, P G;Bachmann, B O;Baumann, S;Beasley, F C;Beck, E;Berod, L;Bian, X Y;Bielecki, P;Boyer, H W;Bérdy, J;Bülow, L;Chai, Y;Chen, C H;Chen, X;Crüsemann, M;Doekel, S;Du, L C;Ferrari, P;Finking, R;Finn Il D.;Fu, J;Garcia, R O;Gaudelli, N M;Gemperlein, K;Han, J W;Held, J;Herrmann, J;Jones, A K;Julien, B;Kashefi, K;Katz, L;Kries, H;Krug, D;Kudo, F;Lau, J;Ley, S V;Li, J;Magrini, V;Miao, V;Mohr, K I;Newman, D J;Nguyen, K T;Nickeleit, I;Nyfeler, B;Osswald, C;Perlova, O;Rausch, C;Reichenbach;Rose, R E;Sambrook J.;Sasse, F;Schäberle, T F;Selva, E;Shen, B;Shimkets L.J.;Siodlak, D;Stachelhaus, T;Stauch, B;Stevens, D C;Sucipto, H;Süssmuth, R D;Thomas, M G;Tokarski, Z;Ullrich, A;Vollbrecht, L;Von Döhren, H;Walsh, C T;Weber, T;Weissman, K J;Wenzel, S C;Winn, M;Yan, F
HZ2RT
Saarbrucken, Germany;Saarbrucken, Germany.
26
null
6
null
30,995,838
Bernauer, Hubert S;Hoffmann, Michael;Pogorevc, Domen;Popoff, Alexander;Steinmetz, Heinrich;Tang, Ying;Wenzel, Silke C;Zipf, Gregor
ACS SYNTH BIOL
Braunschweig, Germany;Hunan, Peoples R China;Ludwigshafen, Germany;Merzhausen, Germany;Saarbrucken, Germany
Castro, S;Danino, T;Harimoto, T;Hinchliffe, T E;Mather, W;Singer, Z S;Velazquez, O S;Zhang, J
10.1073/pnas.1820824116
null
2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
3x24j85sh1n30573y306l3a366a545g37634m
Rapid screening of engineered microbial therapies in a 3D multicellular model
Columbia Univ
null
Danino, T (corresponding author), Columbia Univ, Data Sci Inst, New York, NY 10027 USA.;Danino, T (corresponding author), Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.;Danino, T (corresponding author), Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA.
null
Castro, Samuel;Danino, Tal;Harimoto, Tetsuhiro;Hinchliffe, Taylor E;Mather, William;Singer, Zakary S;Velazquez, Oscar S;Zhang, Joanna
Multidisciplinary Sciences
Honjo International Foundation Scholarship; NIH Ruth L. Kirschstein National Research Service Award; NIH [R00CA197649-02]; Department of Defense (DoD) Idea Development Award [LC160314]; DoD Era of Hope Scholar Award [BC160541]; NIH/National Cancer Institute Cancer Center [P30CA013696]; CDMRP [LC160314, 917541] Funding Source: Federal RePORTER
WOS
Danino, T
Columbia Univ, New York, NY USA;Univ Calif San Diego, La Jolla, CA USA
116
3D;a;engineered;in;microbial;model;multicellular;of;rapid;screening;therapies
1
Harimoto, Tetsuhiro;Zhang, Joanna
NATL ACAD SCIENCES
Columbia Univ, Data Sci Inst, New York, NY 10027 USA;Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA;Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.; Danino, T (corresponding author), Columbia Univ, Data Sci Inst, New York, NY 10027 USA.; Danino, T (corresponding author), Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA;Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA;Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA
Article
Columbia Univ
WASHINGTON
null
null
Columbia Univ;Univ Calif San Diego
CDMRP;Department of Defense (DoD) Idea Development Award;DoD Era of Hope Scholar Award;Honjo International Foundation Scholarship;NIH;NIH Ruth L. Kirschstein National Research Service Award;NIH/National Cancer Institute Cancer Center
Danino, T (corresponding author), Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.; Danino, T (corresponding author), Columbia Univ, Data Sci Inst, New York, NY 10027 USA.; Danino, T (corresponding author), Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA.
9007
Castro, Samuel;Danino, Tal;Harimoto, Tetsuhiro;Hinchliffe, Taylor E;Mather, William;Singer, Zakary S;Velazquez, Oscar S;Zhang, Joanna
30
4
466,446,500,054
CDMRP [LC160314, 917541] Funding Source: Federal RePORTER;Department of Defense (DoD) Idea Development Award [LC160314];DoD Era of Hope Scholar Award [BC160541];Honjo International Foundation Scholarship;NIH [R00CA197649-02];NIH Ruth L. Kirschstein National Research Service Award;NIH/National Cancer Institute Cancer Center [P30CA013696]
USA
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
USA;USA.;
null
null
Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA
0027-8424
Castro, S;Danino, T;Harimoto, T;Hinchliffe, T E;Mather, W;Singer, Z S;Velazquez, O S;Zhang, J
APR 30
td2506@columbia.edu
3D multicellular model;microbial therapies;rapid screening
8
J
Science & Technology - Other Topics
3D multicellular model;ability;animal-based testing regimes;antitumor therapeutic molecules via several synthetic gene circuits;BACTERIA;bacteria-in-spheroid coculture (BSCC) platform;bacterial dynamics;bacterial therapy;biocontainment;broad applicability;CANCER;cancer therapy;candidates;cells;challenge;clinical applications;clinical translation;critical therapeutic parameters;disease progression;disease sites;diseases;DRUG;efficacies;efficacy;engineer new therapies;engineering living cells;Escherichia coli;high similarity;high-throughput framework;high-throughput screening;host cell types;host-microbe interactions;infections;inflammation;INVASION;library;Listeria monocytogenes;major bottleneck;metabolic disorders;microbes;microbial therapies;multicellular spheroids;outpaces;platform;profile diverse microbial species;Proteus mirabilis;quantitative comparison;rapid screening;Salmonella typhimurium strains;SALMONELLA-TYPHIMURIUM;scalability;sense;serve;significant tumor reduction;syngeneic mouse model;synthetic biology;synthetic gene circuits;tests host species;therapeutic paradigms;therapeutic payloads;throughput;timescale;vitro approaches;weeks
Harimoto, T
BACTERIA;bacterial therapy;CANCER;cancer therapy;CELLS;DRUG;high-throughput screening;INVASION;SALMONELLA-TYPHIMURIUM;Synthetic biology
9002
[Harimoto, Tetsuhiro; Singer, Zakary S.; Velazquez, Oscar S.; Zhang, Joanna; Castro, Samuel; Hinchliffe, Taylor E.; Danino, Tal] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. [Mather, William] Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA. [Danino, Tal] Columbia Univ, Data Sci Inst, New York, NY 10027 USA. [Danino, Tal] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA.
We thank N. Arpaia, M. Omar Din, and J. Hasty for their helpful comments and suggestions. We thank the Herbert Irving Comprehensive Cancer Center Molecular Pathology Shared Resources Facility for help with histological sample processing. This work was supported in part by the Honjo International Foundation Scholarship (T.H.), NIH Ruth L. Kirschstein National Research Service Award (Z.S.S.), NIH Pathway to Independence Award (R00CA197649-02), Department of Defense (DoD) Idea Development Award LC160314, DoD Era of Hope Scholar Award BC160541, and NIH/National Cancer Institute Cancer Center Support Grant P30CA013696.
ability;animal-based testing regimes;antitumor therapeutic molecules via several synthetic gene circuits;bacteria;bacteria-in-spheroid coculture (BSCC) platform;bacterial dynamics;biocontainment;broad applicability;cancer;candidates;challenge;clinical applications;clinical translation;critical therapeutic parameters;disease progression;disease sites;diseases;efficacies;efficacy;engineer new therapies;engineering living cells;Escherichia coli;high similarity;high-throughput framework;host cell types;host-microbe interactions;infections;inflammation;library;Listeria monocytogenes;major bottleneck;metabolic disorders;microbes;multicellular spheroids;outpaces;platform;profile diverse microbial species;Proteus mirabilis;quantitative comparison;Salmonella typhimurium strains;scalability;sense;serve;significant tumor reduction;syngeneic mouse model;synthetic biology;synthetic gene circuits;tests host species;therapeutic paradigms;therapeutic payloads;throughput;timescale;vitro approaches;weeks
10.1002/bit.20883;10.1002/bit.25184;10.1016/0264-410X(95)00173-X;10.1016/j.cell.2016.05.082;10.1016/j.cell.2018.05.039;10.1016/j.coisb.2017.05.009;10.1016/j.copbio.2017.06.004;10.1016/j.jamcollsurg.2007.06.283;10.1016/j.jmb.2005.10.076;10.1038/291238a0;10.1038/gt.2008.188;10.1038/nature18930;10.1038/nbt.2284;10.1038/nbt.2989;10.1038/nbt.3805;10.1038/nbt.3879;10.1038/nbt.4222;10.1038/ncomms15028;10.1038/nmicrobiol.2017.83;10.1038/nprot.2008.226;10.1038/nrc2934;10.1038/nrmicro.2017.172;10.1038/s41467-018-03233-9;10.1038/s41589-018-0056-x;10.1038/srep15681;10.1053/j.gastro.2014.09.042;10.1073/pnas.0507681102;10.1073/pnas.1414558112;10.1073/pnas.1522193112;10.1073/pnas.222539699;10.1073/pnas.251543698;10.1098/rsif.2014.0065;10.1126/science.aac7341;10.1126/science.aan4236;10.1126/scitranslmed.aaa3519;10.1126/scitranslmed.aak9537;10.1126/scitranslmed.aao2586;10.1158/0008-5472.CAN-07-2984;10.1177/1087057117696795;10.1186/s12934-015-0383-5;10.1200/JCO.2002.20.1.142;10.12659/MSM.901880;10.1371/journal.pone.0188960;10.15252/msb.20167416;10.1538/expanim.16-0033;10.18632/oncotarget.9935;10.2174/156652310790945539;10.3390/toxins7051702;10.3791/2693
Columbia Univ
Castro, S;Danino, T;Harimoto, T;Hinchliffe, T E;Mather, W;Singer, Z S;Velazquez, O S;Zhang, J
Harimoto, T: Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA
null
917541;BC160541;LC160314;P30CA013696;R00CA197649-02
50
null
USA
Columbia Univ;Univ Calif San Diego
Harimoto, Tetsuhiro
Bronze, Green Submitted, Green Published
BACTERIA;CANCER;CELLS;DRUG;INVASION;SALMONELLA-TYPHIMURIUM
Harimoto, Tetsuhiro; Singer, Zakary S.; Velazquez, Oscar S.; Zhang, Joanna; Castro, Samuel; Hinchliffe, Taylor E.; Mather, William; Danino, Tal;
null
Columbia Univ, Data Sci Inst, New York, NY 10027 USA;Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA;Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA;Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA
Columbia Univ, Data Sci Inst, New York, NY 10027 USA;Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA;Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA;Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA
null
bacterial therapy;cancer therapy;high-throughput screening;Synthetic biology
18
1981;1994;1996;2001;2002;2006;2007;2008;2009;2010;2011;2012;2014;2015;2016;2017;2018
22
Columbia Univ, Data Sci Inst, New York, NY 10027 USA;Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA;Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10027 USA
Proc. Natl. Acad. Sci. U. S. A.
Danino, Tal
NATL ACAD SCIENCES
(BSCC);,;a;ability;accelerate;address;and;animal-based;antitumor;applicability;applications;approaches;as;bacteria;bacteria-in-spheroid;bacterial;be;been;biocontainment;biology;bottleneck;broad;by;can;cancer;candidates;cell;cells;challenge;circuits;clinical;coculture;coli;comparison;creating;critical;delivering;demonstrate;disease;diseases;disorders;diverse;dynamically;dynamics;efficacies;efficacy;enables;engineer;engineered;engineering;Escherichia;exhibiting;expanded;expressing;far;for;framework;gene;have;here;high;high-throughput;host;host-microbe;however;identify;in;including;infections;inflammation;intelligently;interactions;is;last;library;limited;Listeria;living;long-term;major;may;metabolic;microbes;microbial;mirabilis;model;molecules;monitoring;monocytogenes;mouse;multicellular;new;of;our;outpaces;over;paradigms;parameters;payloads;platform;present;profile;progression;Proteus;quantitative;rapidly;reduction;regimes;respond;Salmonella;scalability;screen;sense;serve;several;show;significant;similarity;simultaneously;sites;species;specifically;spheroids;strains;such;syngeneic;synthetic;testing;tests;that;the;their;therapeutic;therapies;this;throughput;timescale;to;transforming;translation;tumor;types;typhimurium;understanding;using;various;via;vitro;we;weeks;within
Columbia Univ
Synthetic biology is transforming therapeutic paradigms by engineering living cells and microbes to intelligently sense and respond to diseases including inflammation, infections, metabolic disorders, and cancer. However, the ability to rapidly engineer new therapies far outpaces the throughput of animal-based testing regimes, creating a major bottleneck for clinical translation. In vitro approaches to address this challenge have been limited in scalability and broad applicability. Here, we present a bacteria-in-spheroid coculture (BSCC) platform that simultaneously tests host species, therapeutic payloads, and synthetic gene circuits of engineered bacteria within multicellular spheroids over a timescale of weeks. Long-term monitoring of bacterial dynamics and disease progression enables quantitative comparison of critical therapeutic parameters such as efficacy and biocontainment. Specifically, we screen Salmonella typhimurium strains expressing and delivering a library of antitumor therapeutic molecules via several synthetic gene circuits. We identify candidates exhibiting significant tumor reduction and demonstrate high similarity in their efficacies, using a syngeneic mouse model. Last, we show that our platform can be expanded to dynamically profile diverse microbial species including Listeria monocytogenes, Proteus mirabilis, and Escherichia coli in various host cell types. This high-throughput framework may serve to accelerate synthetic biology for clinical applications and for understanding the host-microbe interactions in disease sites.
null
BACTERIA;CANCER;CELLS;DRUG;INVASION;SALMONELLA-TYPHIMURIUM
1
null
bacterial therapy;cancer therapy;high-throughput screening;Synthetic biology
6
BACTERIA;bacterial therapy;CANCER;cancer therapy;CELLS;DRUG;high-throughput screening;INVASION;SALMONELLA-TYPHIMURIUM;Synthetic biology
WOS:000466446500054
Columbia Univ, New York, NY USA;Univ Calif San Diego, La Jolla, CA USA
USA
2,019
null
0000-0001-8859-7494;0009-0009-8032-7487
null
null
English
null
BIOTECHNOL BIOENG;CANCER RES;CELL;CURR GENE THER;CURR OPIN BIOTECH;Curr Opin Syst Biol;EXP ANIM TOKYO;GASTROENTEROLOGY;GENE THER;J AM COLL SURGEONS;J CLIN ONCOL;J MOL BIOL;J R SOC INTERFACE;JOVE-J VIS EXP;MED SCI MONITOR;METHOD ENZYMOL;MICROB CELL FACT;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT MICROBIOL;NAT PROTOC;NAT REV CANCER;NAT REV MICROBIOL;NATURE;ONCOTARGET;P NATL ACAD SCI USA;PLOS ONE;SCI REP-UK;SCI TRANSL MED;SCIENCE;SLAS DISCOV;TOXINS;VACCINE
Castro, Samuel;Danino, Tal;Harimoto, Tetsuhiro;Hinchliffe, Taylor E;Mather, William;Singer, Zakary S;Velazquez, Oscar S;Zhang, Joanna
2024-03-11 ER
Al-Lazikani, B;Anderson, J C;Bartfeld, S;Bhatia, S N;Bhave, M S;Breslin, S;Chien Tiffany;Clevers, H;Daeffler, K N M;Dang, L H;Danino, T;Din, M O;Edwards, A M;Elsinghorst, E A;Fang, Y;Forbes, N S;Friedrich, J;Goers, L;Gopalakrishnan, V;Hohmann, E L;Hoiseth, S K;Hwang, I Y;Isabella, V M;Kasinskas, R W;Khademhosseini, A;Kim, H J;Lee, J W;Li, W Y;Liu, X D;Liu, Y;Mao, N;Nielsen, A A K;Osswald, A;Riglar, D T;Ryan, R M;Scott, S R;Shah, S A;Swofford, C A;Tangney, M;Teixeira, A P;Toso, J F;Verherstraeten, S;Weinberg, B H;Westphal, K;Yamada, T;Zhang, H;Zheng, D W;Zheng, J H
HW1MH
New York, NY USA;New York, NY USA.
29
null
2
null
30,996,123
Castro, Samuel;Danino, Tal;Harimoto, Tetsuhiro;Hinchliffe, Taylor E;Mather, William;Singer, Zakary S;Velazquez, Oscar S;Zhang, Joanna
P NATL ACAD SCI USA
La Jolla, CA USA;New York, NY USA
Connot, C;Haynes, K A;Livingstone, X;Lopez, B;Mani, A;Smith, C L;Tekel, S J
10.3389/fbioe.2019.00080
80
AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
k26372ne1g1o431k6633313a695i3l5l4c29v
Engineered Orthogonal Quorum Sensing Systems for Synthetic Gene Regulation in <i>Escherichia coil</i>
Arizona State Univ
null
Haynes, KA (corresponding author), Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA.;Haynes, KA (corresponding author), Emory Univ, WH Coulter Dept Biomed Engn, Atlanta, GA 30322 USA.
null
Connot, Christopher;Haynes, Karmella A;Livingstone, Xylaan;Lopez, Brianna;Mani, Amber;Smith, Christina L;Tekel, Stefan J
Biotechnology & Applied Microbiology;Engineering, Biomedical
Kern Entrepreneurial Engineering Network (KEEN) student research grant (Arizona State University); Fulton Undergraduate Research Initiative (FURI); Western Alliance to Expand Student Opportunities (WAESO, NSF) [HRD 1401190]; School of Biological and Health Systems Engineering (SBHSE)
WOS
Haynes, K A
Arizona State Univ, Tempe, AZ USA;Emory Univ, Atlanta, GA USA
7
<i>Escherichia;coil</i>;engineered;for;gene;in;Orthogonal;Quorum;regulation;Sensing;synthetic;systems
1
Haynes, Karmella
FRONTIERS MEDIA SA
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA;Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA.; Haynes, KA (corresponding author), Emory Univ, WH Coulter Dept Biomed Engn, Atlanta, GA 30322 USA;Arizona State Univ, Sch Life Sci, Tempe, AZ USA;Emory Univ, WH Coulter Dept Biomed Engn, Atlanta, GA 30322 USA
Article
Arizona State Univ;Emory Univ
LAUSANNE
null
null
Arizona State Univ;Emory Univ
Fulton Undergraduate Research Initiative (FURI);Kern Entrepreneurial Engineering Network (KEEN) student research grant (Arizona State University);School of Biological and Health Systems Engineering (SBHSE);Western Alliance to Expand Student Opportunities (WAESO, NSF)
Haynes, KA (corresponding author), Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA.; Haynes, KA (corresponding author), Emory Univ, WH Coulter Dept Biomed Engn, Atlanta, GA 30322 USA.
null
Connot, Christopher;Haynes, Karmella A;Livingstone, Xylaan;Lopez, Brianna;Mani, Amber;Smith, Christina L;Tekel, Stefan J
26
3
465,358,800,001
Fulton Undergraduate Research Initiative (FURI);Kern Entrepreneurial Engineering Network (KEEN) student research grant (Arizona State University);School of Biological and Health Systems Engineering (SBHSE);Western Alliance to Expand Student Opportunities (WAESO, NSF) [HRD 1401190]
USA
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
USA;USA.;
null
null
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA
2296-4185
Connot, C;Haynes, K A;Livingstone, X;Lopez, B;Mani, A;Smith, C L;Tekel, S J
APR 17
kahayne@emory.edu
<i>Escherichia coil</i>;Orthogonal Quorum Sensing Systems;Synthetic Gene Regulation
7
J
Biotechnology & Applied Microbiology;Engineering
10 distinct HSL-synthase enzymes;<i>Escherichia coil</i>;AubR);autoinducer;BACTERIA;Biosensor;BjaR;building synthetic gene;characterized components;CIRCUITS;coordinate behaviors across populations;crosstalk;current study;engineering microbial communities;EsaI/TraR;EsaI/TraR);Escherichia coli BL21;exhibit little;faults;five different regulators (LuxR;gene circuit;gene regulators;homoserine lactone;homoserine lactones (HSLs);identified two sets;investigation;LasI/LasR;LASR;lead;liquid;little;membrane-permeable compounds;microbial quorum signaling pathways;multiple regulators;natural DNA;networks;Orthogonal Quorum Sensing Systems;orthogonal synthase-regulator pairs (BjaI/BjaR;parallel signaling pathways;PATHWAY;popular tools;previous work;protein elements;PSEUDOMONAS-AERUGINOSA;quorum sensing;quorum sensing components;response;responses;results;same set;single HSL;single regulator (LuxR);solid cultures;synthases;Synthetic Gene Regulation;synthetic HSL-signaling systems;synthetic pathways;toolbox;transcription factor;TraR
Tekel, S J
AUTOINDUCER;BACTERIA;Biosensor;CIRCUITS;gene circuit;homoserine lactone;LASR;PATHWAY;PSEUDOMONAS-AERUGINOSA;quorum sensing;transcription factor
null
[Tekel, Stefan J.; Smith, Christina L.; Haynes, Karmella A.] Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA. [Lopez, Brianna; Mani, Amber; Connot, Christopher; Livingstone, Xylaan] Arizona State Univ, Sch Life Sci, Tempe, AZ USA. [Haynes, Karmella A.] Emory Univ, WH Coulter Dept Biomed Engn, Atlanta, GA 30322 USA.
This project was supported by a Kern Entrepreneurial Engineering Network (KEEN) student research grant (Arizona State University). BL, CS, and AM were supported by the Fulton Undergraduate Research Initiative (FURI). XL was supported by the Western Alliance to Expand Student Opportunities (WAESO, NSF Grant HRD 1401190). ST was supported by the School of Biological and Health Systems Engineering (SBHSE). DNA synthesis and primers were generously provided by Integrated DNA Technologies (IDT) as support for the 2017 International Genetically Engineered Machines (iGEM) competition.
10 distinct HSL-synthase enzymes;AubR);bacteria;BjaR;building synthetic gene;characterized components;coordinate behaviors across populations;crosstalk;current study;engineering microbial communities;EsaI/TraR;EsaI/TraR);Escherichia coli BL21;exhibit little;faults;five different regulators (LuxR;gene regulators;homoserine lactones (HSLs);identified two sets;investigation;LasI/LasR;LasR;lead;liquid;little;membrane-permeable compounds;microbial quorum signaling pathways;multiple regulators;natural DNA;networks;orthogonal synthase-regulator pairs (BjaI/BjaR;parallel signaling pathways;popular tools;previous work;protein elements;quorum sensing components;response;responses;results;same set;single HSL;single regulator (LuxR);solid cultures;synthases;synthetic HSL-signaling systems;synthetic pathways;toolbox;TraR
10.1016/j.bios.2012.08.011;10.1016/j.chembiol.2009.09.001;10.1016/j.chembiol.2014.10.008;10.1021/acssynbio.5b00286;10.1021/acssynbio.7b00058;10.1021/acssynbio.8b00271;10.1038/msb.2008.24;10.1038/nature03461;10.1038/nature07088;10.1038/nature09565;10.1038/nbt.3796;10.1038/nbt1413;10.1038/nmicrobiol.2017.83;10.1038/nrm907;10.1073/pnas.1103821108;10.1073/pnas.1114125108;10.1093/nar/gku1388;10.1126/science.1166253;10.1126/science.272.5268.1655;10.1128/AEM.00499-10;10.1128/JB.177.17.5000-5008.1995;10.1128/jb.179.18.5756-5767.1997;10.1128/JB.184.20.5686-5695.2002;10.1128/JB.185.20.5976-5983.2003;10.1128/JB.187.14.5054-5058.2005;10.1186/s12934-015-0379-1;10.1371/journal.pone.0202294;10.1371/journal.ppat.1006504;10.3389/fbioe.2015.00030
Arizona State Univ
Connot, C;Haynes, K A;Livingstone, X;Lopez, B;Mani, A;Smith, C L;Tekel, S J
Tekel, S J: Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA
null
HRD 1401190
29
null
USA
Arizona State Univ;Emory Univ
Tekel, Stefan J
Green Submitted, Green Published, gold
AUTOINDUCER;BACTERIA;BIOSENSOR;CIRCUITS;HOMOSERINE LACTONE;LASR;PATHWAY;PSEUDOMONAS-AERUGINOSA
Tekel, Stefan J.; Smith, Christina L.; Lopez, Brianna; Mani, Amber; Connot, Christopher; Livingstone, Xylaan; Haynes, Karmella A.;
null
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA;Arizona State Univ, Sch Life Sci, Tempe, AZ USA;Emory Univ, WH Coulter Dept Biomed Engn, Atlanta, GA 30322 USA
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA;Arizona State Univ, Sch Life Sci, Tempe, AZ USA;Emory Univ, WH Coulter Dept Biomed Engn, Atlanta, GA 30322 USA
null
Biosensor;Gene circuits;homoserine lactone;quorum sensing;transcription factor
null
1995;1996;1997;2002;2003;2005;2008;2009;2010;2011;2013;2014;2015;2016;2017;2018
15
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA;Emory Univ, WH Coulter Dept Biomed Engn, Atlanta, GA 30322 USA
Front. Bioeng. Biotechnol.
Haynes, Karmella A
FRONTIERS MEDIA SA
(BjaI/BjaR;(HSLs);(LuxR;(LuxR);+;,;10;a;across;activate;an;and;are;AubR);bacteria;become;behaviors;BjaR;BL21;building;by;called;can;characterized;coli;communities;components;composed;compounds;controlled;coordinate;crosstalk;cultures;current;derived;determined;different;distinct;DNA;elements;engineered;engineering;enzymes;EsaI/TraR;EsaI/TraR);Escherichia;exhibit;expand;expressed;faults;five;for;from;gene;have;here;homoserine;HSL;HSL-signaling;HSL-synthase;identified;identify;in;investigation;lactones;LasI/LasR;LasR;lead;liquid;little;membrane-permeable;microbial;multiple;natural;networks;no;of;Orthogonal;our;pairs;parallel;pathways;popular;populations;previous;protein;quorum;regulator;regulators;report;response;responses;results;same;sensing;set;sets;show;signaling;single;solid;study;synthase-regulator;synthases;synthetic;systems;that;the;these;they;to;toolbox;tools;TraR;two;we;when;where;work
Arizona State Univ;Emory Univ
Gene regulators that are controlled by membrane-permeable compounds called homoserine lactones (HSLs) have become popular tools for building synthetic gene networks that coordinate behaviors across populations of engineered bacteria. Synthetic HSL-signaling systems are derived from natural DNA and protein elements from microbial quorum signaling pathways. Crosstalk, where a single HSL can activate multiple regulators, can lead to faults in networks composed of parallel signaling pathways. Here, we report an investigation of quorum sensing components to identify synthetic pathways that exhibit little to no crosstalk in liquid and solid cultures. In previous work, we characterized the response of a single regulator (LuxR) to 10 distinct HSL-synthase enzymes. Our current study determined the responses of five different regulators (LuxR, LasR, TraR, BjaR, and AubR) to the same set of synthases. We identified two sets of orthogonal synthase-regulator pairs (BjaI/BjaR + EsaI/TraR and LasI/LasR + EsaI/TraR) that show little to no crosstalk when they are expressed in Escherichia coli BL21. These results expand the toolbox of characterized components for engineering microbial communities.
null
AUTOINDUCER;BACTERIA;BIOSENSOR;CIRCUITS;HOMOSERINE LACTONE;LASR;PATHWAY;PSEUDOMONAS-AERUGINOSA
2
null
Biosensor;gene circuit;homoserine lactone;quorum sensing;transcription factor
12
PSEUDOMONAS-AERUGINOSA;AUTOINDUCER;BACTERIA;Biosensor;CIRCUITS;Gene circuits;homoserine lactone;LASR;PATHWAY;quorum sensing;transcription factor
WOS:000465358800001
Arizona State Univ, Tempe, AZ USA;Emory Univ, Atlanta, GA USA
USA
2,019
null
0000-0002-5975-577X
null
null
English
null
ACS SYNTH BIOL;APPL ENVIRON MICROB;BIOSENS BIOELECTRON;CHEM BIOL;FRONT BIOENG BIOTECH;J BACTERIOL;MICROB CELL FACT;MOL SYST BIOL;NAT BIOTECHNOL;NAT MICROBIOL;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;PLOS PATHOG;SCIENCE
Connot, Christopher;Haynes, Karmella A;Livingstone, Xylaan;Lopez, Brianna;Mani, Amber;Smith, Christina L;Tekel, Stefan J
2024-03-11 ER
Ahlgren, N A;Balagadde, F K;Basu, S;Borlee, B R;Canton, B;Daer, R;Davis, R M;Fuqua, C;Gupta, A;Jayaraman, P;Kang, S Y;Kim, S;Lindemann, A;Lindsay, A;Marketon, M M;Medina, G;More, M I;Mukherjee, S;Pearson, J P;Schaefer, A L;Scott, S R;Tamsir, A;Taylor, A F;Vonbodman, S B;Wang, B J;Wu, F Q;Zou, Y Z
HU5ZQ
Atlanta, GA USA;Tempe, AZ USA.
18
null
2
null
31,058,147
Connot, Christopher;Haynes, Karmella A;Livingstone, Xylaan;Lopez, Brianna;Mani, Amber;Smith, Christina L;Tekel, Stefan J
FRONT BIOENG BIOTECH
Atlanta, GA USA;Tempe, AZ USA
Armstrong, Z;Chen, H M;Hallam, S J;Liu, F;Withers, S G
10.1021/acscatal.8b05179
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
3e4c6p2m1x5j4y1v5y3m5e2m1p6q247291d3y6t
Systematic Screening of Synthetic Gene-Encoded Enzymes for Synthesis of Modified Glycosides
Univ British Columbia
null
Withers, SG (corresponding author), Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.;Withers, SG (corresponding author), Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.;Withers, SG (corresponding author), Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada.;Withers, SG (corresponding author), Univ British Columbia, Michael Smith Lab, Ctr High Throughput Biol, Vancouver, BC V6T 1Z3, Canada.
null
Armstrong, Zachary;Chen, Hong-Ming;Hallam, Steven J;Liu, Feng;Withers, Stephen G
Chemistry, Physical
Natural Sciences and Engineering Research Council of Canada (NSERC) [DE-AC02-05CH1123]
WOS
Withers, S G
Univ British Columbia, Vancouver BC, Canada
9
Enzymes;for;Gene-Encoded;Glycosides;modified;of;screening;synthesis;synthetic;systematic
1
Armstrong, Zachary;Withers, Stephen G
AMER CHEMICAL SOC
Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada;Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z1, Canada;Univ British Columbia, ECOSCOPE Training Program, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada;Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada.; Withers, SG (corresponding author), Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.; Withers, SG (corresponding author), Univ British Columbia, Michael Smith Lab, Ctr High Throughput Biol, Vancouver, BC V6T 1Z3, Canada.; Withers, SG (corresponding author), Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Grad Program Bioinformat, Vancouver, BC V6T 1Z4, Canada;Univ British Columbia, Michael Smith Lab, Ctr High Throughput Biol, Vancouver, BC V6T 1Z3, Canada
Article
Univ British Columbia
WASHINGTON
null
null
Univ British Columbia
Natural Sciences and Engineering Research Council of Canada (NSERC)
Withers, SG (corresponding author), Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada.; Withers, SG (corresponding author), Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.; Withers, SG (corresponding author), Univ British Columbia, Michael Smith Lab, Ctr High Throughput Biol, Vancouver, BC V6T 1Z3, Canada.; Withers, SG (corresponding author), Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
3227
Armstrong, Zachary;Chen, Hong-Ming;Hallam, Steven J;Liu, Feng;Withers, Stephen G
51
7
464,075,700,049
Natural Sciences and Engineering Research Council of Canada (NSERC) [DE-AC02-05CH1123]
Canada
ACS CATALYSIS
Canada
null
null
Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada
2155-5435
Armstrong, Z;Chen, H M;Hallam, S J;Liu, F;Withers, S G
APR
withers@chem.ubc.ca
Modified Glycosides;synthesis;Synthetic Gene-Encoded Enzymes;systematic Screening
5
J
Chemistry
-azido derivatives;1;175 synthetic genes;3-;4-;6-amino;6-positions;active;activity-based probes;alanine;alpha-glucosyl fluoride;amino-;approaches;assembly;azido-glucosides;beta-glucosidase;biocatalysis;carbohydrate-active enzymes;catalysts;catalytic nucleophile glutamate;CAZymes;CHEMOENZYMATIC SYNTHESIS;cloning;creation;detailed kinetic analysis;directed evolution;E. coli clones;eight;enzymes;FAMILY-1;gene products;general framework;glycine;glycolipid analogues;glycosidases;glycoside hydrolase;glycoside hydrolase family GH1;glycosidehydrolase-containing clone libraries;glycosynthase;high-throughput functional screening;hydrolysis;IDENTIFICATION;library;mechanism;Modified Glycosides;modified sugars;mutants;opens;phylogenetically diverse libraries;phylogenomic library;plate-based aglycone specificity screening;rapid evaluation;rare catalytic capabilities;screening;sequence-based family;serine;seven;several useful biocatalysts;subfamilies;subset;substrate specificity;synthesis;synthetic capabilities;Synthetic Gene-Encoded Enzymes;synthetic genes;systematic Screening;taggable disaccharides;three glycosynthase mutants;transfer;trisaccharides;utility
Armstrong, Z
BETA-GLUCOSIDASE;biocatalysis;CAZymes;CHEMOENZYMATIC SYNTHESIS;cloning;directed evolution;FAMILY-1;glycoside hydrolase;glycosynthase;high-throughput functional screening;MECHANISM;phylogenomic library
3219
[Armstrong, Zachary; Hallam, Steven J.; Withers, Stephen G.] Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada. [Liu, Feng; Chen, Hong-Ming; Withers, Stephen G.] Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. [Hallam, Steven J.] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z1, Canada. [Hallam, Steven J.] Univ British Columbia, Grad Program Bioinformat, Vancouver, BC V6T 1Z4, Canada. [Withers, Stephen G.] Univ British Columbia, Michael Smith Lab, Ctr High Throughput Biol, Vancouver, BC V6T 1Z3, Canada. [Withers, Stephen G.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. [Hallam, Steven J.] Univ British Columbia, ECOSCOPE Training Program, Vancouver, BC V6T 1Z3, Canada.
We thank the Natural Sciences and Engineering Research Council of Canada (NSERC) for Discovery grants to S.G.W. and S.J.H. We also thank the Joint Genome Institute for provision of the GH1 gene library that was synthesized under Contract No. DE-AC02-05CH1123.
-azido derivatives;1;175 synthetic genes;3-;4-;6-amino;6-positions;active;activity-based probes;alanine;alpha-glucosyl fluoride;amino-;approaches;assembly;azido-glucosides;carbohydrate-active enzymes;catalysts;catalytic nucleophile glutamate;creation;detailed kinetic analysis;E. coli clones;eight;enzymes;gene products;general framework;glycine;glycolipid analogues;glycosidases;glycoside hydrolase family GH1;glycosidehydrolase-containing clone libraries;hydrolysis;identification;library;modified sugars;mutants;opens;phylogenetically diverse libraries;plate-based aglycone specificity screening;rapid evaluation;rare catalytic capabilities;screening;sequence-based family;serine;seven;several useful biocatalysts;subfamilies;subset;substrate specificity;synthetic capabilities;synthetic genes;taggable disaccharides;three glycosynthase mutants;transfer;trisaccharides;utility
10.1002/1873-3468.12059;10.1002/adsc.201100461;10.1002/anie.201204578;10.1002/anie.201810661;10.1002/bip.22335;10.1002/cbic.201100229;10.1002/ejoc.201402588;10.1007/s00253-006-0526-z;10.1007/s002840010220;10.1016/bs.mie.2017.06.001;10.1016/j.carres.2006.04.049;10.1016/j.carres.2012.02.013;10.1016/j.carres.2018.07.007;10.1016/j.cbpa.2015.06.032;10.1016/j.copbio.2011.02.010;10.1016/j.febslet.2007.03.009;10.1016/j.pep.2005.01.016;10.1016/j.sbi.2009.08.003;10.1016/S1074-5521(01)00038-2;10.1021/acs.chemrev.8b00066;10.1021/acschembio.6b00340;10.1021/bi00049a035;10.1021/bm900215p;10.1021/cb500244v;10.1021/ja00104a060;10.1021/ja00258a047;10.1021/ja980833d;10.1038/nature11117;10.1038/nchembio.203;10.1038/ncomms12482;10.1038/NMETH899;10.1039/c7cc04380e;10.1074/jbc.M116.721597;10.1074/jbc.M406890200;10.1101/gr.108332.110;10.1146/annurev-biochem-062917-012034;10.1371/journal.pone.0132848;10.3389/fmicb.2015.01291;[10.3389/frricb.2015.00275, 10.3389/fmicb.2015.00275]
Univ British Columbia
Armstrong, Z;Chen, H M;Hallam, S J;Liu, F;Withers, S G
Armstrong, Z: Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada
Armstrong, Zachary;Withers, Stephen G
DE-AC02-05CH1123
40
null
Canada
Univ British Columbia
Armstrong, Zachary
null
BETA-GLUCOSIDASE;CHEMOENZYMATIC SYNTHESIS;CLONING;DIRECTED EVOLUTION;FAMILY-1;GLYCOSYNTHASE;MECHANISM
Armstrong, Zachary; Liu, Feng; Chen, Hong-Ming; Hallam, Steven J.; Withers, Stephen G.;
null
Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada;Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z1, Canada;Univ British Columbia, ECOSCOPE Training Program, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada;Univ British Columbia, Grad Program Bioinformat, Vancouver, BC V6T 1Z4, Canada;Univ British Columbia, Michael Smith Lab, Ctr High Throughput Biol, Vancouver, BC V6T 1Z3, Canada
Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada;Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z1, Canada;Univ British Columbia, ECOSCOPE Training Program, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada;Univ British Columbia, Grad Program Bioinformat, Vancouver, BC V6T 1Z4, Canada;Univ British Columbia, Michael Smith Lab, Ctr High Throughput Biol, Vancouver, BC V6T 1Z3, Canada
null
biocatalysis;CAZymes;glycoside hydrolase;glycosynthase;high-throughput functional screening;phylogenomic library
4
1987;1994;1995;1998;2001;2004;2005;2006;2007;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
15
Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada;Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada;Univ British Columbia, Genome Sci & Technol Program, 2329 West Mall, Vancouver, BC V6T 1Z4, Canada;Univ British Columbia, Michael Smith Lab, Ctr High Throughput Biol, Vancouver, BC V6T 1Z3, Canada
ACS Catal.
Withers, Stephen G
AMER CHEMICAL SOC
,;-azido;1;175;3-;4-;6-amino;6-positions;a;active;activity-based;aglycone;alanine;allows;alpha-glucosyl;also;amino-;analogues;analysis;and;approaches;are;as;assembly;at;azido-glucosides;be;biocatalysts;by;can;capabilities;capable;carbohydrate-active;catalysts;catalytic;catalyzing;characterized;cleave;clone;clones;coli;construction;creation;demonstrated;derivatives;detailed;develop;disaccharides;diverse;does;E.;each;eight;encoded;enzymes;evaluation;exploited;explored;family;fluoride;for;framework;from;further;gene;general;generated;genes;GH1;glutamate;glycine;glycolipid;glycosidases;glycoside;glycosidehydrolase-containing;glycosynthase;harboring;herein;hydrolase;hydrolysis;identification;identify;in;it;kinetic;large;libraries;library;modified;most;mutants;not;nucleophile;of;only;opens;or;other;phylogenetically;plate-based;present;probes;products;provides;rapid;rare;report;represent;screening;search;sequence-based;serine;seven;several;specificity;subfamilies;subset;substituted;substrate;such;sugars;synthetic;taggable;that;the;their;then;these;this;three;through;to;transfer;trisaccharides;up;useful;utility;was;we;were;which;with;within;work
Univ British Columbia
The construction of large, phylogenetically diverse libraries of synthetic genes from a sequence-based family allows rapid evaluation of the substrate specificity encoded within the gene products and identification of rare catalytic capabilities. For carbohydrate-active enzymes such as glycosidases, this opens up approaches to search for enzymes that are capable of catalyzing the hydrolysis and transfer of modified sugars. Herein we report the screening of a library of E. coli clones each harboring 1 of 175 synthetic genes that represent the subfamilies within the glycoside hydrolase family GH1 to identify a subset of enzymes that cleave amino- and azido-glucosides modified at the 3-, 4-, and 6-positions. Eight of the most active such enzymes were further characterized through detailed kinetic analysis and plate-based aglycone specificity screening. Three glycosynthase mutants of each of these enzymes were generated, in which their catalytic nucleophile glutamate was substituted by alanine, glycine, or serine, and their synthetic capabilities were explored with alpha-glucosyl fluoride and 3-, 4-, and 6-amino and -azido derivatives. The utility of seven of the generated mutants was then demonstrated through the assembly of taggable disaccharides, trisaccharides, glycolipid analogues, and activity-based probes. Not only does this work present the creation of several useful biocatalysts, it also provides a general framework that can be exploited to develop catalysts from other glycosidehydrolase-containing clone libraries.
I-7229-2019;U-3635-2019
BETA-GLUCOSIDASE;CHEMOENZYMATIC SYNTHESIS;CLONING;DIRECTED EVOLUTION;FAMILY-1;GLYCOSYNTHASE;MECHANISM
1
null
biocatalysis;CAZymes;glycoside hydrolase;glycosynthase;high-throughput functional screening;phylogenomic library
17
BETA-GLUCOSIDASE;biocatalysis;CAZymes;CHEMOENZYMATIC SYNTHESIS;cloning;directed evolution;family 1;glycoside hydrolase;glycosynthase;high-throughput functional screening;MECHANISM;phylogenomic library
WOS:000464075700049
Univ British Columbia, Vancouver BC, Canada
Canada
2,019
null
0000-0002-4086-2946;0000-0002-6722-5701
null
null
English
null
ACS CHEM BIOL;ADV SYNTH CATAL;ANGEW CHEM INT EDIT;ANNU REV BIOCHEM;APPL MICROBIOL BIOT;BIOCHEMISTRY-US;BIOMACROMOLECULES;BIOPOLYMERS;CARBOHYD RES;CHEM BIOL;CHEM COMMUN;CHEM REV;CHEMBIOCHEM;CURR MICROBIOL;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;CURR OPIN STRUC BIOL;EUR J ORG CHEM;EXTREMOPHILES;FEBS LETT;FRONT MICROBIOL;GENOME RES;J AM CHEM SOC;J BIOL CHEM;METHOD ENZYMOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NATURE;PLOS ONE;PROTEIN EXPRES PURIF
Armstrong, Zachary;Chen, Hong-Ming;Hallam, Steven J;Liu, Feng;Withers, Stephen G
2024-03-11 ER
Aharoni, A;Armstrong, Z;Blanchard, J E;Bornscheuer, U T;Chen, H M;Cobucci-Ponzano, B;Danby, P M;Faijes, M;Giddens, J P;Goddard-Borger, E D;Gullfot, F;Hahm, H S;Heins, R A;Kim, Y W;Kurogochi, M;Kwan, D H;Lauro, B D;Leis, B;Li, K Y;López-López, O;Mackenzie, L F;Namchuk, M N;Naresh, K;Nijikken, Y;Pengthaisong, S;Rich, J R;Spiridonov, N A;Studier, F W;Tasse, L;Taupp, M;Tokuriki, N;Tsukada, T;Turner, N J;Wang, Q P;Wen, L Q;Withers, S G;Zeymer, C;Zhang, J B
HS7UV
Vancouver BC, Canada;Vancouver BC, Canada.
15
null
1
null
null
Armstrong, Zachary;Chen, Hong-Ming;Hallam, Steven J;Liu, Feng;Withers, Stephen G
ACS CATAL
Vancouver BC, Canada
Li, W C;Wang, N;Zhang, J M;Zhang, W
10.1371/journal.pone.0213977
e0213977
1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
22584v3ul5w1g2v4z1341q6v5j62582b623q2f
Optimal parameter identification of synthetic gene networks using harmony search algorithm
Zhejiang Univ
null
Zhang, JM (corresponding author), Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China.
null
Li, Wenchao;Wang, Ning;Zhang, Jianming;Zhang, Wei
Multidisciplinary Sciences
National Natural Science Foundation of China (CN) [61573311]
WOS
Zhang, J M
Zhejiang Univ, Zhejiang, Peoples R China
14
algorithm;gene;harmony;Identification;networks;of;optimal;parameter;search;synthetic;using
1
Li, Wenchao
PUBLIC LIBRARY SCIENCE
Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China
Article
Zhejiang Univ
SAN FRANCISCO
null
null
Zhejiang Univ
National Natural Science Foundation of China (CN)
Zhang, JM (corresponding author), Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China.
null
Li, Wenchao;Wang, Ning;Zhang, Jianming;Zhang, Wei
10
1
462,732,300,008
National Natural Science Foundation of China (CN) [61573311]
China
PLOS ONE
China
null
null
Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China
1932-6203
Li, W C;Wang, N;Zhang, J M;Zhang, W
MAR 29
jmzhang@iipc.zju.edu.cn
harmony search algorithm;optimal parameter identification;synthetic gene networks
4
J
Science & Technology - Other Topics
account;analysis;challenged task;CIRCUITS;computational modeling;designed cost function takes two major factors;effectiveness;estimation accuracy;estimation errors;experimental costs;experiments select two types;expression;Gene circuits;Genetic circuits;harmony search algorithm;harmony search(HS)-based OED algorithm;identification outcomes;informative observations;input signals;maximizing Fisher information matrix(FIM)-based optimal criteria;measurement cost;modeling gene networks;MODELS;modified E-optimal criteria;number;optimal experimental design(OED) method;OPTIMAL EXPERIMENTAL-DESIGN;optimal inputs;optimal parameter identification;proposed HS-OED approach;proposed HS-OED method outperforms two candidate OED approaches;proposed optimal identification methodology;reduced computational effort;reliable model parameters;response behaviors;sample size;SELECTION;study focuses;synthetic gene networks;synthetic genetic networks;systems biology;time points;trade-off;two-stage optimization
Zhang, W
CIRCUITS;EXPRESSION;MODELS;OPTIMAL EXPERIMENTAL-DESIGN;SELECTION
null
[Zhang, Wei; Li, Wenchao; Zhang, Jianming; Wang, Ning] Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China.
Author Wei Zhang is partly supported by National Natural Science Foundation of China (CN) 61573311.
account;analysis;challenged task;computational modeling;designed cost function takes two major factors;effectiveness;estimation accuracy;estimation errors;experimental costs;experiments select two types;gene circuits;genetic circuits;harmony search(HS)-based OED algorithm;identification outcomes;informative observations;input signals;maximizing Fisher information matrix(FIM)-based optimal criteria;measurement cost;modeling gene networks;modified E-optimal criteria;number;optimal experimental design(OED) method;optimal inputs;proposed HS-OED approach;proposed HS-OED method outperforms two candidate OED approaches;proposed optimal identification methodology;reduced computational effort;reliable model parameters;response behaviors;sample size;study focuses;synthetic genetic networks;systems biology;time points;trade-off;two-stage optimization
10.1002/qre.1591;10.1007/s00158-015-1271-7;10.1016/0005-1098(90)90116-Y;10.1016/j.aml.2014.09.013;10.1016/j.bpj.2017.08.057;10.1016/j.cels.2017.01.003;10.1016/j.mbs.2012.01.001;10.1021/sb400139h;10.1038/nbt.3044;10.1038/nbt.4111;10.1038/nrg2102;10.1038/nrg3885;10.1038/s41564-017-0022-5;10.1038/s41580-018-0024-z;10.1042/BSE0450195;10.1093/bioinformatics/btn330;10.1093/bioinformatics/btp358;10.1093/bioinformatics/btt436;10.1093/bioinformatics/btv186;10.1093/bioinformatics/btv672;10.1093/nar/gkv1280;10.1093/synbio/ysx003;10.1109/ACC.2014.6858649;10.1109/TCBB.2014.2377733;10.1109/TMBMC.2016.2633265;10.1126/science.aal2052;10.1128/JB.157.1.283-290.1984;10.1177/003754970107600201;10.1177/0037549703040937;10.1186/1752-0509-1-51;10.1186/1752-0509-4-38;10.1186/1752-0509-8-13;10.1186/1752-0509-8-20;10.1186/1756-0500-5-518;10.1186/s12918-016-0328-6;10.1186/s12918-018-0594-6;10.1371/journal.pcbi.1000558;10.1371/journal.pcbi.1004706;10.1371/journal.pone.0110234;10.1371/journal.pone.0200094
Zhejiang Univ
Li, W C;Wang, N;Zhang, J M;Zhang, W
Zhang, W: Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China
null
61573311
40
null
China
Zhejiang Univ
Zhang, Wei
gold, Green Published, Green Submitted
CIRCUITS;EXPRESSION;MODELS;OPTIMAL EXPERIMENTAL-DESIGN;SELECTION
Zhang, Wei; Li, Wenchao; Zhang, Jianming; Wang, Ning;
null
Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China
Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China
null
null
3
1984;1990;2001;2003;2007;2008;2009;2010;2012;2013;2014;2015;2016;2017;2018
1
Zhejiang Univ, Dept Control & Engn, Inst Cyber Syst & Control, Hangzhou, Zhejiang, Peoples R China
PLoS One
Wang, Ning
PUBLIC LIBRARY SCIENCE
,;a;account;accuracy;algorithm;an;analysis;and;applies;approach;approaches;are;behaviors;between;biology;candidate;challenged;circuits;computational;cost;costs;criteria;describe;design(OED);designed;designs;E-optimal;effectiveness;effort;engineered;errors;estimation;experimental;experiments;factors;Fisher;focuses;function;furthermore;gene;genetic;harmony;HS-OED;identification;important;in;indicate;information;informative;input;inputs;into;involves;is;major;matrix(FIM)-based;maximizing;measurement;method;methodology;minimize;model;modeling;modified;networks;number;observations;obtain;OED;of;on;optimal;optimization;order;outcomes;outperforms;paper;parameters;points;predict;proportional;proposed;provide;pursue;reduced;reliable;response;sample;search(HS)-based;select;signals;size;study;synthetic;systems;takes;task;the;this;time;to;trade-off;two;two-stage;types;using;validate;which;while;with
Zhejiang Univ
Computational modeling of engineered gene circuits is an important while challenged task in systems biology. In order to describe and predict the response behaviors of genetic circuits using reliable model parameters, this paper applies an optimal experimental design(OED) method to obtain input signals. In order to obtain informative observations, this study focuses on maximizing Fisher information matrix(FIM)-based optimal criteria and to provide optimal inputs. Furthermore, this paper designs a two-stage optimization with the modified E-optimal criteria and applies harmony search(HS)-based OED algorithm to minimize estimation errors. The proposed optimal identification methodology involves estimation errors and the sample size to pursue a trade-off between estimation accuracy and measurement cost in modeling gene networks. The designed cost function takes two major factors into account, in which experimental costs are proportional to the number of time points. Experiments select two types of synthetic genetic networks to validate the effectiveness of the proposed HS-OED approach. Identification outcomes and analysis indicate the proposed HS-OED method outperforms two candidate OED approaches, with reduced computational effort.
null
CIRCUITS;EXPRESSION;MODEL;OPTIMAL EXPERIMENTAL-DESIGN;SELECTION
0
null
null
28
CIRCUITS;EXPRESSION;MODEL;Optimal experimental design;SELECTION
WOS:000462732300008
Zhejiang Univ, Zhejiang, Peoples R China
China
2,019
null
0000-0002-7956-0742
null
null
English
null
ACS SYNTH BIOL;APPL MATH LETT;AUTOMATICA;BIOINFORMATICS;BIOPHYS J;BMC Res Notes;BMC SYST BIOL;CELL SYST;ESSAYS BIOCHEM;IEEE ACM T COMPUT BI;IEEE T MOL BIO MULT;J BACTERIOL;MATH BIOSCI;NAT BIOTECHNOL;NAT MICROBIOL;NAT REV GENET;NAT REV MOL CELL BIO;NUCLEIC ACIDS RES;P AMER CONTR CONF;PLOS COMPUT BIOL;PLOS ONE;QUAL RELIAB ENG INT;SCIENCE;SIMUL-T SOC MOD SIM;SIMULATION;STRUCT MULTIDISCIP O;SYN BIOL
Li, Wenchao;Wang, Ning;Zhang, Jianming;Zhang, Wei
2024-03-11 ER
Adoteye, K;Alon, U;Bandara, S;Banga, J R;Bouffier, A M;Busetto, A G;Carbonell-Ballestero, M;Dehghannasiri, R;Faller, D;Firman, T;Futcher, A B;Geem, Z W;Huang, B;Huynh, L;Le Novère, N;Liao, C;Lin, C D;Liu, Z;Llamosi, A;Mangan Nm.;Marchisio, M A;Meyer, P;Mishra, D;Mohammadi, P;Mélykúti, B;Nimmegeers, P;O'Brien, E L;Pirgazi, J;Raue, A;Segall-Shapiro, T H;Srinivas, N;Steinke, F;Stigter Johannes, D;Ud-Dean, S M M;Vanlier, J;Walter, E;Wilson, A D;Xie, M Q;Yamazaki, K;Zhu, F
HQ9FO
Zhejiang, Peoples R China
1
null
1
null
30,925,150
Li, Wenchao;Wang, Ning;Zhang, Jianming;Zhang, Wei
PLOS ONE
Zhejiang, Peoples R China
Ayukawa, S;Kiga, D;Moriya, T;Wakao, S;Wakayama, Y;Yamamura, M;Yamaoka, T;Zhang, Z C
10.3390/life9010030
30
ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
215i1i2i2f575r2l1u5y382k6d1j4i354r1i4x6g
Comparison between Effects of Retroactivity and Resource Competition upon Change in Downstream Reporter Genes of Synthetic Genetic Circuits
Tokyo Inst Technol
null
Kiga, D (corresponding author), Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan.;Kiga, D (corresponding author), Waseda Univ, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698050, Japan.
null
Ayukawa, Shotaro;Kiga, Daisuke;Moriya, Takefumi;Wakao, Shinji;Wakayama, Yuki;Yamamura, Masayuki;Yamaoka, Tomohiro;Zhang, Zicong
Biology;Microbiology
KAKENHI [23119005, 26540152, 15KT0148]; Commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterials from the Ministry of Economy, Trade, and Industry (METI); [12J09398]; Grants-in-Aid for Scientific Research [15KT0148, 26540152] Funding Source: KAKEN
WOS
Kiga, D
Tokyo Inst Technol, Kanagawa, Japan;Waseda Univ, Tokyo, Japan
9
and;between;Change;circuits;comparison;competition;Downstream;Effects;genes;genetic;in;of;Reporter;resource;Retroactivity;synthetic;upon
1
Kiga, Daisuke;Zhang, Zicong
MDPI
Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan;Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan.; Kiga, D (corresponding author), Waseda Univ, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698050, Japan;Waseda Univ, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698050, Japan;Waseda Univ, Waseda Res Inst Sci & Engn, Shinjuku Ku, Tokyo 1698050, Japan
Article
Tokyo Inst Technol;Waseda Univ
BASEL
null
null
Tokyo Inst Technol;Waseda Univ
Commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterials from the Ministry of Economy, Trade, and Industry (METI);Grants-in-Aid for Scientific Research;KAKENHI
Kiga, D (corresponding author), Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan.; Kiga, D (corresponding author), Waseda Univ, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698050, Japan.
null
Ayukawa, Shotaro;Kiga, Daisuke;Moriya, Takefumi;Wakao, Shinji;Wakayama, Yuki;Yamamura, Masayuki;Yamaoka, Tomohiro;Zhang, Zicong
3
3
464,133,600,001
[12J09398];Commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterials from the Ministry of Economy, Trade, and Industry (METI);Grants-in-Aid for Scientific Research [15KT0148, 26540152] Funding Source: KAKEN;KAKENHI [23119005, 26540152, 15KT0148]
Japan
LIFE-BASEL
Japan
null
null
Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan
null
Ayukawa, S;Kiga, D;Moriya, T;Wakao, S;Wakayama, Y;Yamamura, M;Yamaoka, T;Zhang, Z C
MAR 26
kiga@waseda.jp;mly-jp.klws@fuji.waseda.jp;my@c.titech.ac.jp;ru10-deka@suou.waseda.jp;shotaroayukawasb@gmail.com;tkfmmry@gmail.com;wakao@waseda.jp;zzhang@ali.c.titech.ac.jp
Change;Downstream Reporter Genes;Effects;Resource Competition;Retroactivity;synthetic genetic circuits
8
J
Life Sciences & Biomedicine - Other Topics;Microbiology
activity;advanced design;advancements;altogether;analyses;ARAC;BINDING;cell;Change;circuits' components;combination;competition;component;control;corresponding gene;DEGRADATION;degradation);different copy number;downstream gene;Downstream Reporter Genes;downstream reporter promoter;dual-feedback oscillator;Effects;ESCHERICHIA-COLI;fluorescent protein reporter;Genetic circuits;molecular biology;OSCILLATIONS;phenomenon;protein-binding site;quantification;regulatory protein-binding sites;reporter gene;reporter gene activities;reporter genes;reporter promoters;reporters;resource competition;results;retroactivity;retroactivity (titration;SELECTION;silico;stability;studies;synthetic biology;synthetic genetic circuits;synthetic genetic oscillator;systems biology;two sources;unexpected effects;upstream dynamics;upstream protein;upstream regulatory genes;upstream regulatory protein;vivo experiments;vivo observations
Moriya, T
ARAC;CELL;ESCHERICHIA-COLI;OSCILLATIONS;protein-binding site;reporter gene;resource competition;retroactivity;Synthetic biology;systems biology
null
[Moriya, Takefumi; Zhang, Zicong; Yamamura, Masayuki; Kiga, Daisuke] Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan. [Yamaoka, Tomohiro; Wakayama, Yuki; Wakao, Shinji; Kiga, Daisuke] Waseda Univ, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698050, Japan. [Ayukawa, Shotaro] Waseda Univ, Waseda Res Inst Sci & Engn, Shinjuku Ku, Tokyo 1698050, Japan.
This work was supported by Grants-in-Aid for Japan Society for the Promotion of Science Fellows (No. 12J09398 to TM) and the KAKENHI programs (23119005 and 26540152 to DK and 15KT0148 to SA) and a grant from the Commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterials from the Ministry of Economy, Trade, and Industry (METI).
activity;advanced design;advancements;altogether;analyses;binding;cell;circuits' components;combination;competition;component;control;corresponding gene;degradation;degradation);different copy number;downstream gene;downstream reporter genes;downstream reporter promoter;dual-feedback oscillator;fluorescent protein reporter;genetic circuits;molecular biology;oscillations;phenomenon;quantification;regulatory protein-binding sites;reporter gene activities;reporter genes;reporter promoters;reporters;results;retroactivity;retroactivity (titration;selection;silico;stability;studies;synthetic biology;synthetic genetic circuits;synthetic genetic oscillator;two sources;unexpected effects;upstream dynamics;upstream protein;upstream regulatory genes;upstream regulatory protein;vivo experiments;vivo observations
10.1016/0378-1119(80)90100-6;10.1016/B978-0-12-391857-4.00009-4;10.1016/j.bpj.2010.09.057;10.1016/j.bpj.2010.12.3737;10.1016/j.cell.2014.02.022;10.1016/j.compchemeng.2004.08.035;10.1021/j100540a008;10.1021/sb300098w;10.1021/sb400102w;10.1038/35002125;10.1038/35002131;10.1038/msb.2011.94;10.1038/msb.2012.7;10.1038/msb4100204;10.1038/nature07389;10.1038/nature13238;10.1038/nature19841;10.1038/ncomms1687;10.1038/nmeth.2089;10.1073/pnas.1100060108;10.1073/pnas.1105901108;10.1073/pnas.1415685111;10.1073/pnas.83.18.6682;10.1093/nar/25.6.1203;10.1093/nar/8.22.5267;10.1093/nar/gkl393;10.1093/nar/gku735;10.1098/rsif.2018.0157;10.1103/PhysRevE.86.041920;10.1103/PhysRevLett.108.018102;10.1103/PhysRevLett.88.148101;10.1109/ACC.2016.7526834;10.1126/science.1070919;10.1126/science.8303295;10.1128/AEM.00791-07;10.1128/MCB.2.9.1044;10.1128/MCB.6.9.3173;10.1152/ajpcell.1998.274.2.C531;10.1186/1471-2164-11-S4-S16;10.1186/1752-0509-8-S4-S4;10.1186/1754-1611-2-5;10.1186/1754-1611-4-16;10.1371/journal.pbio.0060232;10.1371/journal.pcbi.1003486;10.1371/journal.pone.0041019;10.3389/fbioe.2014.00087
Tokyo Inst Technol
Ayukawa, S;Kiga, D;Moriya, T;Wakao, S;Wakayama, Y;Yamamura, M;Yamaoka, T;Zhang, Z C
Moriya, T: Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan
....., ....;Kiga, Daisuke;Wakao, Shinji;Zhang, Zicong
12J09398;15KT0148;23119005;26540152
50
null
Japan
Tokyo Inst Technol;Waseda Univ
Moriya, Takefumi
gold, Green Submitted, Green Published
ARAC;CELL;ESCHERICHIA-COLI;OSCILLATIONS
Moriya, Takefumi; Yamaoka, Tomohiro; Wakayama, Yuki; Ayukawa, Shotaro; Zhang, Zicong; Yamamura, Masayuki; Wakao, Shinji; Kiga, Daisuke;
null
Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan;Waseda Univ, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698050, Japan;Waseda Univ, Waseda Res Inst Sci & Engn, Shinjuku Ku, Tokyo 1698050, Japan
Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan;Waseda Univ, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698050, Japan;Waseda Univ, Waseda Res Inst Sci & Engn, Shinjuku Ku, Tokyo 1698050, Japan
2075-1729
protein-binding site;reporter gene;resource competition;retroactivity;Synthetic biology;systems biology
1
1961;1977;1980;1982;1986;1988;1994;1997;1998;2000;2002;2005;2006;2007;2008;2010;2011;2012;2013;2014;2015;2016;2018
2
Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268503, Japan;Waseda Univ, Dept Elect Engn & Biosci, Shinjuku Ku, Tokyo 1698050, Japan
Life-Basel
Kiga, Daisuke
MDPI
(titration;,;a;achieved;activities;activity;advanced;advancements;allows;altered;altogether;an;analyses;and;as;binding;biology;by;cell;circuits;circuits';combination;competing;competition;component;components;contributed;control;copy;corresponding;degradation;degradation);design;different;downstream;dual-feedback;dynamics;effects;ensure;essential;experiments;fluorescent;for;found;from;furthermore;gene;genes;genetic;have;however;important;in;indicate;interfere;is;level;may;molecular;number;observations;of;on;oscillations;oscillator;our;phenomenon;produced;promoter;promoters;protein;protein-binding;quantification;regulatory;reporter;reporters;results;retroactivity;selection;separating;showed;silico;sites;sources;stability;studies;suggesting;synthetic;termed;that;the;this;to;two;unexpected;upstream;using;vivo;we;with
Tokyo Inst Technol;Waseda Univ
Reporter genes have contributed to advancements in molecular biology. Binding of an upstream regulatory protein to a downstream reporter promoter allows quantification of the activity of the upstream protein produced from the corresponding gene. In studies of synthetic biology, analyses of reporter gene activities ensure control of the cell with synthetic genetic circuits, as achieved using a combination of in silico and in vivo experiments. However, unexpected effects of downstream reporter genes on upstream regulatory genes may interfere with in vivo observations. This phenomenon is termed as retroactivity. Using in silico and in vivo experiments, we found that a different copy number of regulatory protein-binding sites in a downstream gene altered the upstream dynamics, suggesting retroactivity of reporters in this synthetic genetic oscillator. Furthermore, by separating the two sources of retroactivity (titration of the component and competition for degradation), we showed that, in the dual-feedback oscillator, the level of the fluorescent protein reporter competing for degradation with the circuits' components is important for the stability of the oscillations. Altogether, our results indicate that the selection of reporter promoters using a combination of in silico and in vivo experiments is essential for the advanced design of genetic circuits.
HJI-0218-2023;O-1942-2018;T-5361-2018;V-8433-2019
ARAC;CELLS;ESCHERICHIA-COLI;OSCILLATIONS
0
null
protein-binding site;reporter gene;resource competition;retroactivity;Synthetic biology;systems biology
19
ESCHERICHIA-COLI;ARAC;CELLS;OSCILLATIONS;protein-binding site;reporter gene;resource competition;retroactivity;Synthetic biology;systems biology
WOS:000464133600001
Tokyo Inst Technol, Kanagawa, Japan;Waseda Univ, Tokyo, Japan
Japan
2,019
null
0000-0003-1444-5054;0000-0003-3778-5887
null
null
English
null
ACS SYNTH BIOL;AM J PHYSIOL-CELL PH;ANAL NONLINEAR CONTR;APPL ENVIRON MICROB;BIOPHYS J;BIOTECHNIQUES;BMC GENOMICS;BMC SYST BIOL;CELL;COMPUT CHEM ENG;FRONT BIOENG BIOTECH;GENE;IMAGEJ;J Biol Eng;J PHYS CHEM-US;J R SOC INTERFACE;METHOD ENZYMOL;MOL CELL BIOL;MOL SYST BIOL;NAT COMMUN;NAT METHODS;NATURE;NUCLEIC ACIDS RES;P AMER CONTR CONF;P NATL ACAD SCI USA;PHYS REV E;PHYS REV LETT;PLOS BIOL;PLOS COMPUT BIOL;PLOS ONE;SCIENCE
Ayukawa, Shotaro;Kiga, Daisuke;Moriya, Takefumi;Wakao, Shinji;Wakayama, Yuki;Yamamura, Masayuki;Yamaoka, Tomohiro;Zhang, Zicong
2024-03-11 ER
Ayukawa, S;Beal, J;Brewster, R C;Burger, A;Chalfie, M;Chen, Y J;Cookson, N A;Del Vecchio, D;Elowitz, M B;Franco, E;Gardner, T S;Gillespie, D T;Gorman, C M;Graham D.;Gyorgy, A;Hasty, J;Hsu, C;Ishimatsu, K;Jayanthi, S;Kim Kyung, H;Kim, K H;Kumar, N S;Le, T T;Lee, S K;Lee, T H;Lutz, R;Mather, W H;Meijering, E;Miyada, C G;Montminy, M R;Moriya, T;Nordeen, S K;Page, K M;Potvin-Trottier, L;Prindle, A;Rasband, W;Rondelez, Y;Saez-Rodriguez, J;Schneider, C A;Sekine, R;Selden, R F;Shetty Reshma, P;Smolen, P;Stricker, J;Tyler J.;Vanzi, F;Wallace, R G;Wong, O K
HS8QG
Kanagawa, Japan.;Tokyo, Japan
4
null
2
null
30,917,535
Ayukawa, Shotaro;Kiga, Daisuke;Moriya, Takefumi;Wakao, Shinji;Wakayama, Yuki;Yamamura, Masayuki;Yamaoka, Tomohiro;Zhang, Zicong
LIFE-BASEL
Kanagawa, Japan;Tokyo, Japan
Bagh, S;Bonnerjee, D;Mukhopadhyay, S;Sarkar, K;Srivastava, R
10.1186/s13036-019-0151-x
20
CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
543d674h5q474s611e6v1o4as1p2a3c3a5e15
A frame-shifted gene, which rescued its function by non-natural start codons and its application in constructing synthetic gene circuits
Saha Inst Nucl Phys
null
Bagh, S (corresponding author), Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India.
null
Bagh, Sangram;Bonnerjee, Deepro;Mukhopadhyay, Sayak;Sarkar, Kathakali;Srivastava, Rajkamal
Biochemical Research Methods;Biotechnology & Applied Microbiology
IBOP Project, Department of Atomic Energy, Govt. of India; Ramanujan Fellowship of SB, Department of Science and Technology, Govt. of India
WOS
Bagh, S
Saha Inst Nucl Phys, Kolkata, India
13
,;a;and;application;by;circuits;codons;constructing;frame-shifted;function;gene;in;its;non-natural;rescued;start;synthetic;which
1
Bagh, Sangram;Bonnerjee, Deepro;mukhopadhyay, sayak;Sarkar, Kathakali
BMC
Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India
Article
Saha Inst Nucl Phys
LONDON
null
null
Saha Inst Nucl Phys
IBOP Project, Department of Atomic Energy, Govt. of India;Ramanujan Fellowship of SB, Department of Science and Technology, Govt. of India
Bagh, S (corresponding author), Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India.
null
Bagh, Sangram;Bonnerjee, Deepro;Mukhopadhyay, Sayak;Sarkar, Kathakali;Srivastava, Rajkamal
9
1
460,080,300,001
IBOP Project, Department of Atomic Energy, Govt. of India;Ramanujan Fellowship of SB, Department of Science and Technology, Govt. of India
India
JOURNAL OF BIOLOGICAL ENGINEERING
India
null
null
Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India
1754-1611
Bagh, S;Bonnerjee, D;Mukhopadhyay, S;Sarkar, K;Srivastava, R
MAR 1
sangram.bagh@saha.ac.in
application;frame-shifted gene;function;non-natural start codons;synthetic gene circuits
5
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
-repressor cI;3rd codon;application;backgroundFrame-shifted genes resultsin non-functional peptides;BIOLOGY APPLICATIONS;building;building synthetic gene circuits;cI;cI genes;complete loss;demonstrated synthetic genetic NAND;different codon;directed evolution;E coli;effective functionality;Escherichia coli;ESCHERICHIA-COLI;excellent candidate;first report;first several amino acids;frame-shifted cI;Frame-shifted gene;frame-shifted gene.ConclusionsThis study;frame-shifted geneshavenever;function;functional;functions;Gate;gates;Gene circuits;genetic NOT-gates;growth;high regulatory ranges (>300);Hill coefficient (>6.5);large range;library;mutation;new operating mechanism;new view;non-directed evolution;Non-directed evolution of synthetic gene circuit;non-functional synthetic gene circuit;non-natural start codon;Non-natural start codons;NOR logic-gates;novel way;one form;properties;relative copy numbers;Rescued function;serve;SIGNIFICANCE;similar repression behavior;single nucleotide deletion mutation;start codon ACA;starting;starts;synthetic;synthetic gene circuits;synthetic gene circuits.ResultsHere;synthetic genetic circuits;synthetic-gene-circuits;target promoter;translatingfrom;TRANSLATION INITIATION;understanding;whole frame-shifted gene
Sarkar, K
BIOLOGY APPLICATIONS;directed evolution;E coli;ESCHERICHIA-COLI;Frame-shifted gene;Non-directed evolution of synthetic gene circuit;Non-natural start codons;Rescued function;synthetic gene circuits;TRANSLATION INITIATION
null
[Sarkar, Kathakali; Mukhopadhyay, Sayak; Bonnerjee, Deepro; Srivastava, Rajkamal; Bagh, Sangram] Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India.
This work was supported by IBOP Project, Department of Atomic Energy, Govt. of India and Ramanujan Fellowship of SB, Department of Science and Technology, Govt. of India.
-repressor cI;3rd codon;backgroundFrame-shifted genes resultsin non-functional peptides;building;building synthetic gene circuits;cI;cI genes;complete loss;demonstrated synthetic genetic NAND;different codon;effective functionality;Escherichia coli;excellent candidate;first report;first several amino acids;frame-shifted cI;frame-shifted gene;frame-shifted gene.ConclusionsThis study;frame-shifted geneshavenever;function;functional;functions;gate;gates;gene circuits;genetic NOT-gates;growth;high regulatory ranges (>300);Hill coefficient (>6.5);large range;library;mutation;new operating mechanism;new view;non-directed evolution;non-functional synthetic gene circuit;non-natural start codon;NOR logic-gates;novel way;one form;properties;relative copy numbers;serve;SIGNIFICANCE;similar repression behavior;single nucleotide deletion mutation;start codon ACA;starting;starts;synthetic;synthetic gene circuits.ResultsHere;synthetic genetic circuits;synthetic-gene-circuits;target promoter;translatingfrom;understanding;whole frame-shifted gene
10.1002/anie.201708408;10.1002/bit.22969;10.1007/BF00352506;10.1016/j.copbio.2016.03.016;10.1016/j.synbio.2017.09.003;10.1021/sb4000564;10.1038/nbt.1568;10.1038/nbt.2714;10.1038/nchembio.1411;10.1038/nrg2775;10.1038/srep29574;10.1073/pnas.252535999;10.1093/nar/22.23.4953;10.1093/nar/25.6.1203;10.1093/nar/gkt1139;10.1093/nar/gkx070;10.1093/nar/gkx472;10.1099/mic.0.067975-0;10.1103/PhysRevE.77.021919;10.1103/PhysRevE.82.021911;10.1128/AEM.01684-08;10.15252/msb.20145735;10.15252/msb.20167265;[10.1038/NMETH.2926, 10.1038/nmeth.2926]
Saha Inst Nucl Phys
Bagh, S;Bonnerjee, D;Mukhopadhyay, S;Sarkar, K;Srivastava, R
Sarkar, K: Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India
mukhopadhyay, sayak
null
25
null
India
Saha Inst Nucl Phys
Sarkar, Kathakali
Green Published, gold
BIOLOGY APPLICATIONS;DIRECTED EVOLUTION;ESCHERICHIA-COLI;TRANSLATION INITIATION
Sarkar, Kathakali; Mukhopadhyay, Sayak; Bonnerjee, Deepro; Srivastava, Rajkamal; Bagh, Sangram;
null
Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India
Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India
null
E. coli;Frame-shifted gene;Non-directed evolution of synthetic gene circuit;Non-natural start codons;Rescued function;Synthetic gene circuit
null
1981;1994;1997;2002;2004;2008;2009;2010;2011;2013;2014;2016;2017;2018
5
Saha Inst Nucl Phys, Homi Bhabha Natl Inst, Biophys & Struct Genom Div, Block A-F,Sect 1, Kolkata 700064, India
J. Biol. Eng.
Bagh, Sangram
BMC
(>300);(>6.5);,;-repressor;3rd;a;ACA;acids;also;amino;among;an;and;as;backgroundFrame-shifted;became;because;been;behavior;between;building;by;candidate;cI;circuit;circuits;circuits.ResultsHere;codon;coefficient;coli;complete;constructing;copy;deletion;demonstrated;developed;different;during;each;effective;engineered;Escherichia;evidence;evolution;excellent;first;for;form;found;frame-shifted;from;function;functional;functionality;functions;gate;gates;gene;gene.ConclusionsThis;genes;geneshavenever;genetic;growth;had;have;high;Hill;hypothesized;in;inspires;is;it;its;large;library;logic-gates;loss;made;make;may;mechanism;mutation;NAND;new;non-directed;non-functional;non-natural;NOR;not;NOT-gates;novel;nucleotide;numbers;of;on;one;operating;optimizing;over;peptides;promoter;properties;range;ranges;regulatory;relative;report;repression;rescued;resulted;resultsin;series;serve;several;showed;SIGNIFICANCE;similar;single;start;starting;starts;study;synthetic;synthetic-gene-circuits;target;tested;that;the;these;this;through;translated;translatingfrom;understanding;used;view;was;way;we;which;whole;with;within;work;worked
Saha Inst Nucl Phys
BackgroundFrame-shifted genes resultsin non-functional peptides. Because of this complete loss of function, frame-shifted geneshavenever been used in constructing synthetic gene circuits.ResultsHere we report that the function of gene circuits is rescued by a frame-shifted gene, which functions by translatingfrom a non-natural start codon. We report a single nucleotide deletion mutation that developed in the -repressor cI within a synthetic genetic NOT gate in Escherichia coli during growth and through this mutation, a non-functional synthetic gene circuit became functional. This mutation resulted in a frame-shifted cI, which showed effective functionality among genetic NOT-gates in Escherichia coli with high regulatory ranges (>300) and Hill coefficient (>6.5). The cI worked over a large range of relative copy numbers between the frame-shifted gene and its target promoter. These properties make this frame-shifted gene an excellent candidate for building synthetic gene circuits. We hypothesized a new operating mechanism and showed evidence that frame-shifted cI was translated from non-natural start codon. We have engineered and tested a series of NOT gates made from a library of cI genes, each of which starts from a different codon within the first several amino acids of the frame-shifted cI. It is found that one form with start codon ACA, starting from the 3rd codon had similar repression behavior as the whole frame-shifted gene. We demonstrated synthetic genetic NAND and NOR logic-gates with frame-shifted cI. This is the first report of synthetic-gene-circuits made from a frame-shifted gene.ConclusionsThis study inspires a new view on frame-shifted gene and may serve as a novel way of building and optimizing synthetic-gene-circuits. This work may also have significance in the understanding of non-directed evolution of synthetic genetic circuits.
HJI-3440-2023
BIOLOGY APPLICATIONS;DIRECTED EVOLUTION;ESCHERICHIA-COLI;TRANSLATION INITIATION
0
null
E coli;Frame-shifted gene;Non-directed evolution of synthetic gene circuit;Non-natural start codons;Rescued function;synthetic gene circuits
10
E. coli;ESCHERICHIA-COLI;BIOLOGY APPLICATIONS;directed evolution;Frame-shifted gene;Non-directed evolution of synthetic gene circuit;Non-natural start codons;Rescued function;synthetic gene circuits;TRANSLATION INITIATION
WOS:000460080300001
Saha Inst Nucl Phys, Kolkata, India
India
2,019
null
0000-0002-2172-6893;0000-0002-5736-0993;0000-0002-6531-2254;0000-0002-8565-0728
null
null
English
null
A Genetic Switch;ACS SYNTH BIOL;Angew Chem Int Ed Engl;APPL ENVIRON MICROB;BIOTECHNOL BIOENG;CURR OPIN BIOTECH;MICROBIOL-SGM;MOL GEN GENET;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT METHODS;NAT REV GENET;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV E;SCI REP-UK;SYN SYST BIOTECHNO
Bagh, Sangram;Bonnerjee, Deepro;Mukhopadhyay, Sayak;Sarkar, Kathakali;Srivastava, Rajkamal
2024-03-11 ER
Ang, J;Arnold Frances, H;Arpino, J A J;Bagh, S;Bassalo, M C;Borujeni, A E;Brophy, J A N;Chen, H Y;Ellefson, J W;Engstrom, M D;He, C G;Hecht, A;Khalil, A S;Lieb, M;Lutz, R;Nielsen, A A;Ptashne M.;Rasmussen, K K;Salis, H M;Sayut, D J;Schreiber, J;Stanton, B C;Yokobayashi, Y
HN3JT
Kolkata, India
5
null
1
null
30,867,677
Bagh, Sangram;Bonnerjee, Deepro;Mukhopadhyay, Sayak;Sarkar, Kathakali;Srivastava, Rajkamal
J BIOL ENG
Kolkata, India
Cai, Z M;Ding, M T;Fang, L;Gao, Q J;Huang, W R;Liao, X H;Liu, Y C;Liu, Y H;Xie, H B A;Yang, K;Zhan, H J;Zhou, Q
10.1111/cpr.12552
e12552
111 RIVER ST, HOBOKEN 07030-5774, NJ USA
555l7256s1341e5r3p35616y4rdk3s6mq57
A revolutionary tool: CRISPR technology plays an important role in construction of intelligentized gene circuits
Anhui Med Univ
null
Cai, ZM; Huang, WR; Liu, YC (corresponding author), Shenzhen Univ, Affiliated Hosp 1, Dept Urol, Shenzhen, Guangdong, Peoples R China.
null
Cai, Zhiming;Ding, Mengting;Fang, Lan;Gao, Qunjun;Huang, Weiren;Liao, Xinhui;Liu, Yuchen;Liu, Yuhan;Xie, Haibiao;Yang, Kang;Zhan, Hengji;Zhou, Qun
Cell Biology
National Natural Science Foundation of China [81772737]; Guangdong Provincial Department of Science and Technology [2017A020215120]; High Level University's Medical Discipline Construction project [2016031638]; Shenzhen Municipal Government of China [JCYJ20170413161749433, JSGG20160301161836370]; National Key Basic Research Program of China (973 Program) [2014CB745201]; Sanming Project of Shenzhen Health and Family Planning Commission [SZSM201412018, SZSM201512037]
WOS
Cai, Z M;Huang, W R;Liu, Y C
Anhui Med Univ, Shenzhen, Peoples R China;Shenzhen Univ, Guangdong, Peoples R China
52
:;a;an;circuits;construction;CRISPR;gene;important;in;intelligentized;of;plays;revolutionary;role;technology;tool
1
ding, mengting;Gao, Qunjun;Liu, Haibo;Liu, Yuchen;Liu, Yuhan;Liu, Yujie;Wang, Hao
WILEY
Anhui Med Univ, Dept Urol, Shenzhen Peoples Hosp 2, Clin Med Coll, Shenzhen, Peoples R China;Shenzhen Univ, Affiliated Hosp 1, Dept Urol, Shenzhen, Guangdong, Peoples R China;WR; Liu, YC (corresponding author), Shenzhen Univ, Affiliated Hosp 1, Dept Urol, Shenzhen, Guangdong, Peoples R China
Review
Shenzhen Univ
HOBOKEN
null
null
Anhui Med Univ;Shenzhen Univ
Guangdong Provincial Department of Science and Technology;High Level University's Medical Discipline Construction project;National Key Basic Research Program of China (973 Program);National Natural Science Foundation of China;Sanming Project of Shenzhen Health and Family Planning Commission;Shenzhen Municipal Government of China
Cai, ZM; Huang, WR; Liu, YC (corresponding author), Shenzhen Univ, Affiliated Hosp 1, Dept Urol, Shenzhen, Guangdong, Peoples R China.
null
Cai, Zhiming;Ding, Mengting;Fang, Lan;Gao, Qunjun;Huang, Weiren;Liao, Xinhui;Liu, Yuchen;Liu, Yuhan;Xie, Haibiao;Yang, Kang;Zhan, Hengji;Zhou, Qun
30
2
463,046,500,003
Guangdong Provincial Department of Science and Technology [2017A020215120];High Level University's Medical Discipline Construction project [2016031638];National Key Basic Research Program of China (973 Program) [2014CB745201];National Natural Science Foundation of China [81772737];Sanming Project of Shenzhen Health and Family Planning Commission [SZSM201412018, SZSM201512037];Shenzhen Municipal Government of China [JCYJ20170413161749433, JSGG20160301161836370]
China
CELL PROLIFERATION
China
null
null
Anhui Med Univ, Dept Urol, Shenzhen Peoples Hosp 2, Clin Med Coll, Shenzhen, Peoples R China
0960-7722
Cai, Z M;Ding, M T;Fang, L;Gao, Q J;Huang, W R;Liao, X H;Liu, Y C;Liu, Y H;Xie, H B A;Yang, K;Zhan, H J;Zhou, Q
MAR
caizhiming2000@163.com;liuyuchenmdcg@163.com;pony8980@163.com
CRISPR technology;important role;intelligentized gene circuits;revolutionary tool
12
J
Cell Biology
activation;application;artificial;artificial switch-inducible Cas9;BIOLOGY;cancer therapy;Cas9;commodity chemicals;complex;CRISPR system;CRISPR technology;CRISPR-associated RNA-guided endonuclease Cas9 (CRISPR-associated protein 9)-targeted genome editing tool;CRISPR-based gene circuit development;CRISPR/Cas systems;CRYSTAL-STRUCTURE;development;efficiency;engineering gene circuits;Gene circuits;gene editing;gene therapy;great applied potential;high efficiency;IDENTIFICATION;important role;integration;intelligentized;intelligentized gene circuits;interspaced short palindromic repeat (CRISPR) system;lack;medicine;networks;new way;normal cells;poor anti-tumour effects;precision cancer therapy;programmability;programmable;prospectives;recent advances;REPRESSION;revolutionary tool;RNA;safety;sequence-specific gene editing tools;single targets;specificity;synthetic biology;synthetic gene circuits;target;traditional single-targeted therapy;TRANSCRIPTIONAL CONTROL;treat tumour cells;tumour cells;tumour-specific targets;ultimate challenge;underlying challenges;unique properties-operability;use
Zhou, Q
ACTIVATION;artificial;CAS9;COMPLEX;CRISPR technology;CRYSTAL-STRUCTURE;Gene circuits;gene editing;IDENTIFICATION;INTEGRATION;intelligentized;NETWORKS;REPRESSION;RNA;TRANSCRIPTIONAL CONTROL
null
[Zhou, Qun; Fang, Lan; Ding, Mengting; Cai, Zhiming; Huang, Weiren] Anhui Med Univ, Dept Urol, Shenzhen Peoples Hosp 2, Clin Med Coll, Shenzhen, Peoples R China. [Zhou, Qun; Zhan, Hengji; Liao, Xinhui; Liu, Yuhan; Xie, Haibiao; Yang, Kang; Gao, Qunjun; Ding, Mengting; Cai, Zhiming; Huang, Weiren; Liu, Yuchen] Shenzhen Univ, Affiliated Hosp 1, Dept Urol, Shenzhen, Guangdong, Peoples R China.
the National Natural Science Foundation of China, Grant/Award Number: 81772737; Guangdong Provincial Department of Science and Technology, Grant/Award Number: 2017A020215120; the High Level University's Medical Discipline Construction project, Grant/Award Number: 2016031638; the Shenzhen Municipal Government of China, Grant/Award Number: JCYJ20170413161749433 and JSGG20160301161836370; the National Key Basic Research Program of China (973 Program), Grant/Award Number: 2014CB745201; the Sanming Project of Shenzhen Health and Family Planning Commission, Grant/Award Number: SZSM201412018 and SZSM201512037
application;artificial switch-inducible Cas9;biology;cancer therapy;commodity chemicals;CRISPR system;CRISPR technology;CRISPR-associated RNA-guided endonuclease Cas9 (CRISPR-associated protein 9)-targeted genome editing tool;CRISPR-based gene circuit development;CRISPR/Cas systems;development;efficiency;engineering gene circuits;gene circuits;gene therapy;great applied potential;high efficiency;intelligentized gene circuits;interspaced short palindromic repeat (CRISPR) system;lack;medicine;new way;normal cells;poor anti-tumour effects;precision cancer therapy;programmability;programmable;prospectives;recent advances;safety;sequence-specific gene editing tools;single targets;specificity;synthetic biology;synthetic gene circuits;target;traditional single-targeted therapy;treat tumour cells;tumour cells;tumour-specific targets;ultimate challenge;underlying challenges;unique properties-operability;use
10.1002/hep.30084;10.1016/j.cell.2013.02.022;10.1016/j.cell.2013.06.044;10.1016/j.cell.2014.02.001;10.1016/j.cell.2014.09.029;10.1016/j.cell.2014.11.052;10.1016/j.cell.2015.08.007;10.1016/j.cell.2016.01.012;10.1016/j.cell.2016.02.004;10.1016/j.cell.2017.07.037;10.1016/j.cell.2017.09.049;10.1016/j.chembiol.2014.12.011;10.1016/j.molcel.2014.04.022;10.1016/j.molcel.2015.10.008;10.1016/j.tibtech.2015.12.014;10.1016/j.ymeth.2014.06.014;10.1016/S0092-8674(00)81683-9;10.1016/S1470-2045(09)70240-2;10.1021/acschembio.7b00603;10.1021/acssynbio.7b00425;10.1021/acssynbio.8b00202;10.1021/sb4000417;10.1021/sb4001867;10.1038/cr.2013.122;10.1038/msb.2010.99;10.1038/nature08753;10.1038/nature10886;10.1038/nature11245;10.1038/nature12148;10.1038/nature13011;10.1038/nature14299;10.1038/nature14571;10.1038/nature15544;10.1038/nature16526;10.1038/nature21059;10.1038/nature24268;10.1038/nbt.2808;10.1038/nbt.3199;10.1038/nchembio.1736;10.1038/ncomms13056;10.1038/ncomms3825;10.1038/ncomms4728;10.1038/ncomms5408;10.1038/ncomms6393;10.1038/nprot.2018.007;10.1038/nrmicro3569;10.1038/s41467-017-02075-1;10.1038/s41467-017-02265-x;10.1038/s41467-018-03475-7;10.1073/pnas.1620299114;10.1089/hum.2017.172;10.1105/tpc.15.00852;10.1111/pbi.12981;10.1126/sciadv.1701620;10.1126/science.1172005;10.1126/science.1192128;10.1126/science.1205527;10.1126/science.1207084;10.1126/science.1256272;10.1126/science.aan4672;10.3748/wjg.v22.i3.1179;10.7150/ijbs.16162;10.7554/eLife.31936;[10.1038/nmeth.2184, 10.1038/NMETH.2184];[10.1038/NMETH.2681, 10.1038/nmeth.2681];[10.1038/NMETH.2926, 10.1038/nmeth.2926];[10.1038/NMETH.2969, 10.1038/nmeth.2969];[10.1038/NMETH.3312, 10.1038/nmeth.3312];[10.1038/NMETH.3580, 10.1038/nmeth.3580];[10.1038/NMETH.3994, 10.1038/nmeth.3994]
Anhui Med Univ
Cai, Z M;Ding, M T;Fang, L;Gao, Q J;Huang, W R;Liao, X H;Liu, Y C;Liu, Y H;Xie, H B A;Yang, K;Zhan, H J;Zhou, Q
Zhou, Q: Anhui Med Univ, Dept Urol, Shenzhen Peoples Hosp 2, Clin Med Coll, Shenzhen, Peoples R China
ding, mengting;fang, yu;guo, ppdop;LI, Wenhui;li, xiaofeng;Liu, Haibo;liu, xiao;LIU, YU;liu, yuchen;Liu, Yujie;lu, yang;wang, hang;Wang, Hao;wang, jiajun;Wang, Luyao;wang, xiaoqiang;wang, ya;wang, yi;zhan, xiao;ZHAO, S;zhou, wei;zhou, yang
2014CB745201;2016031638;2017A020215120;81772737;JCYJ20170413161749433;JSGG20160301161836370;SZSM201412018;SZSM201512037
70
null
China
Anhui Med Univ;Shenzhen Univ
Zhou, Qun
hybrid, Green Published
ACTIVATION;CAS9;COMPLEX;CRYSTAL-STRUCTURE;IDENTIFICATION;INTEGRATION;NETWORKS;REPRESSION;RNA;TRANSCRIPTIONAL CONTROL
Zhou, Qun; Zhan, Hengji; Liao, Xinhui; Fang, Lan; Liu, Yuhan; Xie, Haibiao; Yang, Kang; Gao, Qunjun; Ding, Mengting; Cai, Zhiming; Huang, Weiren; Liu, Yuchen;
null
Anhui Med Univ, Dept Urol, Shenzhen Peoples Hosp 2, Clin Med Coll, Shenzhen, Peoples R China;Shenzhen Univ, Affiliated Hosp 1, Dept Urol, Shenzhen, Guangdong, Peoples R China
Anhui Med Univ, Dept Urol, Shenzhen Peoples Hosp 2, Clin Med Coll, Shenzhen, Peoples R China;Shenzhen Univ, Affiliated Hosp 1, Dept Urol, Shenzhen, Guangdong, Peoples R China
1365-2184
artificial;CRISPR technology;Gene circuits;gene editing;intelligentized
2
2000;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018;2019
5
Shenzhen Univ, Affiliated Hosp 1, Dept Urol, Shenzhen, Guangdong, Peoples R China
Cell Prolif.
Liu, Yuchen
WILEY
(CRISPR);(CRISPR-associated;,;9)-targeted;a;advances;also;an;and;anti-tumour;application;applied;artificial;as;assessed;based;be;been;biology;cancer;cannot;Cas9;cells;challenge;challenges;chemicals;circuit;circuits;clustered;commodity;construction;could;CRISPR;CRISPR-associated;CRISPR-based;CRISPR/Cas;currently;design;development;discussed;distinguish;editing;effective;effectively;effects;efficiency;endonuclease;engineering;especially;for;from;gene;genome;great;guarantees;has;have;hence;here;high;if;in;intelligentized;interspaced;is;its;lack;limits;medicine;more;moreover;new;normal;of;on;palindromic;poor;potential;precision;programmability;programmable;properties-operability;prospectives;protein;provides;recent;recently;regularly;repeat;RNA-guided;safety;secure;sequence-specific;severely;short;shown;single;single-targeted;specificity;switch-inducible;synthetic;system;systems;target;targets;technology;the;therapy;to;tool;tools;traditional;treat;tumour;tumour-specific;ultimate;underlying;unique;use;used;using;way;we;which;with
Shenzhen Univ
With the development of synthetic biology, synthetic gene circuits have shown great applied potential in medicine, biology, and as commodity chemicals. An ultimate challenge in the construction of gene circuits is the lack of effective, programmable, secure and sequence-specific gene editing tools. The clustered regularly interspaced short palindromic repeat (CRISPR) system, a CRISPR-associated RNA-guided endonuclease Cas9 (CRISPR-associated protein 9)-targeted genome editing tool, has recently been applied in engineering gene circuits for its unique properties-operability, high efficiency and programmability. The traditional single-targeted therapy cannot effectively distinguish tumour cells from normal cells, and gene therapy for single targets has poor anti-tumour effects, which severely limits the application of gene therapy. Currently, the design of gene circuits using tumour-specific targets based on CRISPR/Cas systems provides a new way for precision cancer therapy. Hence, the application of intelligentized gene circuits based on CRISPR technology effectively guarantees the safety, efficiency and specificity of cancer therapy. Here, we assessed the use of synthetic gene circuits and if the CRISPR system could be used, especially artificial switch-inducible Cas9, to more effectively target and treat tumour cells. Moreover, we also discussed recent advances, prospectives and underlying challenges in CRISPR-based gene circuit development.
ABB-8923-2020;GQI-4698-2022;GXF-9442-2022;GYQ-6286-2022;HMD-7454-2023;HOF-6668-2023;HQZ-7558-2023;HTR-1607-2023;IWE-3635-2023;IWU-6535-2023;IWV-4219-2023;JCD-9947-2023;JED-3951-2023;JEZ-3810-2023;JLL-2001-2023;JMT-2783-2023;JND-8481-2023;JQJ-0490-2023;JRW-6032-2023;JWP-8549-2024;KAL-9865-2024;KCK-2014-2024
ACTIVATION;CAS9;COMPLEX;TRANSCRIPTION CONTROL;CRYSTAL-STRUCTURE;IDENTIFICATION;INTEGRATION;NETWORKS;REPRESSION;RNA
2
null
artificial;CRISPR technology;Gene circuits;gene editing;intelligentized
8
ACTIVATION;artificial;CAS9;COMPLEX;TRANSCRIPTION CONTROL;CRISPR technology;CRYSTAL-STRUCTURE;Gene circuits;gene editing;IDENTIFICATION;INTEGRATION;intelligentized;NETWORKS;REPRESSION;RNA
WOS:000463046500003
Anhui Med Univ, Shenzhen, Peoples R China;Shenzhen Univ, Guangdong, Peoples R China
China
2,019
null
0000-0001-9109-6017;0000-0001-9156-0457;0000-0002-1153-6156;0000-0002-4213-2883;0000-0002-6517-0022;0000-0002-6524-1230;0000-0003-1990-4184
null
null
English
null
ACS CHEM BIOL;ACS SYNTH BIOL;CELL;CELL RES;CHEM BIOL;ELIFE;HEPATOLOGY;HUM GENE THER;INT J BIOL SCI;LANCET ONCOL;METHODS;MOL CELL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT PROTOC;NAT REV MICROBIOL;NATURE;P NATL ACAD SCI USA;PLANT BIOTECHNOL J;PLANT CELL;SCI ADV;SCIENCE;TRENDS BIOTECHNOL;WORLD J GASTROENTERO
Cai, Zhiming;Ding, Mengting;Fang, Lan;Gao, Qunjun;Huang, Weiren;Liao, Xinhui;Liu, Yuchen;Liu, Yuhan;Xie, Haibiao;Yang, Kang;Zhan, Hengji;Zhou, Qun
2024-03-11 ER
Ausländer, D;Biarnes-Carrera, M;Brophy, J A N;Burstein, D;Charpentier, M;Chavez, A;Chen, J S;Cheng, A W;Choi, P S;Culler, S J;Daniel, R;Danino, T;Dunbar, C E;Esvelt, K M;Farzadfard, F;Friedland, A E;Fu, Y F;Gerstein, M B;Gilbert, L A;Grimm, D;Gupta, S;Hanahan, D;Harrington, L B;Hilton, I B;Howden, S E;Jansing, J;Jusiak, B;Kabadi, A M;Kiani, S;Kipniss, N H;Kleinstiver, B P;Lee, S Y;Lenis, T L;Li, Y Q;Lin, F;Liu, C C;Liu, Y C;Ma, D C;Maddalo, D;Makarova, K S;Megraw, M;Morsut, L;Nandagopal, N;Nielsen, J;Nihongaki, Y;Nishimasu, H;Nissim, L;Preziosi, M;Qi, L S;Ran, F A;Rini, B I;Rössger, K;Shin, J;Shmakov, S;Sternberg, S H;Strovas, T J;Wiedenheft, B;Xie, Z;Zalatan, J G;Zhan, H J;Zhou, X X
HR3NW
Guangdong, Peoples R China
7
null
2
null
30,520,167
Cai, Zhiming;Ding, Mengting;Fang, Lan;Gao, Qunjun;Huang, Weiren;Liao, Xinhui;Liu, Yuchen;Liu, Yuhan;Xie, Haibiao;Yang, Kang;Zhan, Hengji;Zhou, Qun
CELL PROLIFERAT
Guangdong, Peoples R China;Shenzhen, Peoples R China
Gupta, A;Zou, J
10.1038/s42256-019-0017-4
null
HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
37181d4ce3h3yj1260573s6d3w416t583y3m5g
Feedback GAN for DNA optimizes protein functions
Stanford Univ
null
Zou, J (corresponding author), Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA.;Zou, J (corresponding author), Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
null
Gupta, Anvita;Zou, James
Computer Science, Artificial Intelligence;Computer Science, Interdisciplinary Applications
Chan-Zuckerberg Biohub Investigator grant; National Science Foundation (NSF) grant [CRII 1657155]
WOS
Zou, J
Stanford Univ, Stanford, CA USA
1
DNA;feedback;for;functions;GAN;optimizes;protein
1
null
NATURE PORTFOLIO
Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA;Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA;Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.; Zou, J (corresponding author), Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA
Article
Stanford Univ
BERLIN
null
null
Stanford Univ
Chan-Zuckerberg Biohub Investigator grant;National Science Foundation (NSF) grant
Zou, J (corresponding author), Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.; Zou, J (corresponding author), Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA.
111
Gupta, Anvita;Zou, James
52
2
567,066,600,008
Chan-Zuckerberg Biohub Investigator grant;National Science Foundation (NSF) grant [CRII 1657155]
USA
NATURE MACHINE INTELLIGENCE
USA;USA.;
null
null
Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
null
Gupta, A;Zou, J
FEB
jamesz@stanford.edu
DNA;feedback GAN;protein functions
2
J
Computer Science
advantage;analyser;antimicrobial peptides;applications;coding;DATABASE;desirable biophysical properties;desired properties;differentiable;DNA;DNA sequences;domains;drug discovery;drugs;environmental treatment;external function analyser;FBGAN architecture;feedback GAN;feedback GAN (FBGAN);feedback-loop architecture;feedback-loop mechanism;GAN-generated data points;GAN-generated proteins;GANs;generative adversarial;generative adversarial networks (GANs);generative machine learning models;genes;genomics;gupta;macromolecules;manufacturing;metrics;new structures;novel approach;novel feedback-loop architecture;ones;output;proposed architecture;protein functions;proteins;realistic data;resulting peptides;secondary structure;silico;suite;synthetic biology;synthetic DNA sequences encoding;synthetic gene sequences;synthetic genes;synthetic genes coding;two examples;useful properties;variable length;Zou
Gupta, A
DATABASE
105
[Gupta, Anvita; Zou, James] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. [Zou, James] Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA.
The authors thank A. Kundaje for guidance when initiating the research on GANs and DNA. J.Z. is supported by a Chan-Zuckerberg Biohub Investigator grant and National Science Foundation (NSF) grant CRII 1657155.
advantage;analyser;antimicrobial peptides;applications;coding;desirable biophysical properties;desired properties;differentiable;DNA sequences;domains;drug discovery;drugs;environmental treatment;external function analyser;FBGAN architecture;feedback GAN (FBGAN);feedback-loop architecture;feedback-loop mechanism;GAN-generated data points;GAN-generated proteins;GANs;generative adversarial;generative adversarial networks (GANs);generative machine learning models;genes;genomics;gupta;macromolecules;manufacturing;metrics;new structures;novel approach;novel feedback-loop architecture;ones;output;proposed architecture;proteins;realistic data;resulting peptides;secondary structure;silico;suite;synthetic biology;synthetic DNA sequences encoding;synthetic gene sequences;synthetic genes;synthetic genes coding;two examples;useful properties;variable length;Zou
10.1002/minf.201700111;10.1002/prot.24065;10.1016/j.jaad.2004.08.026;10.1016/S0734-9750(03)00077-6;10.1021/acs.jcim.7b00414;10.1021/acscentsci.7b00512;10.1038/nrg1637;10.1093/bioinformatics/btx285;10.1093/nar/gkt381;10.1093/nar/gkv1051;10.1093/nar/gkv1278;10.1101/227645V1;10.1101/262501V2];10.1126/science.aan0693;10.1145/3422622;10.1186/s13321-017-0235-x;10.1371/journal.pcbi.1005242;[10.1093/nar/gkh131, 10.1093/nar/gkw1099]
Stanford Univ
Gupta, A;Zou, J
Gupta, A: Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
null
CRII 1657155
26
null
USA
Stanford Univ
Gupta, Anvita
null
DATABASE
Gupta, Anvita; Zou, James;
null
Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA;Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA;Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
2522-5839
null
2
2003;2004;2005;2012;2013;2016;2017;2018;2020
85
Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA;Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
Nat. Mach. Intell.
Zou, James
NATURE PORTFOLIO
(FBGAN);(GANs);,;:;a;advantage;adversarial;also;an;analyser;and;antimicrobial;applications;apply;approach;architecture;are;as;attractive;be;beyond;biology;biophysical;calculated;can;coding;data;demonstrate;demonstrates;desirable;desired;differentiable;discovery;DNA;does;domains;drug;drugs;encoding;environmental;examples;external;FBGAN;feedback;feedback-loop;find;for;function;GAN;GAN-generated;GANs;gene;generate;generates;generating;generative;genes;genomics;gupta;has;have;here;in;learning;length;machine;macromolecules;manufacturing;mechanism;metrics;models;need;network;networks;new;not;novel;of;ones;optimize;optimizing;or;other;output;peptides;points;produce;properties;propose;proposed;proteins;realistic;represent;resulting;secondary;sequences;silico;specifically;structure;structures;such;suite;synthetic;that;the;their;to;treatment;two;used;useful;using;variable;we;with;Zou
Stanford Univ
Generative adversarial networks (GANs) represent an attractive and novel approach to generate realistic data, such as genes, proteins or drugs, in synthetic biology. Here, we apply GANs to generate synthetic DNA sequences encoding for proteins of variable length. We propose a novel feedback-loop architecture, feedback GAN (FBGAN), to optimize the synthetic gene sequences for desired properties using an external function analyser. The proposed architecture also has the advantage that the analyser does not need to be differentiable. We apply the feedback-loop mechanism to two examples: generating synthetic genes coding for antimicrobial peptides, and optimizing synthetic genes for the secondary structure of their resulting peptides. A suite of metrics, calculated in silico, demonstrates that the GAN-generated proteins have desirable biophysical properties. The FBGAN architecture can also be used to optimize GAN-generated data points for useful properties in domains beyond genomics. Generative machine learning models are used in synthetic biology to find new structures such as DNA sequences, proteins and other macromolecules with applications in drug discovery, environmental treatment and manufacturing. Gupta and Zou propose and demonstrate in silico a feedback-loop architecture to optimize the output of a generative adversarial network that generates synthetic genes to produce ones specifically coding for antimicrobial peptides.
null
DATABASE
9
null
null
7
DATABASE
WOS:000567066600008
Stanford Univ, Stanford, CA USA
USA
2,019
null
null
null
null
English
null
ABS160603498;ACS CENTRAL SCI;BIOINFORMATICS;BIOTECHNOL ADV;COMMUN ACM;J AM ACAD DERMATOL;J CHEM INF MODEL;J CHEMINFORMATICS;MOL INFORM;NAT REV GENET;NUCLEIC ACIDS RES;PLOS COMPUT BIOL;PR MACH LEARN RES;PREPRINT;PROTEINS;SCIENCE
Gupta, Anvita;Zou, James
2024-03-11 ER
[Anonymous];Abrusán, G;Apweiler, R;Arjovsky, M;Benner, S A;Buchan, D W A;Esteban C.;Ghahramani A.;Goodfellow, I;Gulrajani, I;Gupta A.;Gupta, A;Izadpanah, A;Killoran N.;Müller, A T;Olivecrona, M;Osokin A.;Papagianni, M;Rocklin, G J;Salimans T.;Segler, M H S;Waghu, F H;Wang, G S;Xu, D;Zhu J.
NK9RV
Stanford, CA USA;Stanford, CA USA.
104
null
1
null
null
Gupta, Anvita;Zou, James
NAT MACH INTELL
Stanford, CA USA
Baulcombe, D C;Navarro, F J
10.1021/acssynbio.8b00393
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
23306x204h4jv703o4x4k2f6o1i566zw2t3w4x
miRNA-Mediated Regulation of Synthetic Gene Circuits in the Green Alga <i>Chlamydomonas reinhardtii</i>
Univ Cambridge
null
Baulcombe, DC (corresponding author), Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England.
null
Baulcombe, David C;Navarro, Francisco J
Biochemical Research Methods
OpenPlant from the Biotechnology and Biological Sciences Research Council (BBSRC); Engineering and Physical Sciences Research Council (EPSRC); BBSRC [BB/L014130/1] Funding Source: UKRI
WOS
Baulcombe, D C
Univ Cambridge, Cambridge, England
8
<i>Chlamydomonas;Alga;circuits;gene;Green;in;miRNA-Mediated;of;regulation;reinhardtii</i>;synthetic;the
1
NAVARRO, FRANCISCO J.
AMER CHEMICAL SOC
Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England
Article
Univ Cambridge
WASHINGTON
null
null
Univ Cambridge
BBSRC;Engineering and Physical Sciences Research Council (EPSRC);OpenPlant from the Biotechnology and Biological Sciences Research Council (BBSRC)
Baulcombe, DC (corresponding author), Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England.
370
Baulcombe, David C;Navarro, Francisco J
26
1
459,367,000,018
BBSRC [BB/L014130/1] Funding Source: UKRI;Engineering and Physical Sciences Research Council (EPSRC);OpenPlant from the Biotechnology and Biological Sciences Research Council (BBSRC)
UK
ACS SYNTHETIC BIOLOGY
UK
null
null
Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England
2161-5063
Baulcombe, D C;Navarro, F J
FEB
dcb40@cam.ac.uk
Green Alga <i>Chlamydomonas reinhardtii</i>;miRNA-Mediated Regulation;synthetic gene circuits
2
J
Biochemistry & Molecular Biology
20-24 nts;action;alga;ARTIFICIAL MICRORNAS;characterization;Chlamydomonas reinhardtii;CLEAVAGE;COMPLEMENTARITY;engineering;expression;flexible design;gene expression;gene expression pipeline;gene expression regulation small size;Green Alga <i>Chlamydomonas reinhardtii</i>;IDENTIFICATION;improved traits;late stage;mechanism;microRNAs (miRNAs);miRNA;miRNA decoys;miRNA-mediated gene expression regulation;miRNA-Mediated Regulation;miRNA-responsive 3'UTRs;miRNAs;new applications;progress;PROVIDES;RNA;ROBUSTNESS;role;self-regulatory loops;small RNA molecules;synthetic biology approach;Synthetic gene circuit;synthetic gene circuits;synthetic gene networks;synthetic miRNAs;SYSTEM;target predictability;tools;tools will;unicellular green alga Chlamydomonas reinhardtii;useful tools
Navarro, F J
ARTIFICIAL MICRORNAS;Chlamydomonas reinhardtii;CLEAVAGE;COMPLEMENTARITY;EXPRESSION;gene expression;IDENTIFICATION;MECHANISM;miRNA;PROGRESS;PROVIDES;RNA;Synthetic gene circuit;SYSTEM
358
[Navarro, Francisco J.; Baulcombe, David C.] Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England.
We would like to thank Ralph Bock (Max Planck Institute for Molecular Plant Physiology, Germany) for the UVM11 strain, Alison Smith and Jim Haseloff (University of Cambridge) for reagents and support, and Adrian Valli and Bruno Martins for critical reading of the manuscript. This work was supported by OpenPlant, which receives its funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). D.C.B. is supported as the Royal Society Edward Penley Abraham Research Professor.
20-24 nts;action;alga;characterization;engineering;flexible design;gene expression;gene expression pipeline;gene expression regulation small size;improved traits;late stage;microRNAs (miRNAs);miRNA decoys;miRNA-mediated gene expression regulation;miRNA-responsive 3'UTRs;miRNAs;new applications;robustness;role;self-regulatory loops;small RNA molecules;synthetic biology approach;synthetic gene networks;synthetic miRNAs;target predictability;tools;tools will;unicellular green alga Chlamydomonas reinhardtii;useful tools
10.1002/wdev.223;10.1007/s10529-011-0590-z;10.1007/s11103-015-0425-8;10.1016/B978-0-12-370873-1.00008-3;10.1016/j.bbrc.2003.09.070;10.1016/j.biortech.2014.10.119;10.1016/j.cbpa.2012.05.192;10.1016/j.cell.2009.01.002;10.1016/j.cell.2009.01.035;10.1016/j.cell.2009.01.046;10.1016/j.cell.2017.09.049;10.1016/j.jbiotec.2012.05.010;10.1016/j.molcel.2011.08.023;10.1016/j.omtn.2018.09.009;10.1016/S1097-2765(02)00541-5;10.1021/acssynbio.8b00251;10.1021/sb4001504;10.1038/nature02874;10.1038/nature04785;10.1038/nature05903;10.1038/ncomms3364;10.1038/ng2079;10.1038/nrg1328;10.1038/nrg2504;10.1038/s41477-017-0024-6;10.1038/srep27810;10.1038/srep30620;10.1073/pnas.0506306102;10.1073/pnas.1710597114;10.1073/pnas.2133841100;10.1074/jbc.M111.316729;10.1093/nar/gkq091;10.1093/nar/gkw151;10.1101/gad.1543507;10.1101/gr.199703.115;10.1104/pp.117.2.455;10.1105/tpc.105.039834;10.1105/tpc.111.094144;10.1105/tpc.113.120972;10.1105/tpc.15.00465;10.1105/tpc.9.6.925;10.1111/j.1365-313X.2007.03328.x;10.1111/j.1365-313X.2008.03746.x;10.1111/j.1365-313X.2008.03758.x;10.1111/j.1365-313X.2008.03767.x;10.1111/nph.13532;10.1111/tpj.12354;10.1111/tpj.12606;10.1111/tpj.12781;10.1126/science.1076311;10.1126/science.1143609;10.1126/science.1205527;10.1126/science.aaa1738;10.1146/annurev.arplant.52.1.363;10.1186/1752-0509-6-131;10.1186/gb-2011-12-4-221;10.1261/rna.2414110;10.1261/rna.7135204;10.1371/journal.pone.0003647;10.1371/journal.pone.0016765;10.1371/journal.pone.0021330;[10.1038/NMETH.3100, 10.1038/nmeth.3100]
Univ Cambridge
Baulcombe, D C;Navarro, F J
Navarro, F J: Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England
null
BB/L014130/1
66
null
UK
Univ Cambridge
Navarro, Francisco J
Green Submitted, Green Accepted
ARTIFICIAL MICRORNAS;CLEAVAGE;COMPLEMENTARITY;EXPRESSION;IDENTIFICATION;MECHANISM;PROGRESS;PROVIDES;RNA;SYSTEM
Navarro, Francisco J.; Baulcombe, David C.;
null
Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England
Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England
null
Chlamydomonas reinhardtii;gene expression;miRNA;Synthetic gene circuit
2
1996;1997;1998;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
12
Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England
ACS Synth. Biol.
Baulcombe, David C
AMER CHEMICAL SOC
(miRNAs);,;20-24;3'UTRs;a;action;addition;alga;and;applications;apply;approach;as;at;based;be;biology;build;can;characterization;characterize;Chlamydomonas;decoys;design;engineering;expression;facilitate;features;fine-tuning;flexible;for;gene;green;harnessed;have;improved;in;increase;is;late;loops;make;many;microRNAs;miRNA;miRNA-mediated;miRNA-responsive;miRNAs;molecules;networks;new;nts;of;on;pipeline;predictability;regulation;reinhardtii;RNA;robustness;role;self-regulatory;size;small;stage;such;synthetic;target;that;the;their;them;then;these;this;to;tools;traits;unicellular;used;useful;we;will;work
Univ Cambridge
MicroRNAs (miRNAs), small RNA molecules of 20-24 nts, have many features that make them useful tools for gene expression regulation small size, flexible design, target predictability, and action at a late stage of the gene expression pipeline. In addition, their role in fine-tuning gene expression can be harnessed to increase robustness of synthetic gene networks. In this work, we apply a synthetic biology approach to characterize miRNA-mediated gene expression regulation in the unicellular green alga Chlamydomonas reinhardtii. This characterization is then used to build tools based on miRNAs, such as synthetic miRNAs, miRNA-responsive 3'UTRs, miRNA decoys, and self-regulatory loops. These tools will facilitate the engineering of gene expression for new applications and improved traits in this alga.
null
ARTIFICIAL MICRORNAS;CLEAVAGE;COMPLEMENTARITY;EXPRESSION;IDENTIFICATION;MECHANISM;PROGRESS;PROVIDES;RNA;SYSTEM
3
null
Chlamydomonas reinhardtii;gene expression;miRNA;Synthetic gene circuit
25
ARTIFICIAL MICRORNAS;CHLAMYDOMONAS-REINHARDTII;CLEAVAGE;COMPLEMENTARITY;EXPRESSION;GENE-EXPRESSION;IDENTIFICATION;MECHANISM;miRNA;PROGRESS;PROVIDES;RNA;synthetic gene circuits;SYSTEM
WOS:000459367000018
Univ Cambridge, Cambridge, England
UK
2,019
null
0000-0002-9332-0737
null
null
English
null
ACS SYNTH BIOL;ANNU REV PLANT PHYS;BIOCHEM BIOPH RES CO;BIORESOURCE TECHNOL;BIOTECHNOL BIOFUELS;BIOTECHNOL LETT;BMC SYST BIOL;CELL;CHLAMYDOMONAS SOURCE;CURR OPIN CHEM BIOL;GENE DEV;GENOME BIOL;GENOME RES;J BIOL CHEM;J BIOTECHNOL;MOL CELL;MOL GEN GENET;MOL THER-NUCL ACIDS;NAT COMMUN;NAT GENET;NAT METHODS;NAT PLANTS;NAT REV GENET;NATURE;NEW PHYTOL;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLANT CELL;PLANT CELL PHYSL;PLANT J;PLANT MOL BIOL;PLANT PHYSIOL;PLOS ONE;RNA;SCI REP-UK;SCIENCE;SYNTH BIOL SCOP APPL;WIRES DEV BIOL
Baulcombe, David C;Navarro, Francisco J
2024-03-11 ER
Axtell, M J;Baek, K;Barahimipour, R;Bartel, D P;Baulcombe, D;Benenson, Y;Bloom, R J;Bosia, C;Burgess, S J;Cai, X Z;Carthew, R W;Cerutti, H;Chung, B Y W;Crozet, P;Ebert, M S;Engler, C;Ferenczi, A;Ferrante, P;Franco-Zorrilla, J M;Ghildiyal, M;Harris E.H.;Harris, E H;Hollensen, A K;Hu, J L;Ivashuta, S;Kim, E J;Kitney, R;Li, X B;Liang, J C;Lin, S L;Liu, Q K;Llave, C;Mangan, S;Mckeague, M;Merchant, S S;Molnar, A;Molnár, A;Murphy, K F;Neupert, J;Newman, J R S;Nissim, L;Ossowski, S;Palombella, A L;Patron, N;Reichel, M;Scaife, M A;Schmiedel, J M;Schwab, R;Shin, S E;Siciliano, V;Stegmeier, F;Steinkraus, B R;Stevens, D R;Szczesniak M., W;Valli, A A;Voinnet, O;Wang, C;Weber, E;Xie, Z;Yamasaki, T;Yan, J;Zeng, Y;Zhao, T
HM3IM
Cambridge, England
12
null
1
null
30,624,905
Baulcombe, David C;Navarro, Francisco J
ACS SYNTH BIOL
Cambridge, England
Fukuda, N;Honda, S
10.1016/bs.mie.2019.02.036
null
525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
6e6j1m35l3q15443c466r6d1h6i5a2m5ks2l1m
Synthetic gene expression circuits regulating sexual reproduction
Natl Inst Adv Ind Sci & Technol
Methods in Enzymology
Fukuda, N (corresponding author), Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan.
null
Fukuda, Nobuo;Honda, Shinya
Biochemical Research Methods;Biochemistry & Molecular Biology;Cell Biology
JSPS KAKENHI [25820406, 16K14497, 18K05424]; Grants-in-Aid for Scientific Research [16K14497, 18K05424, 25820406] Funding Source: KAKEN
WOS
Fukuda, N
Natl Inst Adv Ind Sci & Technol, Ibaraki, Japan
621
circuits;expression;gene;regulating;reproduction;sexual;synthetic
1
Fukuda, Nobuo;Honda, Shinya
ELSEVIER ACADEMIC PRESS INC
Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan
Review; Book Chapter
Natl Inst Adv Ind Sci & Technol
SAN DIEGO
null
null
Natl Inst Adv Ind Sci & Technol
Grants-in-Aid for Scientific Research;JSPS KAKENHI
Fukuda, N (corresponding author), Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan.
30
Fukuda, Nobuo;Honda, Shinya
11
1
500,713,500,003
Grants-in-Aid for Scientific Research [16K14497, 18K05424, 25820406] Funding Source: KAKEN;JSPS KAKENHI [25820406, 16K14497, 18K05424]
Japan
CHEMICAL AND SYNTHETIC BIOLOGY APPROACHES TO UNDERSTAND CELLULAR FUNCTIONS - PT A
Japan
null
null
Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan
0076-6879
Fukuda, N;Honda, S
null
nob-fukuda@aist.go.jp
synthetic gene expression circuits regulating sexual reproduction
2
S
Biochemistry & Molecular Biology;Cell Biology
alternative methods;ancient times;attractive means;basic guide;budding yeast Saccharomyces cerevisiae;CASSETTES;chapter;combine strain traits;common crossbreeding strategies;crossbreds via mating;crossbreeding;fermentative production;genetic modification;HETEROZYGOSITY;industry exhibit low sporulation rates;isolated yeast strains;isolation;limited crossbreeding efficiency;MAT alpha haploids via sporulation;MAT locus;MATa;MATa/alpha diploids;methods;modification;mutagenesis;numerous technical challenges;parental yeasts;protoplast fusion;purpose;researchers;sequence;several approaches;sexual reproduction;sexual reproduction machinery;sporulation;synthetic gene expression circuits;synthetic gene expression circuits regulating sexual reproduction;TRANSFORMATION;variety;yeast;yeast crossbreeding;yeast resources;yeast strains;yeast traits
Fukuda, N
CASSETTES;HETEROZYGOSITY;TRANSFORMATION
17
[Fukuda, Nobuo; Honda, Shinya] Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan.
This work was supported by JSPS KAKENHI Grant Number 25820406, 16K14497 and 18K05424.
alternative methods;ancient times;attractive means;basic guide;budding yeast Saccharomyces cerevisiae;chapter;combine strain traits;common crossbreeding strategies;crossbreds via mating;crossbreeding;fermentative production;genetic modification;industry exhibit low sporulation rates;isolated yeast strains;isolation;limited crossbreeding efficiency;MAT alpha haploids via sporulation;MAT locus;MATa;MATa/alpha diploids;methods;modification;mutagenesis;numerous technical challenges;parental yeasts;protoplast fusion;purpose;researchers;sequence;several approaches;sexual reproduction;sexual reproduction machinery;sporulation;synthetic gene expression circuits;variety;yeast;yeast crossbreeding;yeast resources;yeast strains;yeast traits
10.1016/0027-5107(90)90024-X;10.1016/0092-8674(82)90418-4;10.1021/acssynbio.7b00056;10.1021/acssynbio.8b00020;10.1021/sb400016j;10.1038/s41467-018-05106-7;10.1093/nar/20.6.1425;10.1111/1567-1364.12161;10.1128/MCB.01071-10;10.1128/MCB.11.10.5372;10.1146/annurev.genet.32.1.561;10.1186/1754-1611-7-27;10.1186/s13068-015-0216-0;10.1186/s13568-016-0216-x;10.1371/journal.pone.0068094;10.1534/genetics.108.089250;10.1534/genetics.166.2.653;10.19082/3592;10.2323/jgam.39.285
Natl Inst Adv Ind Sci & Technol
Fukuda, N;Honda, S
Fukuda, N: Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan
Fukuda, Nobuo;Honda, Shinya
16K14497;18K05424;25820406
22
978-0-12-818117-1
Japan
Natl Inst Adv Ind Sci & Technol
Fukuda, Nobuo
null
CASSETTES;HETEROZYGOSITY;TRANSFORMATION
Fukuda, Nobuo; Honda, Shinya;
null
Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan
Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan
null
null
null
1982;1983;1990;1991;1992;1993;1998;2000;2004;2008;2011;2013;2014;2015;2016;2017;2018
4
Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tsukuba, Ibaraki, Japan
Methods Enzymol.
Honda, Shinya
ELSEVIER ACADEMIC PRESS INC
,;a;acquire;alpha;alternative;an;ancient;and;approaches;are;as;attempting;attractive;based;basic;been;budding;cerevisiae;challenges;chapter;circuits;combine;common;construction;convert;crossbreds;crossbreeding;developed;diploids;directly;efficiency;enable;exhibit;expand;expression;fermentative;for;fusion;gene;genetic;guide;haploids;has;have;here;improve;in;including;industry;is;isolated;isolation;limited;locus;low;machinery;many;MAT;MATa;MATa/alpha;mate;mating;means;methods;modification;most;mutagenesis;numerous;of;on;parental;production;protoplast;provide;provides;purpose;rates;reproduction;require;researchers;resources;resulting;review;Saccharomyces;sequence;several;sexual;since;sporulation;strain;strains;strategies;subsequently;synthetic;technical;the;these;this;times;to;traits;unable;unfortunately;used;using;utilized;variety;via;we;who;widely;yeast;yeasts
Natl Inst Adv Ind Sci & Technol
The budding yeast Saccharomyces cerevisiae has been widely utilized in fermentative production since ancient times. Several approaches for modification of yeast traits have been developed, including mutagenesis, protoplast fusion, and genetic modification. Crossbreeding provides an attractive means to improve and combine strain traits based on sexual reproduction. Common crossbreeding strategies require the isolation of MATa and MAT alpha haploids via sporulation, as most of parental yeasts are MATa/alpha diploids and unable to mate directly. Unfortunately, many yeast strains used in industry exhibit low sporulation rates resulting in limited crossbreeding efficiency and numerous technical challenges. Here, we review the construction of synthetic gene expression circuits as a means to provide alternative methods for sporulation for yeast crossbreeding. These methods enable researchers to convert the sequence of the MAT locus and subsequently acquire crossbreds via mating of isolated yeast strains. The purpose of this chapter is to provide a basic guide for researchers who are attempting to expand the variety of yeast resources using the sexual reproduction machinery of yeast.
J-1872-2018;K-6894-2016
CASSETTES;HETEROZYGOSITY;TRANSFORMATION
4
null
null
14
CASSETTES;HETEROZYGOSITY;TRANSFORMATION
WOS:000500713500003
Natl Inst Adv Ind Sci & Technol, Ibaraki, Japan
Japan
2,019
null
0000-0001-7053-7194;0000-0002-7878-3944
null
Shukla, AK
English
null
ACS SYNTH BIOL;AMB EXPRESS;ANNU REV GENET;BIOTECHNOL BIOFUELS;CELL;CURR TOP DEV BIOL;Electron Physician;FEMS YEAST RES;GENETICS;J Biol Eng;J GEN APPL MICROBIOL;MOL CELL BIOL;MUTAT RES;NAT COMMUN;NUCLEIC ACIDS RES;PLOS ONE;YEAST
Fukuda, Nobuo;Honda, Shinya
2024-03-11 ER
Andersen, M R;Botstein, D;Brachmann, C B;Dashko, S;Duan, S F;Fukuda, N;Gelfand, B;Gietz, D;Haber, J E;Herskowitz, I;Hiraoka, M;Kumaran, R;Mayer, V W;Ogata, T;Ray, B L;Salari Roshanak;Snoek, T;Strathern, J N
BO1KX
Ibaraki, Japan
4
null
1
null
31,128,777
Fukuda, Nobuo;Honda, Shinya
METHOD ENZYMOL
Ibaraki, Japan
Lu, T K;Purcell, O;Siuti, P;Wang, J
10.1038/s41467-018-07144-7
4942
HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
4i45n5t6f6p2d73366746f2yg65205z4w3f59
Encryption and steganography of synthetic gene circuits
MIT
null
Lu, TK (corresponding author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Lu, TK (corresponding author), MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Lu, TK (corresponding author), MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA.
null
Lu, Timothy K;Purcell, Oliver;Siuti, Piro;Wang, Jerry
Multidisciplinary Sciences
Defense Advanced Research Projects Agency
WOS
Lu, T K
MIT, Cambridge, MA USA
9
and;circuits;encryption;gene;of;steganography;synthetic
1
Purcell, Oliver
NATURE PORTFOLIO
MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA
Article
MIT
BERLIN
null
null
MIT;Synthet Biol Ctr
Defense Advanced Research Projects Agency
Lu, TK (corresponding author), MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
null
Lu, Timothy K;Purcell, Oliver;Siuti, Piro;Wang, Jerry
18
3
450,924,300,004
Defense Advanced Research Projects Agency
USA
NATURE COMMUNICATIONS
USA;USA.;
null
null
MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA
null
Lu, T K;Purcell, O;Siuti, P;Wang, J
NOV 22
timlu@mit.edu
encryption;steganography;synthetic gene circuits
4
J
Science & Technology - Other Topics
approach;cells;circuit structure;circuit topology;CIRCUITS;CODE;emerging area;encryption;engineer living cells;first uses encryption;function;genes;goal;integration;intellectual property;interconnections;logic;MEMORY;overlapping uni-directional recombinase sites;PARTS;practicality;present two different approaches;relative strengths;research;second uses steganography;steganography;strategies;synthetic biologists use artificial gene circuits;synthetic circuits;synthetic gene circuits;synthetic genetic codes;third approach;unauthorized third party;weaknesses
Purcell, O
CODE;INTEGRATION;LOGIC;MEMORY;PARTS
null
[Purcell, Oliver; Wang, Jerry; Siuti, Piro; Lu, Timothy K.] MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA. [Lu, Timothy K.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Lu, Timothy K.] MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
This work was supported by the Defense Advanced Research Projects Agency. MK01 and MK02 cells were kind gifts from M. Kogenaru. The bi-stable switch was gift from J. Collins (MIT). We would like to thank J. W. Purcell for help with experimental work, and N. Roquet and F. Farzafard for reading and helping revise the manuscript.
approach;cells;circuit structure;circuit topology;circuits;emerging area;engineer living cells;first uses encryption;function;genes;goal;intellectual property;interconnections;overlapping uni-directional recombinase sites;practicality;present two different approaches;relative strengths;research;second uses steganography;strategies;synthetic biologists use artificial gene circuits;synthetic circuits;synthetic gene circuits;synthetic genetic codes;third approach;unauthorized third party;weaknesses
10.1002/anie.201105016;10.1007/0-387-25871-X_5;10.1016/j.copbio.2006.09.001;10.1016/j.jmb.2003.09.082;10.1016/S1097-2765(03)00444-1;10.1021/acssynbio.5b00216;10.1021/ja2054034;10.1038/35002131;10.1038/nature08817;10.1038/nature12148;10.1038/nbt.2401;10.1038/nbt.2510;10.1038/nbt1314;10.1038/nchembio.1680;10.1038/nchembio719;10.1038/ncomms7989;10.1038/nrm2005;10.1038/s41565-017-0004-z;10.1073/pnas.0900267106;10.1073/pnas.090527097;10.1073/pnas.1202344109;10.1093/nar/26.2.391;10.1099/mic.0.066308-0;10.1126/science.1205527;10.1126/science.1221761;10.1126/science.1232758;10.1126/science.aad8559;10.1126/science.aaf3639;10.1145/2508859.2516656;10.1186/1754-1611-8-2;[10.1038/NMETH.3147, 10.1038/nmeth.3147]
MIT
Lu, T K;Purcell, O;Siuti, P;Wang, J
Purcell, O: MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA
Lu, Timothy K
null
34
null
USA
MIT
Purcell, Oliver
Green Published, gold
CODE;INTEGRATION;LOGIC;MEMORY;PARTS
Purcell, Oliver; Wang, Jerry; Siuti, Piro; Lu, Timothy K.;
null
MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA
MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA
2041-1723
null
null
1998;2000;2002;2003;2004;2005;2006;2007;2009;2010;2011;2012;2013;2014;2015;2016;2018
7
MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Dept Elect Engn & Comp Sci, Res Lab Elect, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA
Nat. Commun.
Lu, Timothy K
NATURE PORTFOLIO
,;:;a;adding;also;an;and;approach;approaches;area;artificial;as;be;become;biologists;by;cells;circuit;circuits;codes;commercialized;contained;control;design;desirable;determine;different;difficult;discuss;each;emerging;encryption;engineer;engineered;first;for;function;further;gene;genes;genetic;goal;here;hide;implementation;important;in;increasingly;inspire;intellectual;interconnections;into;introduce;it;living;making;mask;more;obscure;of;overlapping;party;practicality;present;property;protect;recombinase;relative;research;scramble;second;sites;steganography;strategies;strengths;structure;synthetic;the;these;third;this;to;topology;two;unauthorized;uni-directional;use;uses;we;weaknesses;will;with
MIT
Synthetic biologists use artificial gene circuits to control and engineer living cells. As engineered cells become increasingly commercialized, it will be desirable to protect the intellectual property contained in these circuits. Here, we introduce strategies to hide the design of synthetic gene circuits, making it more difficult for an unauthorized third party to determine circuit structure and function. We present two different approaches: the first uses encryption by overlapping uni-directional recombinase sites to scramble circuit topology and the second uses steganography by adding genes and interconnections to obscure circuit topology. We also discuss a third approach: to use synthetic genetic codes to mask the function of synthetic circuits. For each approach, we discuss relative strengths, weaknesses, and practicality of implementation, with the goal to inspire further research into this important and emerging area.
G-4267-2012
CODE;INTEGRATION;LOGIC;MEMORY;PARTS
0
null
null
10
CODE;INTEGRATION;LOGIC;MEMORY;PARTS
WOS:000450924300004
MIT, Cambridge, MA USA
USA
2,018
null
0000-0002-1652-8702
null
null
English
null
ACS SYNTH BIOL;ANGEW CHEM INT EDIT;CIRC CAM TECHN;COMPLEXITY CHEM BIOL;CURR OPIN BIOTECH;J AM CHEM SOC;J Biol Eng;J MOL BIOL;MICROBIOL-SGM;MOL CELL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT NANOTECHNOL;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P ACM SIGSAC C COMP;P NATL ACAD SCI USA;PERMUTATION MATHWORL;SCIENCE;US patent
Lu, Timothy K;Purcell, Oliver;Siuti, Piro;Wang, Jerry
2024-03-11 ER
[Anonymous];An, W L;Bonchev, D;Bonnet, J;Caliando, B J;Chin, J W;Clark W.;Cleto, S;Daniel, R;Gardner, T S;Ghosh, P;Greiss, S;Groth, A C;Inside Secure;Kogenaru, M;Lapique, N;Lou, C B;Neumann, H;Nunes-Düby, S E;Ostrov, N;Rackham, O;Roquet, N;Siuti, P;Voigt, C A;Wang, K H;Weisstein E. W.;Wright, O;Xie, J M;Xie, Z;Yang, L
HB3CB
Cambridge, MA USA;Cambridge, MA USA.
7
null
1
null
30,467,337
Lu, Timothy K;Purcell, Oliver;Siuti, Piro;Wang, Jerry
NAT COMMUN
Cambridge, MA USA
Balázsi, G;Charlebois, D A;Hauser, K;Marshall, S
10.1073/pnas.1810858115
null
2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
126x383u173n224y202x6o5n1h3aa3r5r1a42
Multiscale effects of heating and cooling on genes and gene networks
SUNY Stony Brook
null
Balázsi, G (corresponding author), SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA.
null
Balazsi, Gabor;Charlebois, Daniel A;Hauser, Kevin;Marshall, Sylvia
Multidisciplinary Sciences
Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship [PDF-453977-2014]; NVIDIA Corporation Titan Xp GPU grant; NIH National Research Service Award Fellowship [F31-GM101946]; National Science Foundation Alliances for Graduate Education; Professoriate-Transformation Fellowship [HRD-1311318]; NIH/National Institute of General Medical Sciences Maximizing Investigators' Research Award [R35GM122561]; Laufer Center for Physical and Quantitative Biology
WOS
Balázsi, G
SUNY Stony Brook, Stony Brook, NY USA
115
and;cooling;Effects;gene;genes;heating;multiscale;networks;of;on
1
Charlebois, Daniel
NATL ACAD SCIENCES
SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA;SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA;SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA
Article
SUNY Stony Brook
WASHINGTON
null
null
SUNY Stony Brook
Laufer Center for Physical and Quantitative Biology;National Science Foundation Alliances for Graduate Education;Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship;NIH National Research Service Award Fellowship;NIH/National Institute of General Medical Sciences Maximizing Investigators' Research Award;NVIDIA Corporation Titan Xp GPU grant;Professoriate-Transformation Fellowship
Balázsi, G (corresponding author), SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA.
E10806
Balazsi, Gabor;Charlebois, Daniel A;Hauser, Kevin;Marshall, Sylvia
19
3
449,459,000,033
Laufer Center for Physical and Quantitative Biology;National Science Foundation Alliances for Graduate Education;Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship [PDF-453977-2014];NIH National Research Service Award Fellowship [F31-GM101946];NIH/National Institute of General Medical Sciences Maximizing Investigators' Research Award [R35GM122561];NVIDIA Corporation Titan Xp GPU grant;Professoriate-Transformation Fellowship [HRD-1311318]
USA
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
USA
null
null
SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA
0027-8424
Balázsi, G;Charlebois, D A;Hauser, K;Marshall, S
NOV 6
gabor.balazsi@stonybrook.edu
cooling;gene networks;genes;heating;multiscale effects
4
J
Science & Technology - Other Topics
agents;aid future applications;arrest;Arrhenius scaling;cell fate choice;cell fate decision;cellular decision;cellular protection;conformational dynamics;cooling;cooling affect expression;cope;corrupt gene;difficulties;dramatic gene expression bimodality;Effects;experimental observations;expression;FEEDBACK;feedback regulation;GENE;gene expression;gene network function;gene networks;genes;growth arrest;heating;isogenic cell populations;microbes;molecular-dynamics simulations;multiscale effects;multiscale models;noise;nonoptimal temperatures;nonstandard temperatures;ORGANISMS;overall;population dynamics;predictable ways;PROMOTER;reaction rates;regulatory networks;resistant cells;Saccharomyces cerevisiae;SACCHAROMYCES-CEREVISIAE;SHOCK RESPONSE;single genes;stress resistance;Synthetic gene circuit;synthetic gene circuits;temperature;temperature changes;TEMPERATURE COMPENSATION;temperature-dependent growth rates;TetR repressor;toggle switch;TRANSCRIPTION;understanding;yeast
Charlebois, D A
cellular decision;EXPRESSION;FEEDBACK;feedback regulation;NOISE;PROMOTER;REGULATORY NETWORKS;SACCHAROMYCES-CEREVISIAE;SHOCK RESPONSE;Synthetic gene circuit;temperature;TEMPERATURE COMPENSATION;toggle switch;TRANSCRIPTION;YEAST
E10797
[Charlebois, Daniel A.; Hauser, Kevin; Marshall, Sylvia; Balazsi, Gabor] SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA. [Marshall, Sylvia] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. [Balazsi, Gabor] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
We thank Todd B. Reynolds for the TBR1 strain, Kevin J. Verstrepen for the KV2695 strain, Sasha F. Levy for the Tsl1-GFP yeast strain, and Lin Chen for inserting the reporter construct into the TBR1 strain. We also thank Kingshuk Ghosh, Andre Ribeiro, Harold Bien, Oleksandra Romanyshyn, Teresa Charlebois, and the Paola Picotti group for helpful discussions; Tamas Szekely, Jr., and Zhihao Cai for acquiring the microfluidics time-lapse images; and the staff at the Flow Cytometry Core Research Facility at the Stony Brook University Hospital for assistance with cell-sorting experiments. This research was supported by a Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship (PDF-453977-2014) and NVIDIA Corporation Titan Xp GPU grant (to D.A.C.), NIH National Research Service Award Fellowship (F31-GM101946) and National Science Foundation Alliances for Graduate Education and the Professoriate-Transformation Fellowship (HRD-1311318) (to K.H.), NIH/National Institute of General Medical Sciences Maximizing Investigators' Research Award Grant R35GM122561 (to G.B.), and the Laufer Center for Physical and Quantitative Biology.
agents;aid future applications;arrest;Arrhenius scaling;cell fate choice;cell fate decision;cellular protection;conformational dynamics;cooling;cooling affect expression;cope;corrupt gene;difficulties;dramatic gene expression bimodality;effects;experimental observations;gene;gene expression;gene network function;genes;growth arrest;heating;isogenic cell populations;microbes;molecular-dynamics simulations;multiscale models;nonoptimal temperatures;nonstandard temperatures;organisms;overall;population dynamics;predictable ways;reaction rates;resistant cells;Saccharomyces cerevisiae;single genes;stress resistance;synthetic gene circuits;temperature changes;temperature-dependent growth rates;TetR repressor;understanding
10.1002/(SICI)1521-1878(199805)20:5<433::AID-BIES10>3.0.CO;2-2;10.1002/biot.201200085;10.1006/jmbi.1994.1468;10.1007/s10867-012-9264-x;10.1016/0378-1119(83)90046-X;10.1016/j.bpj.2011.05.059;10.1016/j.ceb.2013.07.007;10.1016/j.cell.2009.12.001;10.1016/j.cell.2013.02.050;10.1016/j.cell.2014.02.033;10.1016/j.cell.2016.03.006;10.1016/j.celrep.2014.05.018;10.1016/j.molcel.2006.11.003;10.1016/j.molcel.2010.10.006;10.1016/S0022-2836(02)00994-4;10.1016/S0092-8674(03)00346-5;10.1021/acssynbio.5b00154;10.1021/jp0674468;10.1038/346329a0;10.1038/35002125;10.1038/35002131;10.1038/35014651;10.1038/msb.2011.21;10.1038/msb4100173;10.1038/nature01546;10.1038/nature04194;10.1038/nature04640;10.1038/nature04785;10.1038/nature07389;10.1038/nature09937;10.1038/nchembio.1411;10.1038/nchembio.218;10.1038/s41559-016-0016;10.1038/sj/cdd/4400942;10.1042/BJ20060166;10.1046/j.1365-2958.1999.01389.x;10.1073/pnas.0307571101;10.1073/pnas.0408031102;10.1073/pnas.0608451104;10.1073/pnas.0809901106;10.1073/pnas.1114477108;10.1073/pnas.1316298111;10.1073/pnas.1332628100;10.1073/pnas.1508521112;10.1073/pnas.1510328112;10.1073/pnas.1514383113;10.1073/pnas.1517109113;10.1074/jbc.R117.804641;10.1091/mbc.11.12.4241;10.1093/femsle/fnv082;10.1093/nar/25.14.2723;10.1093/nar/gkn545;10.1093/nar/gks583;10.1093/nar/gkv1091;10.1103/PhysRevE.89.052708;10.1109/CDC.2013.6760078;10.1111/j.1365-2958.2012.08192.x;10.1126/science.1154456;10.1126/science.1158684;10.1126/science.1189015;10.1126/science.1192588;10.1126/science.291.5505.878;10.1126/science.aai7825;10.1128/AEM.71.8.4531-4538.2005;10.1128/JB.184.18.5058-5066.2002;10.1128/MCB.13.2.1034;10.1128/MMBR.05018-11;10.1128/MMBR.69.2.326-356.2005;10.1146/annurev.mi.48.100194.002021;10.1186/1472-6750-7-6;10.1186/s12867-015-0048-2;10.1371/journal.pbio.1001325;10.1371/journal.pcbi.1002187;10.1371/journal.pcbi.1002480;10.1371/journal.pcbi.1003979;10.1371/journal.pcbi.1005174;10.1371/journal.pgen.1000673;10.15252/msb.20156185;10.1534/genetics.111.128033;10.1534/genetics.111.130765;10.3109/07420529709001471
SUNY Stony Brook
Balázsi, G;Charlebois, D A;Hauser, K;Marshall, S
Charlebois, D A: SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA
Charlebois, Daniel
F31-GM101946;HRD-1311318;PDF-453977-2014;R35GM122561
84
null
USA
SUNY Stony Brook
Charlebois, Daniel A
hybrid, Green Published, Green Submitted
EXPRESSION;FEEDBACK;PROMOTER;REGULATORY NETWORKS;SACCHAROMYCES-CEREVISIAE;SHOCK RESPONSE;TEMPERATURE COMPENSATION;TOGGLE SWITCH;TRANSCRIPTION;YEAST
Charlebois, Daniel A.; Hauser, Kevin; Marshall, Sylvia; Balazsi, Gabor;
null
SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA;SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA;SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA
SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA;SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA;SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA
null
cellular decision;feedback regulation;noise;Synthetic gene circuit;temperature
45
1983;1990;1993;1994;1997;1998;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
31
SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA
Proc. Natl. Acad. Sci. U. S. A.
Balazsi, Gabor
NATL ACAD SCIENCES
,;a;abolishes;affect;agents;aid;alters;and;applications;arrest;Arrhenius;as;between;bimodality;both;but;captured;cell;cells;cellular;cerevisiae;changes;choice;circuits;computationally;conformational;cooling;cope;corrupt;creates;creating;decision;difficulties;discovered;dramatic;dynamics;effects;engineered;experimental;explaining;expression;fate;fully;function;future;gene;genes;growth;heating;here;how;in;incorporating;induce;involves;isogenic;may;microbes;models;molecular-dynamics;most;multiscale;must;network;networks;nonoptimal;nonstandard;not;observations;of;organisms;overall;population;populations;predictable;protection;rates;reaction;repressor;resistance;resistant;revealed;Saccharomyces;scaling;simulations;single;stress;study;subjects;synthetic;temperature;temperature-dependent;temperatures;TetR;that;the;this;those;understanding;ways;we;which;with
SUNY Stony Brook
Most organisms must cope with temperature changes. This involves genes and gene networks both as subjects and agents of cellular protection, creating difficulties in understanding. Here, we study how heating and cooling affect expression of single genes and synthetic gene circuits in Saccharomyces cerevisiae. We discovered that nonoptimal temperatures induce a cell fate choice between stress resistance and growth arrest. This creates dramatic gene expression bimodality in isogenic cell populations, as arrest abolishes gene expression. Multiscale models incorporating population dynamics, temperature-dependent growth rates, and Arrhenius scaling of reaction rates captured the effects of cooling, but not those of heating in resistant cells. Molecular-dynamics simulations revealed how heating alters the conformational dynamics of the TetR repressor, fully explaining the experimental observations. Overall, nonoptimal temperatures induce a cell fate decision and corrupt gene and gene network function in computationally predictable ways, which may aid future applications of engineered microbes in nonstandard temperatures.
R-8264-2016
EXPRESSION;FEEDBACK;PROMOTER;REGULATORY NETWORKS;SACCHAROMYCES-CEREVISIAE;SHOCK RESPONSE;TEMPERATURE-COMPENSATION;TOGGLE SWITCH;TRANSCRIPTION;YEAST
4
null
cellular decision;feedback regulation;noise;Synthetic gene circuit;temperature
10
SACCHAROMYCES-CEREVISIAE;YEAST;cellular decision;EXPRESSION;FEEDBACK;FEEDBACK-REGULATION;NOISE;PROMOTER;REGULATORY NETWORKS;SHOCK RESPONSE;synthetic gene circuits;temperature;TEMPERATURE COMPENSATION;toggle switch;TRANSCRIPTION
WOS:000449459000033
SUNY Stony Brook, Stony Brook, NY USA
USA
2,018
null
0000-0001-7426-1789
null
null
English
null
ACS SYNTH BIOL;ANNU REV MICROBIOL;APPL ENVIRON MICROB;BIOCHEM J;BIOESSAYS;BIOPHYS J;BIOTECHNOL J;BMC BIOTECHNOL;BMC MOL BIOL;CELL;CELL DEATH DIFFER;CELL REP;CHRONOBIOL INT;CURR OPIN CELL BIOL;FEMS MICROBIOL LETT;GENE;GENETICS;IEEE DECIS CONTR P;J BACTERIOL;J BIOL CHEM;J BIOL PHYS;J MOL BIOL;J PHYS CHEM B;MICROBIOL MOL BIOL R;MOL BIOL CELL;MOL CELL;MOL CELL BIOL;MOL MICROBIOL;MOL SYST BIOL;NAT CHEM BIOL;NAT ECOL EVOL;NAT STRUCT BIOL;NATURE;NEGATIVE FEEDBACK FA;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV E;PLOS BIOL;PLOS COMPUT BIOL;PLOS GENET;SCIENCE;WSEAS T BIOL BIOMED
Balazsi, Gabor;Charlebois, Daniel A;Hauser, Kevin;Marshall, Sylvia
2024-03-11 ER
Abudugupur, A;Al-Fageeh, M B;Anderson, J C;Arnaud, O;Atkinson, M R;Austin, D W;Baron, U;Basu, S;Becskei, A;Bertrand, K P;Blake, W J;Botstein, D;Cao, Y X L;Cardinale, S;Charlebois Da.;Charlebois, D A;Chen, L;Delorme-Axford, E;Diao, J C;Dill, K A;Dowell, R D;Dunlop, M J;Elowitz, M B;Ferrell, J E;Gardner, T S;Gasch, A P;González, C;Hauser, K;Heiland, I;Hillen, W;Hussain, F;Isaacs, F J;Jo, M C;Klumpp, S;Leuenberger, P;Levine, M;Levy, S F;Li, G W;Madrid, C;Marciano, D C;Mensonides, F I C;Mihalik, A;Morano, K A;Murphy, K F;Muthukrishnan, A B;Neupert, J;Nevozhay, D;Newman, J R S;Octavio, L M;Oliveira, S M D;Orth, P;Perezmartin, J;Ptashne, M;Pyatrikas, D V;Raboy, B;Ramos, J L;Reynolds, T B;Richter, K;Ro, D K;Rosenfeld, N;Rowley, A;Ruoff, P;Sawle, L;Saxena, P;Scott, M;Seidel, U;Sen, S;Slomovic, S;Stanton, B C;Stricker, J;Tagkopoulos, I;Tan, C;Thieffry, D;Verghese, J;Voordeckers, K;Watson, E;Windbichler, N;Yaakov, G;Yu, H Y;Zechner, C;Zhou, X
GZ5KM
Stony Brook, NY USA
34
null
1
null
30,341,217
Balazsi, Gabor;Charlebois, Daniel A;Hauser, Kevin;Marshall, Sylvia
P NATL ACAD SCI USA
Stony Brook, NY USA
Pardee, K
10.1016/j.bej.2018.07.008
null
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS
o411w6m3mx3r401m271440p2m96p5s5r5367
Perspective: Solidifying the impact of cell-free synthetic biology through lyophilization
Univ Toronto
null
Pardee, K (corresponding author), Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada.
null
Pardee, Keith
Biotechnology & Applied Microbiology;Engineering, Chemical
NSERC [RGPIN-2016-06352]; CIHR [201610FDN-375469]; Bill and Melinda Gates Foundation: Grand Challenges Explorations [OPP1160667]; University of Toronto's Connaught Fund; University of Toronto's Medicine by Design initiative; Canada First Research Excellence Fund; Bill and Melinda Gates Foundation [OPP1160667] Funding Source: Bill and Melinda Gates Foundation
WOS
Pardee, K
Univ Toronto, Toronto ON, Canada
138
:;biology;Cell-Free;impact;lyophilization;of;perspective;Solidifying;synthetic;the;through
1
null
ELSEVIER
Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada
Article
Univ Toronto
AMSTERDAM
null
null
Univ Toronto
Bill and Melinda Gates Foundation;Bill and Melinda Gates Foundation: Grand Challenges Explorations;Canada First Research Excellence Fund;CIHR;NSERC;University of Toronto's Connaught Fund;University of Toronto's Medicine by Design initiative
Pardee, K (corresponding author), Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada.
97
Pardee, Keith
29
1
445,980,900,011
Bill and Melinda Gates Foundation [OPP1160667] Funding Source: Bill and Melinda Gates Foundation;Bill and Melinda Gates Foundation: Grand Challenges Explorations [OPP1160667];Canada First Research Excellence Fund;CIHR [201610FDN-375469];NSERC [RGPIN-2016-06352];University of Toronto's Connaught Fund;University of Toronto's Medicine by Design initiative
Canada
BIOCHEMICAL ENGINEERING JOURNAL
Canada
null
null
Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada
1369-703X
Pardee, K
OCT 15
keith.pardee@utoronto.ca
cell-free synthetic biology;impact;lyophilization;perspective
1
J
Biotechnology & Applied Microbiology;Engineering
ability;abiotic format;advantage;application-focused domain builds;biosafe mode outside;Biosensor;C 2018;cell-free biochemistry;Cell-free synthetic biology;cell-free systems;cellular environments;challenges;chief;community;creative ways;decades;diagnostics;dried pellets;Elsevier B.V;embedded paper-based reactions;EXTRACT PREPARATION;FREE EXPRESSION;FREE PLATFORM;FREE PROTEIN-SYNTHESIS;Freeze-dried cell-free reactions;IMPACT;laboratory;longstanding challenge;lyophilization;MOLECULES;new branch;new efforts;new ideas;newfound venue;opportunities;Paper-based;perspective;poised synthetic gene networks;Portable therapeutic manufacturing;potential;proof-of-concept demonstrations;PROTEIN EXPRESSION;PURIFICATION;recent work;Sensors;significant excitement;synthetic biology;synthetic gene networks outside;taken;thoughts;tools;TRANSCRIPTION-TRANSLATION SYSTEM;translation systems;unexpected advantages;VACCINES;virus;vitro transcription
Pardee, K
Biosensor;Cell-free synthetic biology;Diagnostics;EXTRACT PREPARATION;FREE EXPRESSION;FREE PLATFORM;FREE PROTEIN-SYNTHESIS;Freeze-dried cell-free reactions;MOLECULES;Paper-based;Portable therapeutic manufacturing;PURIFICATION;Sensors;TRANSCRIPTION-TRANSLATION SYSTEM;VACCINES;virus
91
[Pardee, Keith] Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada.
I would like to thank Hamed Tinafar and Margot Karlikow for their review and helpful comments on the manuscript. Related work in the Pardee lab is support by funding from NSERC (RGPIN-2016-06352), CIHR (201610FDN-375469), Bill and Melinda Gates Foundation: Grand Challenges Explorations (Round 17, OPP1160667), the University of Toronto's Connaught Fund and the University of Toronto's Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund.
ability;abiotic format;advantage;application-focused domain builds;biosafe mode outside;cell-free biochemistry;cell-free synthetic biology;cell-free systems;cellular environments;challenges;chief;community;creative ways;decades;dried pellets;embedded paper-based reactions;laboratory;longstanding challenge;new branch;new efforts;new ideas;newfound venue;opportunities;poised synthetic gene networks;potential;proof-of-concept demonstrations;protein expression;recent work;significant excitement;synthetic biology;synthetic gene networks outside;taken;thoughts;tools;translation systems;unexpected advantages;vitro transcription
10.1002/biot.201100155;10.1002/biot.201500214;10.1002/biot.201500237;10.1002/biot.201600678;10.1002/bit.10827;10.1002/bit.10865;10.1002/bit.21567;10.1002/bit.21716;10.1002/bit.24581;10.1002/bit.24947;10.1002/bit.25502;10.1002/bit.26253;10.1002/bit.26439;10.1002/bit.26502;10.1002/btm2.10049;10.1002/btpr.1509;10.1002/btpr.744;10.1002/wnan.1234;10.1006/prep.2001.1400;10.1007/978-1-59745-196-3_15;10.1007/978-1-60327-331-2_12;10.1007/978-1-60327-331-2_2;10.1016/j.bej.2017.11.013;10.1016/j.biochi.2013.11.025;10.1016/j.cell.2014.10.002;10.1016/j.cell.2014.10.004;10.1016/j.cell.2016.04.059;10.1016/j.cell.2016.09.013;10.1016/j.febslet.2014.05.061;10.1016/j.jbiosc.2016.07.015;10.1016/j.jbiotec.2006.05.014;10.1016/j.jbiotec.2011.04.011;10.1016/j.jmb.2011.08.055;10.1016/j.pep.2005.09.021;10.1016/j.pep.2010.01.016;10.1016/j.taap.2018.02.016;10.1016/j.tibtech.2013.09.002;10.1016/j.ymben.2016.09.008;10.1016/S0014-5793(02)02383-9;10.1016/S0956-5663(01)00303-7;10.1021/ac100231a;10.1021/acs.analchem.6b04034;10.1021/acssynbio.5b00296;10.1021/acssynbio.7b00001;10.1021/acssynbio.7b00219;10.1021/acssynbio.7b00253;10.1021/bc100367u;10.1021/bi00905a029;10.1021/bp049789y;10.1021/bp060110v;10.1021/es203511k;10.1021/nl062560n;10.1021/sb200016s;10.1021/sb300049p;10.1021/sb400206c;10.1023/B:JSFG.0000029204.57846.7d;10.1038/90802;10.1038/msb.2008.57;10.1038/msb.2011.55;10.1038/nature24648;10.1038/nchem.2484;10.1038/nrendo.2010.87;10.1038/s41467-018-03469-5;10.1038/s41598-018-27846-8;10.1038/srep08663;10.1038/srep30442;10.1039/c3mb70304e;10.1073/pnas.0905735106;10.1073/pnas.1308701110;10.1073/pnas.1510533112;10.1073/pnas.1715806115;10.1084/jem.186.3.393;10.1093/nar/gkq377;10.1093/synbio/ysy002;10.1093/synbio/ysy003;10.1098/rsif.2016.1039;10.1126/science.290.5499.2148;10.1126/science.aag0804;10.1126/science.aam9321;10.1128/IAI.68.2.986-989.2000;10.1128/JVI.66.11.6527-6532.1992;10.1146/annurev.ge.07.120173.001411;10.1182/blood-2006-07-030593;10.1186/1475-2859-10-56;10.1371/journal.pone.0106232;10.2144/0000113924;10.2144/000114158;10.3389/fmicb.2018.01146;10.3791/50762;10.4161/mabs.4.2.19202;[10.1038/NCHEMBIO.2514, 10.1038/nchembio.2514];[10.1039/c2ra01376b, 10.1039/C2RA01376B]
Univ Toronto
Pardee, K
Pardee, K: Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada
null
201610FDN-375469;OPP1160667;RGPIN-2016-06352
93
null
Canada
Univ Toronto
Pardee, Keith
Green Published, hybrid
BIOSENSOR;EXTRACT PREPARATION;FREE EXPRESSION;FREE PLATFORM;FREE PROTEIN-SYNTHESIS;MOLECULES;PURIFICATION;TRANSCRIPTION-TRANSLATION SYSTEM;VACCINES;VIRUS
Pardee, Keith;
null
Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada
Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada
1873-295X
Cell-free synthetic biology;Diagnostics;Freeze-dried cell-free reactions;Paper-based;Portable therapeutic manufacturing;Sensors
null
1963;1973;1992;1997;2000;2001;2002;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
33
Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada
Biochem. Eng. J.
Pardee, Keith
ELSEVIER
,;a;ability;abiotic;advantage;advantages;ahead;among;an;and;application-focused;based;begun;biochemistry;biology;biosafe;branch;brought;builds;by;cell-free;cellular;challenge;challenges;chief;community;creative;decades;demonstrations;deploy;domain;dried;efforts;embedded;encoded;environments;even;excitement;exciting;explore;expression;extend;extended;field;for;format;freeze-dried;freeze-drying;gene;genetically;has;have;here;how;I;ideas;important;in;into;is;laboratory;longstanding;mode;my;networks;new;newfound;of;on;operate;opportunities;or;outside;paper-based;pellets;perhaps;poised;potential;proof-of-concept;protein;provide;reactions;recent;significant;solved;sterile;synthetic;systems;taken;the;there;these;this;thoughts;to;together;tools;transcription;translation;unexpected;venue;vitro;ways;work
Univ Toronto
Cell-free synthetic biology is an exciting and new branch in the field of synthetic biology. Based on in vitro transcription and translation systems, this application-focused domain builds on decades of cell-free biochemistry and protein expression to operate synthetic gene networks outside of cellular environments. This has brought new and perhaps even unexpected advantages. Chief among these is the ability to operate genetically encoded tools in a sterile and abiotic format. Recent work has extended this advantage by freeze-drying these cell-free systems into dried pellets or embedded paper-based reactions. Taken together, these new ideas have solved the longstanding challenge of how to deploy poised synthetic gene networks in a biosafe mode outside of the laboratory. There is significant excitement in the potential of this newfound venue and the community has begun to extend proof-of-concept demonstrations in important and creative ways. Here I explore these new efforts and provide my thoughts on the challenges and opportunities ahead for freeze-dried, cell-free synthetic biology.
null
BIOSENSOR;EXTRACT PREPARATION;FREE EXPRESSION;FREE PLATFORM;FREE PROTEIN-SYNTHESIS;MOLECULES;PURIFICATION;TRANSCRIPTION-TRANSLATION SYSTEM;VACCINE;VIRUS
2
null
Cell-free synthetic biology;Diagnostics;Freeze-dried cell-free reactions;Paper-based;Portable therapeutic manufacturing;Sensors
7
Biosensor;Cell-free synthetic biology;Diagnostics;EXTRACT PREPARATION;FREE EXPRESSION;FREE PLATFORM;FREE PROTEIN-SYNTHESIS;Freeze-dried cell-free reactions;MOLECULES;Paper-based;Portable therapeutic manufacturing;PURIFICATION;SENSOR;TRANSCRIPTION-TRANSLATION SYSTEM;VACCINE;virus
WOS:000445980900011
Univ Toronto, Toronto ON, Canada
Canada
2,018
null
null
null
null
English
null
ACS SYNTH BIOL;ANAL CHEM;ANNU REV GENET;BIOCHEM ENG J;BIOCHEMISTRY-US;BIOCHIMIE;BIOCONJUGATE CHEM;BIOENG TRANSL MED;BIOSENS BIOELECTRON;BIOTECHNIQUES;BIOTECHNOL BIOENG;BIOTECHNOL J;BIOTECHNOL PROGR;BLOOD;CELL;CHANDLER M;ENVIRON SCI TECHNOL;FEBS LETT;FRONT MICROBIOL;INFECT IMMUN;J BIOSCI BIOENG;J BIOTECHNOL;J EXP MED;J MOL BIOL;J R SOC INTERFACE;J VIROL;Journal of Structural and Functional Genomics;JOVE-J VIS EXP;MABS-AUSTIN;METAB ENG;METHODS MOL BIOL;MICROB CELL FACT;MOL BIOSYST;MOL SYST BIOL;NANO LETT;NAT BIOTECHNOL;NAT CHEM;NAT CHEM BIOL;NAT COMMUN;NAT REV ENDOCRINOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;PROTEIN EXPRES PURIF;RSC ADV;SCI REP-UK;SCIENCE;SYN BIOL;TOXICOL APPL PHARM;TRENDS BIOTECHNOL;WIRES NANOMED NANOBI
Pardee, Keith
2024-03-11 ER
Asahara, H;Bretthauer, R K;Bundy, B C;Buntru, M;Burgenson, D;Caschera, F;Chandler M.;Choi, S H;Clomburg, J M;Daube, S S;Didovyk, A;Duyen, T T M;Ezure, T;Failmezger, J;Garamella, J;Goerke, A R;Gootenberg, J S;Green, A A;Harbers, M;Huppa, J B;Jain, V;Jewett, M C;Jiang, X P;Kanter, G;Karig, D K;Kelwick, R;Kigawa Takanori;Kim, D M;Kim, T W;Kwon, Y C;Lee, K H;Lee, M S;Li, J;Liu, D V;Lu, Y;Makino, S;Martemyanov, K A;Martin, R W;Matthies, D;Mikami, S;Moore, S J;Ong, L L;Pardee, K;Patel, K G;Rohovie, M J;Rustad, M;Saeidi, N;Salehi, A S M;Schoborg, J A;Shimizu, Y;Shin, J;Shinoda, T;Shrestha, P;Siegfried, K;Sitararnan Kalavathy;Smith, M T;Soto, A M;Struss, A;Sullivan, C J;Sun, Z Z;Takahashi, M K;Tanrikulu, I C;Tran, K;Villarreal, F;Wang, H;Welsh, J P;Wen, K Y;Xi, J A;Yan, L;Yang, W C;Yildiz, I;Yin, G;Yonekura, K;Young, C L;Zhao, Q J;Zubay, G
GV3FX
Toronto ON, Canada
47
null
1
null
30,740,032
Pardee, Keith
BIOCHEM ENG J
Toronto ON, Canada
Du, Y M;Fang, N;Liu, X F;Liu, X M;Liu, Y H;Lu, T G;Sui, J K;Wang, C K;Wang, W J;Yan, N;Zhang, H B;Zhang, Z F
10.3390/molecules23102511
2511
ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
d6cfe735q4b3v3504j5i4h4u5v6x5y3o6q4q
Formation of α- and β-Cembratriene-Diols in Tobacco (<i>Nicotiana tabacum</i> L.) Is Regulated by Jasmonate-Signaling Components via Manipulating Multiple Cembranoid Synthetic Genes
Chinese Acad Agr Sci
null
Zhang, HB (corresponding author), Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China.
null
Du, Yongmei;Fang, Ning;Liu, Xiaofeng;Liu, Xinmin;Liu, Yanhua;Lu, Tiegang;Sui, Jinkai;Wang, Chunkai;Wang, Wenjing;Yan, Ning;Zhang, Hongbo;Zhang, Huai-Bao;Zhang, Zhongfeng
Biochemistry & Molecular Biology;Chemistry, Multidisciplinary
Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (Elite youth program) [ASTIP-TRIC05]; National Natural Science Foundation of China [31801279]; Fundamental Research Funds for Chinese Academy of Agricultural Sciences [Y2017JC21, 1610232016018, Y2017LM15]
WOS
Zhang, H B
Chinese Acad Agr Sci, Beijing, Peoples R China;Chinese Acad Agr Sci, Qingdao, Peoples R China
23
(<i>Nicotiana;and;by;Cembranoid;Components;formation;genes;in;is;Jasmonate-Signaling;L;Manipulating;Multiple;of;Regulated;synthetic;tabacum</i>;Tobacco;via;α-;β-Cembratriene-Diols
1
Fang, Ning;Wang, Wenjing
MDPI
Chinese Acad Agr Sci, Biotechnol Res Inst, Beijing 100081, Peoples R China;Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China
Article
Chinese Acad Agr Sci
BASEL
null
null
Chinese Acad Agr Sci
Fundamental Research Funds for Chinese Academy of Agricultural Sciences;National Natural Science Foundation of China;Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (Elite youth program)
Zhang, HB (corresponding author), Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China.
null
Du, Yongmei;Fang, Ning;Liu, Xiaofeng;Liu, Xinmin;Liu, Yanhua;Lu, Tiegang;Sui, Jinkai;Wang, Chunkai;Wang, Wenjing;Yan, Ning;Zhang, Hongbo;Zhang, Huai-Bao;Zhang, Zhongfeng
26
2
451,201,400,107
Fundamental Research Funds for Chinese Academy of Agricultural Sciences [Y2017JC21, 1610232016018, Y2017LM15];National Natural Science Foundation of China [31801279];Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (Elite youth program) [ASTIP-TRIC05]
China
MOLECULES
China
null
null
Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China
null
Du, Y M;Fang, N;Liu, X F;Liu, X M;Liu, Y H;Lu, T G;Sui, J K;Wang, C K;Wang, W J;Yan, N;Zhang, H B;Zhang, Z F
OCT
duyongmei@caas.cn;fangning010@163.com;liuxiaofeng626@126.com;liuxinmin@caas.cn;liuyanhua@caas.cn;lutiegang@caas.cn;suijinkai@163.com;wangchunkai1990@outlook.com;wangwenjing@caas.cn;yanning@caas.cn;zhanghongbo@caas.cn;zhanghuaibao@caas.cn;zhangzhongfeng@caas.cn
formation;Jasmonate-Signaling Components via;Multiple Cembranoid Synthetic Genes;Tobacco (<i>Nicotiana tabacum</i> L;α-;β-Cembratriene-Diols
12
J
Biochemistry & Molecular Biology;Chemistry
anti-nicotine addiction;ARABIDOPSIS;bioactive derivative;biosynthesis;cembranoid formation;cembranoid production;cembranoid synthetic genes;cembranoid synthetic genes CBTS;cembranoids;cembratriene-diol;cembratriene-diol formation;cembratriene-diol synthetic genes;cembratriene-diols;cembratriene-diols' formation;COI1;critical role;defense responses;display critical roles;DOMAIN PROTEINS INTERACT;downstream regulators MYC2a;dysfunction;encoding MYB transcription factor MYB305;enzymes;expression;findings;formation;gene encoding bHLH transcription factor MYC2a;GLANDULAR TRICHOME;great importance;group;JA;JA (i.e. JA-Ile);JA-signaling components;jasmonate;Jasmonate-Signaling Components via;METABOLISM;molecular regulatory mechanism underlying cembranoid synthesis;Multiple Cembranoid Synthetic Genes;MYB305;MYC2;N. tabacum cv;natural diterpenoid compounds;neuron protection;Nicotiana (tobacco) species display activities;NtLTP1;over-expressing;P450;pharmaceutical potentials;physiological process;phytohormone jasmonic acid (JA);PLANT STRESS-RESPONSE;plants;receptor protein;regulating cembratriene-diol formation;regulating cembratriene-diols' formation;regulatory mechanism;ROLES;secondary metabolism;studies;study;taken;TN90;tobacco;Tobacco (<i>Nicotiana tabacum</i> L;TRANSCRIPTION;TRICHOME INITIATION;trichome secretion;unknown;upregulate;α-;β-Cembratriene-Diols
Sui, J K
ARABIDOPSIS;BIOSYNTHESIS;cembratriene-diol;COI1;DEFENSE RESPONSES;DOMAIN PROTEINS INTERACT;GLANDULAR TRICHOME;jasmonate;METABOLISM;MYC2;PLANT STRESS-RESPONSE;secondary metabolism;tobacco;TRICHOME INITIATION
null
[Sui, Jinkai; Wang, Chunkai; Liu, Xiaofeng; Fang, Ning; Liu, Yanhua; Wang, Wenjing; Yan, Ning; Zhang, Huai-Bao; Du, Yongmei; Liu, Xinmin; Zhang, Zhongfeng; Zhang, Hongbo] Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China. [Lu, Tiegang] Chinese Acad Agr Sci, Biotechnol Res Inst, Beijing 100081, Peoples R China.
This work was supported by the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (Elite youth program to H.Z., ASTIP-TRIC05), the National Natural Science Foundation of China (Grant No. 31801279) and the Fundamental Research Funds for Chinese Academy of Agricultural Sciences (Y2017JC21, 1610232016018, Y2017LM15).
anti-nicotine addiction;bioactive derivative;cembranoid formation;cembranoid production;cembranoid synthetic genes;cembranoid synthetic genes CBTS;cembranoids;cembratriene-diol formation;cembratriene-diol synthetic genes;cembratriene-diols;cembratriene-diols' formation;COI1;critical role;display critical roles;downstream regulators MYC2a;dysfunction;encoding MYB transcription factor MYB305;enzymes;expression;findings;gene encoding bHLH transcription factor MYC2a;great importance;group;JA;JA (i.e. JA-Ile);JA-signaling components;molecular regulatory mechanism underlying cembranoid synthesis;MYB305;N. tabacum cv;natural diterpenoid compounds;neuron protection;Nicotiana (tobacco) species display activities;NtLTP1;over-expressing;P450;pharmaceutical potentials;physiological process;phytohormone jasmonic acid (JA);plants;receptor protein;regulating cembratriene-diol formation;regulating cembratriene-diols' formation;regulatory mechanism;roles;studies;study;taken;TN90;tobacco;transcription;trichome secretion;unknown;upregulate
10.1007/s00425-002-0904-4;10.1007/s00442-002-0924-6;10.1007/s11103-007-9149-8;10.1016/j.bmc.2017.05.028;10.1016/j.celrep.2017.04.057;10.1016/j.indcrop.2015.12.031;10.1016/j.pbi.2009.07.015;10.1016/j.tplants.2012.03.001;10.1038/86770;10.1038/nature05960;10.1038/nature06006;10.1038/nature09430;10.1038/ncomms13056;10.1038/nprot.2008.73;10.1042/bj0570508;10.1046/j.1365-313X.2002.01432.x;10.1073/pnas.0802332105;10.1080/17429145.2010.544779;10.1093/aob/mcm079;10.1093/aob/mct067;10.1093/jxb/erp270;10.1093/jxb/eru084;10.1093/jxb/erw495;10.1093/jxb/erx068;10.1093/mp/ssr056;10.1093/mp/sss128;10.1093/pcp/pcy004;10.1101/gad.297704;10.1104/pp.103.027086;10.1104/pp.108.125385;10.1104/pp.17.00727;10.1105/tpc.000679;10.1105/tpc.017954;10.1105/tpc.022319;10.1105/tpc.106.048017;10.1105/tpc.108.060079;10.1105/tpc.111.083089;10.1105/tpc.111.083261;10.1105/tpc.112.098749;10.1105/tpc.8.9.1519;10.1111/j.1365-313X.2006.02851.x;10.1111/j.1365-313X.2008.03432.x;10.1111/j.1365-313X.2011.04875.x;10.1111/j.1365-313X.2011.04886.x;10.1111/j.1469-8137.2010.03466.x;10.1111/nph.14205;10.1126/science.1182612;10.1126/science.280.5366.1091;10.1186/1746-4811-9-46;10.1242/dev.016873;10.1242/dev.030585;10.4161/psb.5.2.11214;10.4161/psb.6.12.18120
Chinese Acad Agr Sci
Du, Y M;Fang, N;Liu, X F;Liu, X M;Liu, Y H;Lu, T G;Sui, J K;Wang, C K;Wang, W J;Yan, N;Zhang, H B;Zhang, Z F
Sui, J K: Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China
Fang, Ning;liu, yan;Liu, Yiming;Wang, Wenjing;wang, xu
1610232016018;31801279;ASTIP-TRIC05;Y2017JC21;Y2017LM15
54
null
China
Chinese Acad Agr Sci
Sui, Jinkai
Green Published, Green Submitted, gold
ARABIDOPSIS;BIOSYNTHESIS;COI1;DEFENSE RESPONSES;DOMAIN PROTEINS INTERACT;GLANDULAR TRICHOME;METABOLISM;MYC2;PLANT STRESS-RESPONSE;TRICHOME INITIATION
Sui, Jinkai; Wang, Chunkai; Liu, Xiaofeng; Fang, Ning; Liu, Yanhua; Wang, Wenjing; Yan, Ning; Zhang, Huai-Bao; Du, Yongmei; Liu, Xinmin; Lu, Tiegang; Zhang, Zhongfeng; Zhang, Hongbo;
null
Chinese Acad Agr Sci, Biotechnol Res Inst, Beijing 100081, Peoples R China;Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China
Chinese Acad Agr Sci, Biotechnol Res Inst, Beijing 100081, Peoples R China;Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China
1420-3049
cembratriene-diol;COI1;jasmonate;secondary metabolism;tobacco
10
1954;1996;1998;2000;2001;2002;2003;2004;2006;2007;2008;2009;2010;2011;2012;2013;2014;2016;2017;2018
13
Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China
Molecules
Zhang, Hongbo
MDPI
(i.e.;(JA);(tobacco);,;a;acid;activities;addiction;also;although;and;anti-nicotine;are;been;bHLH;bioactive;by;catalyzing;CBTS;cembranoid;cembranoids;cembratriene-diol;cembratriene-diols;cembratriene-diols';COI1;components;compounds;correlated;could;critical;cv;demonstrated;derivative;display;diterpenoid;downstream;dysfunction;either;encoding;enhance;enzymes;expression;factor;findings;formation;found;further;gene;genes;governing;great;group;has;have;importance;in;investigated;is;its;JA;JA-Ile);JA-signaling;jasmonic;mechanism;modulate;molecular;MYB;MYB305;MYC2a;N.;natural;neuron;Nicotiana;NtLTP1;of;or;over-expressing;P450;pharmaceutical;physiological;phytohormone;plants;potentials;process;produced;production;protection;protein;receptor;regulating;regulators;regulatory;remains;reveal;role;roles;secretion;showed;species;studies;study;suggest;synthesis;synthetic;tabacum;taken;that;the;this;TN90;to;tobacco;together;transcription;trichome;underlying;unknown;upregulate;which;with
Chinese Acad Agr Sci
Cembranoids are a group of natural diterpenoid compounds with pharmaceutical potentials, and the cembratriene-diols produced by Nicotiana (tobacco) species display activities in anti-nicotine addiction and neuron protection. Although the enzymes catalyzing cembratriene-diols' formation in tobacco have been investigated, the regulatory mechanism underlying this physiological process remains unknown. This study has investigated the roles of phytohormone jasmonic acid (JA) in regulating cembratriene-diol formation in N. tabacum cv. TN90 and found that JA and COI1, the receptor protein of the bioactive derivative of JA (i.e., JA-Ile), display critical roles in regulating cembratriene-diols' formation and the expression of cembranoid synthetic genes CBTS, P450 and NtLTP1. Further studies showed that over-expressing either the gene encoding bHLH transcription factor MYC2a or that encoding MYB transcription factor MYB305 could upregulate the cembranoid synthetic genes and enhance the cembranoid production in plants with dysfunction of COI1. Further studies suggest that COI1 and its downstream regulators MYC2a and MYB305 also modulate the trichome secretion, which is correlated with cembranoid formation. Taken together, this study has demonstrated a critical role of JA-signaling components in governing the cembratriene-diol formation and the transcription of cembratriene-diol synthetic genes in tobacco. Findings in this study are of great importance to reveal the molecular regulatory mechanism underlying cembranoid synthesis.
AAU-8450-2021;HCI-5542-2022;HGV-1365-2022;IAN-4886-2023;ISU-3780-2023;IXX-1604-2023
ARABIDOPSIS;BIOSYNTHESIS;COI1;DEFENSE RESPONSES;DOMAIN PROTEINS INTERACT;GLANDULAR TRICHOMES;METABOLISM;MYC2;PLANT STRESS-RESPONSE;TRICHOME INITIATION
3
null
cembratriene-diol;COI1;jasmonate;secondary metabolism;tobacco
14
ARABIDOPSIS;BIOSYNTHESIS;cembratriene-diol;COI1;DEFENSE RESPONSE;DOMAIN PROTEINS INTERACT;GLANDULAR TRICHOMES;jasmonate;METABOLISM;MYC2;PLANT STRESS-RESPONSE;secondary metabolism;tobacco;TRICHOME INITIATION
WOS:000451201400107
Chinese Acad Agr Sci, Beijing, Peoples R China;Chinese Acad Agr Sci, Qingdao, Peoples R China
China
2,018
null
0000-0002-4541-5803;0000-0003-4035-8552
null
null
English
null
ANN BOT-LONDON;BIOCHEM J;BIOORGAN MED CHEM;CELL REP;CURR OPIN PLANT BIOL;DEVELOPMENT;GENE DEV;GENETICS;IND CROP PROD;J EXP BOT;J PLANT INTERACT;MOL PLANT;NAT BIOTECHNOL;NAT COMMUN;NAT PROTOC;NATURE;NEW PHYTOL;OECOLOGIA;P NATL ACAD SCI USA;PLANT CELL;PLANT CELL PHYSIOL;PLANT J;PLANT METHODS;PLANT MOL BIOL;PLANT PHYSIOL;PLANT SIGNAL BEHAV;PLANTA;SCIENCE;TRENDS PLANT SCI
Du, Yongmei;Fang, Ning;Liu, Xiaofeng;Liu, Xinmin;Liu, Yanhua;Lu, Tiegang;Sui, Jinkai;Wang, Chunkai;Wang, Wenjing;Yan, Ning;Zhang, Hongbo;Zhang, Huai-Bao;Zhang, Zhongfeng
2024-03-11 ER
An, L J;Boter, M;Brückner, K;Campos, M L;Chini, A;Choi, Y E;De Geyter, N;Devoto, A;Dombrecht, B;Graham, I A;Hailat, M M;Hong, G J;Huang, H;Huchelmann, A;Katsir, L;Kazan, K;Li, L;Lian, T F;Liu, G Y;Lorenzo, O;Ma, D C;Maes, L;Moyano, E;Payne, C T;Pesch, M;Qi, T C;Schilmiller, A L;Schmittgen, T D;Sheard, L B;Song, S S;Subramanian, C;Thines, B;Traw, M B;Turner, J G;Van Schie, C C N;Wang, E M;Wang, W J;Wasternack, C;Woldemariam, M G;Xie, D X;Yan, N;Yan, T X;Yemm, E W;Yoshida, Y;Zhang, H B;Zhang, H Y;Zhao, M;Zhu, Z Q
HB6SF
Qingdao, Peoples R China
15
null
1
null
30,274,345
Du, Yongmei;Fang, Ning;Liu, Xiaofeng;Liu, Xinmin;Liu, Yanhua;Lu, Tiegang;Sui, Jinkai;Wang, Chunkai;Wang, Wenjing;Yan, Ning;Zhang, Hongbo;Zhang, Huai-Bao;Zhang, Zhongfeng
MOLECULES
Beijing, Peoples R China;Qingdao, Peoples R China
Contreras-Llano, L E;Ding, Y F;Mao, M;Morris, E;Tan, C
10.1021/acsami.8b10029
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
6h2w261j21m6f3y6i2s163q612g2j36b4d6f4o
Minimizing Context Dependency of Gene Networks Using Artificial Cells
Univ Calif Davis
null
Tan, C (corresponding author), Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
null
Contreras-Llano, Luis E;Ding, Yunfeng;Mao, Michelle;Morris, Eliza;Tan, Cheemeng
Materials Science, Multidisciplinary;Nanoscience & Nanotechnology
Society-in-Science: Branco-Weiss Fellowship; NSF-CHE [1808237-0]; UC MEXUS-CONACYT Doctoral Fellowship; Direct For Mathematical & Physical Scien [1808237] Funding Source: National Science Foundation; Division Of Chemistry [1808237] Funding Source: National Science Foundation
WOS
Tan, C
Univ Calif Davis, Davis, CA USA
10
Artificial;Cells;Context;Dependency;gene;minimizing;networks;of;using
1
Llano, Luis Eduardo Contreras;Mao, Michelle;Morris, Eliza;Tan, Cheemeng
AMER CHEMICAL SOC
Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA
Article
Univ Calif Davis
WASHINGTON
null
null
Univ Calif Davis
Direct For Mathematical & Physical Scien;Division Of Chemistry;NSF-CHE;Society-in-Science: Branco-Weiss Fellowship;UC MEXUS-CONACYT Doctoral Fellowship
Tan, C (corresponding author), Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
30146
Contreras-Llano, Luis E;Ding, Yunfeng;Mao, Michelle;Morris, Eliza;Tan, Cheemeng
46
1
444,793,000,016
Direct For Mathematical & Physical Scien [1808237] Funding Source: National Science Foundation;Division Of Chemistry [1808237] Funding Source: National Science Foundation;NSF-CHE [1808237-0];Society-in-Science: Branco-Weiss Fellowship;UC MEXUS-CONACYT Doctoral Fellowship
USA
ACS APPLIED MATERIALS & INTERFACES
USA
null
null
Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA
1944-8244
Contreras-Llano, L E;Ding, Y F;Mao, M;Morris, E;Tan, C
SEP 12
cmtan@ucdavis.edu
Artificial Cells;Context Dependency;gene networks
5
J
Materials Science;Science & Technology - Other Topics
antimicrobial;artificial cells;BACTERIA;behavior;bioinspired mechanisms;biomimetics;biomolecules;CHEMICAL COMMUNICATION;chemical-context dependence;circuit;components;concentrations;Context Dependency;controlling robustness;designed functions;different chemical complexity;engineering;expression;extracellular chemical context;extracellular chemical contexts;FEEDBACK;functioning;gene networks;host cells;influences gene transcription;kill bacteria;liposomes;local chemical context;minimal dependency;molecular crowding;new frontier;persistent challenge;PROTOCELL;quorum sensing;ROBUSTNESS;sensitivity;simulated external environments;surrounding milieu;synthetic biological systems;synthetic biology;synthetic biomolecular compartments;synthetic gene circuits;synthetic gene networks;systems;translation;unknown cross talk;VESICLES
Ding, Y F
antimicrobial;artificial cells;BACTERIA;BEHAVIOR;biomimetics;CHEMICAL COMMUNICATION;CIRCUIT;EXPRESSION;FEEDBACK;molecular crowding;PROTOCELL;quorum sensing;ROBUSTNESS;Synthetic biology;synthetic gene circuits;SYSTEMS;VESICLES
30137
[Ding, Yunfeng; Contreras-Llano, Luis E.; Morris, Eliza; Mao, Michelle; Tan, Cheemeng] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
We thank Prof. Atul Parikh for sharing organic solvent and functional generator facilities. We appreciate the discussion of the manuscript with Prof. Philip LeDuc, Prof. Atul Parikh, Prof. Robert Smith, and Prof. Erkin Seker. This work is supported by Society-in-Science: Branco-Weiss Fellowship and NSF-CHE 1808237-0 to C.T. L.E.C.-L. is supported through a UC MEXUS-CONACYT Doctoral Fellowship.
artificial cells;bioinspired mechanisms;biomolecules;chemical-context dependence;components;concentrations;controlling robustness;designed functions;different chemical complexity;engineering;extracellular chemical context;extracellular chemical contexts;functioning;gene networks;host cells;influences gene transcription;kill bacteria;liposomes;local chemical context;minimal dependency;new frontier;persistent challenge;sensitivity;simulated external environments;surrounding milieu;synthetic biological systems;synthetic biology;synthetic biomolecular compartments;synthetic gene circuits;synthetic gene networks;translation;unknown cross talk
10.1002/adhm.201701163;10.1002/anie.201410139;10.1002/biot.201200085;10.1016/0005-2736(85)90521-8;10.1016/j.copbio.2016.02.032;10.1016/j.mattod.2016.02.020;10.1016/S0006-3495(99)77363-7;10.1021/acs.accounts.6b00512;10.1021/acscentsci.6b00330;10.1021/acssynbio.6b00198;10.1021/cb3006402;10.1038/35053176;10.1038/msb4100204;10.1038/nature07018;10.1038/nature09565;10.1038/nbt.2401;10.1038/nbt.3044;10.1038/nbt.4140;10.1038/nchembio.218;10.1038/ncomms5012;10.1038/ncomms6305;10.1038/nnano.2006.180;10.1038/nrd3028;10.1038/nrmicro1838;10.1039/c1cs15211d;10.1039/c3mb70032a;10.1039/c4cc02812k;10.1039/c5cs00361j;10.1039/c5ib00301f;10.1073/pnas.0408236101;10.1073/pnas.1001950107;10.1073/pnas.1300963110;10.1073/pnas.1316298111;10.1074/jbc.M104925200;10.1098/rsfs.2016.0011;10.1126/science.1192588;10.1128/AAC.43.5.1274;10.1146/annurev-biochem-080411-124036;10.1146/annurev.bi.43.070174.001125;[10.1038/NCHEM.1127, 10.1038/nchem.1127];[10.1038/NCHEM.1869, 10.1038/nchem.1869];[10.1038/NCHEM.2617, 10.1038/nchem.2617];[10.1038/NCHEM.2644, 10.1038/nchem.2644];[10.1038/nchem.296, 10.1038/NCHEM.296];[10.1038/NNANO.2013.132, 10.1038/nnano.2013.132];[10.1038/nnano.2013.309, 10.1038/NNANO.2013.309]
Univ Calif Davis
Contreras-Llano, L E;Ding, Y F;Mao, M;Morris, E;Tan, C
Ding, Y F: Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA
Contreras-Llano, Luis Eduardo;ding, yun;Llano, Luis Eduardo Contreras
1808237;1808237-0
46
null
USA
Univ Calif Davis
Ding, Yunfeng
null
BACTERIA;BEHAVIOR;CHEMICAL COMMUNICATION;CIRCUIT;EXPRESSION;FEEDBACK;PROTOCELL;SYNTHETIC BIOLOGY;SYSTEMS;VESICLES
Ding, Yunfeng; Contreras-Llano, Luis E.; Morris, Eliza; Mao, Michelle; Tan, Cheemeng;
null
Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA
Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA
null
antimicrobial;artificial cell;biomimetics;molecular crowding;quorum sensing;robustness;Synthetic gene circuit
36
1974;1985;1999;2001;2004;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
49
Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA
ACS Appl. Mater. Interfaces
Tan, Cheemeng
AMER CHEMICAL SOC
,;a;and;are;arises;artificial;bacteria;be;been;between;bioinspired;biological;biology;biomolecular;biomolecules;bottom-up;by;can;cells;challenge;chemical;chemical-context;circuits;compartments;complexity;components;concentrations;context;contexts;controlling;creates;cross;defined;dependence;dependency;depends;designed;detect;different;enables;encapsulate;engineered;engineering;environmental;environments;external;extracellular;factors;for;from;frontier;functioning;functions;gene;has;here;host;in;influences;interact;kill;liposomes;local;mechanisms;milieu;minimal;minimized;networks;new;of;on;our;persistent;rendered;robust;robustness;sensitivity;show;significant;simulated;surrounding;synthetic;systems;talk;that;the;their;this;to;transcription;translation;types;unknown;using;we;which;with;work;yet
Univ Calif Davis
The functioning of synthetic gene circuits depends on their local chemical context defined by the types and concentrations of biomolecules in the surrounding milieu that influences gene transcription and translation. This chemical-context dependence of synthetic gene circuits arises from significant yet unknown cross talk between engineered components, host cells, and environmental factors and has been a persistent challenge for synthetic biology. Here, we show that the sensitivity of synthetic gene networks to their extracellular chemical contexts can be minimized, and their designed functions rendered robust using artificial cells, which are synthetic biomolecular compartments engineered from the bottom-up using liposomes that encapsulate the gene networks. Our artificial cells detect, interact with, and kill bacteria in simulated external environments with different chemical complexity. Our work enables the engineering of synthetic gene networks with minimal dependency on their extracellular chemical context and creates a new frontier in controlling robustness of synthetic biological systems using bioinspired mechanisms.
HSB-4834-2023;P-6260-2018;P-8005-2019
BACTERIA;BEHAVIOR;CHEMICAL COMMUNICATION;CIRCUITS;EXPRESSION;FEEDBACK;PROTOCELLS;SYNTHETIC BIOLOGY;SYSTEM;VESICLES
3
null
antimicrobial;artificial cells;biomimetics;molecular crowding;quorum sensing;robustness;synthetic gene circuits
10
antimicrobial;artificial cell;BACTERIA;BEHAVIOR;biomimetics;CHEMICAL COMMUNICATION;CIRCUITS;EXPRESSION;FEEDBACK;molecular crowding;Protocells;quorum sensing;ROBUST;Synthetic biology;synthetic gene circuits;SYSTEM;VESICLES
WOS:000444793000016
Univ Calif Davis, Davis, CA USA
USA
2,018
null
0000-0001-9888-2520;0000-0002-4658-502X;0000-0002-9686-7375;0000-0003-1049-1192
null
null
English
null
ACCOUNTS CHEM RES;ACS CENTRAL SCI;ACS CHEM BIOL;ACS SYNTH BIOL;ADV HEALTHC MATER;ANGEW CHEM INT EDIT;ANNU REV BIOCHEM;ANTIMICROB AGENTS CH;BIOCHIM BIOPHYS ACTA;BIOPHYS J;BIOTECHNOL J;CHEM COMMUN;CHEM SOC REV;CURR OPIN BIOTECH;INTEGR BIOL-UK;INTERFACE FOCUS;J BIOL CHEM;MATER TODAY;MOL BIOSYST;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM;NAT CHEM BIOL;NAT COMMUN;NAT NANOTECHNOL;NAT REV DRUG DISCOV;NAT REV MICROBIOL;NATURE;P NATL ACAD SCI USA;SCIENCE
Contreras-Llano, Luis E;Ding, Yunfeng;Mao, Michelle;Morris, Eliza;Tan, Cheemeng
2024-03-11 ER
Adamala, K P;Black, R A;Blain, J C;Buddingh, B C;Cardinale, S;Chavez, M;Chou, L Y T;Cuatrecasas, P;Del Vecchio, D;Dzieciol, A J;Elani, Y;Gardner, P M;Giacomini, K M;Hope, M J;Hussain, F;Kobori, S;Kolmakov, G V;Krinsky, N;Kurihara, K;Leduc, P R;Lee, K Y;Lentini, R;Lou, C B;Mansy, S S;Martino, C;Mishra, D;Morris, E;Noireaux, V;Qiao, Y;Raffy, S;Schwarz-Schilling, M;Scott, M;Shong, J;Stewart, P S;Studart, A R;Szostak, J W;Tamsir, A;Tan, C;Tan, C M;Van Roekel, H W H;Walde, P;Weitz, M;Wu, M H;Xu, C;Zhang, L J
GT8NA
Davis, CA USA
52
null
1
null
30,113,814
Contreras-Llano, Luis E;Ding, Yunfeng;Mao, Michelle;Morris, Eliza;Tan, Cheemeng
ACS APPL MATER INTER
Davis, CA USA
Benzinger, D;Khammash, M
10.1038/s41467-018-05882-2
3521
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
5ia2g2x4t5r3l1s1m5o315h1v232x3s584s3f3x
Pulsatile inputs achieve tunable attenuation of gene expression variability and graded multi-gene regulation
Swiss Fed Inst Technol
null
Khammash, M (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland.
null
Benzinger, Dirk;Khammash, Mustafa
Multidisciplinary Sciences
European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [743269]
WOS
Khammash, M
Swiss Fed Inst Technol, Basel, Switzerland
9
achieve;and;attenuation;expression;gene;graded;inputs;multi-gene;of;pulsatile;regulation;tunable;variability
1
null
NATURE PUBLISHING GROUP
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland
Article
Swiss Fed Inst Technol
LONDON
null
null
Swiss Fed Inst Technol
European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme
Khammash, M (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland.
null
Benzinger, Dirk;Khammash, Mustafa
25
1
443,154,700,002
European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [743269]
Switzerland
NATURE COMMUNICATIONS
Switzerland
null
null
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland
2041-1723
Benzinger, D;Khammash, M
AUG 30
mustafa.khammash@bsse.ethz.ch
gene expression variability;graded multi-gene regulation;pulsatile inputs;tunable attenuation
2
J
Science & Technology - Other Topics
activation;beneficial functional behaviors;cell-to-cell variability;dynamic pulsatile signals;dynamic regulation;encoding;expression mean;fast-acting;fixed expression ratios;gene expression;gene expression variability;genetic parts;graded multi-gene regulation;lead;light;light-responsive promoter library;natural transcription factors;noise;optogenetic transcription factor;promoter dose-response characteristics;PROTEIN;pulsatile fashion;pulsatile inputs;pulsatile regulation;pulsatile signaling;REAL-TIME;required laborious optimization;Saccharomyces cerevisiae;SACCHAROMYCES-CEREVISIAE;signals;single input;SINGLE-CELL;synthetic biological systems;synthetic biology;synthetic gene expression systems;synthetic gene networks;SYSTEM;tunable attenuation;tuned;unknown;variability;yeast
Benzinger, D
ACTIVATION;LIGHT;NOISE;PROTEIN;REAL-TIME;SACCHAROMYCES-CEREVISIAE;SINGLE-CELL;Synthetic biology;SYSTEM;YEAST
null
[Benzinger, Dirk; Khammash, Mustafa] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland.
We thank for Peter Buchmann and Marc Rullan for the construction of and help with the LED-setup, Verena Jaggin for assistance with FACS, and Jan Mikelson for providing software for stochastic simulations. We thank members of the Khammash lab, Serge Pelet, and Martin Ackermann for helpful discussion and Stephanie Aoki for critical reading of the manuscript. We would further like to thank Fabian Rudolf (ETH Zurich), Kevin Gardner (City University of New York), Robert H Singer (Albert Einstein College of Medicine), and Daniel Zenklusen (Universite de Montreal) for providing plasmids. D. B. is part of the Life Science Zurich graduate school. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme grant agreement no. 743269 (CyberGenetics project).
beneficial functional behaviors;cell-to-cell variability;dynamic pulsatile signals;dynamic regulation;encoding;expression mean;fast-acting;fixed expression ratios;gene expression;genetic parts;graded multi-gene regulation;lead;light-responsive promoter library;natural transcription factors;optogenetic transcription factor;promoter dose-response characteristics;pulsatile fashion;pulsatile regulation;pulsatile signaling;required laborious optimization;Saccharomyces cerevisiae;signals;single input;synthetic biological systems;synthetic gene expression systems;synthetic gene networks;tuned;unknown;variability
10.1002/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO;2-U;10.1002/yea.3144;10.1002/yea.3152;10.1016/j.cell.2008.09.050;10.1016/j.celrep.2015.07.035;10.1016/j.jmb.2013.07.036;10.1016/j.mib.2016.07.009;10.1016/j.molcel.2006.11.003;10.1016/j.molcel.2018.04.012;10.1016/j.tibtech.2014.10.002;10.1016/S0031-3203(01)00127-3;10.1021/acssynbio.6b00072;10.1021/acssynbio.6b00251;10.1021/bi200976a;10.1021/j100540a008;10.1021/sb4000564;10.1038/335563a0;10.1038/35014651;10.1038/msb.2013.56;10.1038/nature01546;10.1038/nature04281;10.1038/nature07292;10.1038/nature26141;10.1038/nbt734;10.1038/nchembio.1753;10.1038/NMETH.1253;10.1038/NMETH.1524;10.1038/nmeth.2879;10.1038/nmeth1008;10.1038/s41467-017-01498-0;10.1042/BJ20081949;10.1073/pnas.0504604102;10.1073/pnas.0802601105;10.1073/pnas.0809901106;10.1074/jbc.M102815200;10.1088/0953-8984/23/15/153102;10.1093/nar/gkq091;10.1093/nar/gks1293;10.1093/nar/gks549;10.1093/nar/gku616;10.1103/PhysRevLett.108.108104;10.1126/science.1070919;10.1126/science.1098641;10.1126/science.1109090;10.1126/science.1202142;10.1126/science.1239999;10.1128/MMBR.00025-07;10.1186/1471-2105-10-106;10.3791/50382];10.7554/eLife.06559;[10.1038/nchembio.1337, 10.1038/NCHEMBIO.1337];[10.1038/NCHEMBIO.1430, 10.1038/nchembio.1430];[10.1038/NMETH.2075, 10.1038/nmeth.2075];[10.1038/NMETH.2794, 10.1038/nmeth.2794]
Swiss Fed Inst Technol
Benzinger, D;Khammash, M
Benzinger, D: Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland
null
743269
57
null
Switzerland
Swiss Fed Inst Technol
Benzinger, Dirk
Green Submitted, Green Published, gold
ACTIVATION;LIGHT;NOISE;PROTEIN;REAL-TIME;SACCHAROMYCES-CEREVISIAE;SINGLE-CELL;SYNTHETIC BIOLOGY;SYSTEM;YEAST
Benzinger, Dirk; Khammash, Mustafa;
null
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland
null
null
null
1977;1988;1989;1998;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
58
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, Mattenstr 26, CH-4058 Basel, Switzerland
Nat. Commun.
Khammash, Mustafa
NATURE PUBLISHING GROUP
,;a;also;and;are;at;be;behaviors;beneficial;benefit;biological;but;by;can;cell-to-cell;cerevisiae;characteristics;construct;construction;demonstrate;despite;differences;dose-response;dynamic;enables;encoding;expression;factor;factors;fashion;fast-acting;find;fixed;from;functional;further;gene;genetic;graded;here;how;in;independently;input;into;it;laborious;lead;library;light-responsive;many;mean;multi-gene;natural;networks;of;optimization;optogenetic;or;parts;previously;promoter;pulsatile;ratios;reduce;regulated;regulation;remains;required;Saccharomyces;show;signaling;signals;single;such;synthetic;systems;that;the;then;thus;to;transcription;tuned;unknown;using;variability;we;whether;which
Swiss Fed Inst Technol
Many natural transcription factors are regulated in a pulsatile fashion, but it remains unknown whether synthetic gene expression systems can benefit from such dynamic regulation. Here we find, using a fast-acting, optogenetic transcription factor in Saccharomyces cerevisiae, that dynamic pulsatile signals reduce cell-to-cell variability in gene expression. We then show that by encoding such signals into a single input, expression mean and variability can be independently tuned. Further, we construct a light-responsive promoter library and demonstrate how pulsatile signaling also enables graded multi-gene regulation at fixed expression ratios, despite differences in promoter dose-response characteristics. Pulsatile regulation can thus lead to beneficial functional behaviors in synthetic biological systems, which previously required laborious optimization of genetic parts or the construction of synthetic gene networks.
null
ACTIVATION;LIGHT;NOISE;PROTEIN;REAL-TIME;SACCHAROMYCES-CEREVISIAE;SINGLE-CELL;SYNTHETIC BIOLOGY;SYSTEM;YEAST
7
null
null
10
SACCHAROMYCES-CEREVISIAE;YEAST;ACTIVATION;LIGHT;NOISE;PROTEIN;REAL-TIME;SINGLE-CELL;Synthetic biology;SYSTEM
WOS:000443154700002
Swiss Fed Inst Technol, Basel, Switzerland
Switzerland
2,018
null
null
null
null
English
null
ACS SYNTH BIOL;BIOCHEM J;BIOCHEMISTRY-US;BMC BIOINFORMATICS;CELL;CELL REP;CURR OPIN MICROBIOL;ELIFE;GENETICS;J BIOL CHEM;J MOL BIOL;J PHYS CHEM-US;J PHYS-CONDENS MAT;JOVE-J VIS EXP;METHOD ENZYMOL;MICROBIOL MOL BIOL R;MOL CELL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PATTERN RECOGN;PHYS REV LETT;SCIENCE;TRENDS BIOTECHNOL;YEAST
Benzinger, Dirk;Khammash, Mustafa
2024-03-11 ER
Alper, H;Ang, J;Aranda-Díaz, A;Becskei, A;Blake, W J;Boer, V M;Borkowski, O;Brachmann, C B;Cai, L;Davidson, E A;De Chaumont, F;Delvigne, F;Du, J;Elowitz, M B;Fallahi-Sichani, M;Gietz, R D;Gillespie, D T;Gnügge, R;Gordon, A;Griesbeck, O;Hahne, F;Hansen, A S;Hecht, A;Kennedy, M J;Larson, D R;Levine, J H;Liang, J;Liu, J;Longtine, M S;Lugagne, J B;Mcisaac R. S.;Motta-Mena, L B;Murphy, K F;Nevoigt, E;Nevozhay, D;Olivo-Marin, J C;Ottoz, D S M;Pedraza, J M;Polstein, L R;Raj, A;Raser, J M;Rullan, M;Sadowski, I;Shcherbo, D;Shimizu-Sato, S;Sikorski, R S;Tkacik, G;Tostevin, F;Volfson, D;Zechner, C;Zhao, E M;Zoltowski, B D;Zuleta, I A
GS0CZ
Basel, Switzerland
67
null
1
null
30,166,548
Benzinger, Dirk;Khammash, Mustafa
NAT COMMUN
Basel, Switzerland
Cunha, R C;de Lima, M;Fernandes, M H V;Finger, P F;Fischer, G;Hübner, S O;Vargas, G D
10.1590/1678-5150-PVB-5343
null
EMBRAPA-SAUDE ANIMAL, KM47 SEROPEDICA, 23851-970 RIO JANEIRO, BRAZIL
256i3j673r4w56411r1wg1p4a5j725r3s415s1o
Antigenic and immunogenic properties of the canine distemper virus nucleocapsid protein expressed in <i>Escherichia</i> <i>coli</i> employing codon optimized synthetic gene
Univ Fed Pelotas
null
Hübner, SO (corresponding author), Univ Fed Pelotas UFPel, Dept Vet Prevent, Campus Capao do Leao,Ave Eliseu Maciel S-N, BR-96900010 Capao Do Leao, RS, Brazil.
null
Cunha, Rodrigo C;de Lima, Marcelo;Fernandes, Maureen H, V;Finger, Paula F;Fischer, Geferson;Hubner, Silvia O;Vargas, Gilberto D'Avila
Veterinary Sciences
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
WOS
Hübner, S O
Univ Fed Pelotas UFPel, Capao Do Leao RS, Brazil
38
<i>coli</i>;<i>Escherichia</i>;and;antigenic;canine;codon;distemper;employing;expressed;gene;immunogenic;in;nucleocapsid;of;optimized;properties;protein;synthetic;the;virus
1
Cunha, Rodrigo Casquero
REVISTA PESQUISA VETERINARIA BRASILEIRA
Univ Fed Pelotas UFPel, Ctr Desenvolvimento Tecnol, Biotecnol, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil;Univ Fed Pelotas UFPel, Dept Vet Prevent, Campus Capao do Leao,Ave Eliseu Maciel S-N, BR-96900010 Capao Do Leao, RS, Brazil;Univ Fed Pelotas UFPel, Programa Posgrad Med Vet, Fac Vet, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil
Article
Univ Fed Pelotas
RIO JANEIRO
null
null
Brazil;Univ Fed Pelotas UFPel
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES);Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
Hübner, SO (corresponding author), Univ Fed Pelotas UFPel, Dept Vet Prevent, Campus Capao do Leao,Ave Eliseu Maciel S-N, BR-96900010 Capao Do Leao, RS, Brazil.
1621
Cunha, Rodrigo C;de Lima, Marcelo;Fernandes, Maureen H, V;Finger, Paula F;Fischer, Geferson;Hubner, Silvia O;Vargas, Gilberto D'Avila
1
3
448,939,600,020
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES);Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
Brazil
PESQUISA VETERINARIA BRASILEIRA
Brazil
null
null
Univ Fed Pelotas UFPel, Programa Posgrad Med Vet, Fac Vet, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil
0100-736X
Cunha, R C;de Lima, M;Fernandes, M H V;Finger, P F;Fischer, G;Hübner, S O;Vargas, G D
AUG
silviaohubner@yahoo.com.br
<i>Escherichia</i> <i>coli</i>;canine distemper virus nucleocapsid protein;codon;immunogenic properties;synthetic gene
7
J
Veterinary Sciences
28.55mg/mL;<i>Escherichia</i> <i>coli</i>;antigenic;Brazil;canine distemper disease;canine distemper immunodiagnostic assays;canine distemper virus;canine distemper virus (rCDV NP);canine distemper virus nucleocapsid protein;CDV;CDV positive dog sera;CHICKEN IGY;codon;common occurrence;conserved region;development;Diagnosis;Dogs;egg yolk;EGG-YOLK;ELISA;ELISA assays;Escherichia coli;expression;findings;hens;high concentration;His-Tag monoclonal antibodies;IgY;immunogenic;immunogenic characteristics;immunogenic properties;immunoglobulin Y (IgY);importance;infection;LINKED-IMMUNOSORBENT-ASSAY;low sensitivity;majority;mean yield;MONOCLONAL-ANTIBODY;negative control dog sera;NP;nucleocapsid protein;NUCLEOPROTEIN;positive;PROTEIN;purified);rCDVNP;rCDVNP antigenicity;recombinant protein;REGION;results;SDS-PAGE;specific IgY;specific IgY antibodies;specificity;Star strain (mean 300 mu g/mL;study;summary;synthetic gene;taken;useful tools;viroses;vitro;western blot;Western blot analysis
Fernandes, M H V
antigenic;BRAZIL;canine distemper virus;CDV;CHICKEN IGY;codon;Dogs;EGG-YOLK;ELISA;Escherichia coli;EXPRESSION;IgY;immunogenic;INFECTION;LINKED-IMMUNOSORBENT-ASSAY;MONOCLONAL-ANTIBODY;NP;nucleocapsid protein;NUCLEOPROTEIN;REGION;Synthetic gene;viroses
1615
[Fernandes, Maureen H., V; Finger, Paula F.] Univ Fed Pelotas UFPel, Programa Posgrad Med Vet, Fac Vet, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil. [Cunha, Rodrigo C.] Univ Fed Pelotas UFPel, Ctr Desenvolvimento Tecnol, Biotecnol, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil. [Vargas, Gilberto D'Avila; Fischer, Geferson; de Lima, Marcelo; Hubner, Silvia O.] Univ Fed Pelotas UFPel, Dept Vet Prevent, Campus Capao do Leao,Ave Eliseu Maciel S-N, BR-96900010 Capao Do Leao, RS, Brazil.
Financial support was provided by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq).
28.55mg/mL;canine distemper disease;canine distemper immunodiagnostic assays;canine distemper virus (rCDV NP);CDV positive dog sera;codon;common occurrence;conserved region;development;diagnosis;egg yolk;ELISA;ELISA assays;Escherichia coli;expression;findings;hens;high concentration;His-Tag monoclonal antibodies;IgY;immunogenic;immunogenic characteristics;immunoglobulin Y (IgY);importance;low sensitivity;majority;mean yield;negative control dog sera;nucleocapsid protein;positive;protein;purified);rCDVNP;rCDVNP antigenicity;recombinant protein;results;SDS-PAGE;specific IgY;specific IgY antibodies;specificity;Star strain (mean 300 mu g/mL;study;summary;synthetic gene;taken;useful tools;vitro;western blot;Western blot analysis
10.1002/0471140864.ps0501s00;10.1016/0378-1135(95)00014-2;10.1016/j.antiviral.2011.11.005;10.1016/j.cvsm.2008.02.007;10.1016/j.intimp.2014.01.026;10.1016/j.jviromet.2006.05.004;10.1016/j.jviromet.2008.05.023;10.1016/j.jviromet.2008.09.024;10.1016/j.jviromet.2009.07.014;10.1016/j.jviromet.2014.12.004;10.1016/j.pep.2013.10.016;10.1016/j.trstmh.2009.10.005;10.1016/j.vaccine.2007.02.053;10.1016/j.vetimm.2007.06.006;10.1016/j.vetimm.2008.09.023;10.1016/j.vetmic.2006.11.019;10.1016/S0378-1135(97)00194-6;10.1038/emi.2015.26;10.1046/j.1439-0442.1999.00198.x;10.1079/WPS200422;10.1080/09168451.2016.1217144;10.1089/mab.2013.0066;10.1093/bib/5.4.378;10.1093/bioinformatics/bts199;10.1099/0022-1317-78-2-373;10.1101/PDB.PR0T3944;10.1111/j.1365-2621.1992.tb08058.x;10.1111/j.1439-0450.1989.tb00659.x;10.1128/JCM.37.11.3634-3643.1999;10.1128/JCM.37.4.1049-1056.1999;10.1292/jvms.59.51;10.1371/journal.pone.0007002;10.1586/ERM.10.61;10.1590/S0100-736X2008000400005;10.1590/S0100-879X2004000800001;10.1590/S0103-84782007000400016;10.1638/1042-7260(2000)031[0441:CDITCA]2.0.CO;2;10.3109/08820138009066010;10.3791/253;10.4142/jvs.2014.15.4.503;10.4142/jvs.2016.17.3.307
Univ Fed Pelotas UFPel
Cunha, R C;de Lima, M;Fernandes, M H V;Finger, P F;Fischer, G;Hübner, S O;Vargas, G D
Fernandes, M H V: Univ Fed Pelotas UFPel, Programa Posgrad Med Vet, Fac Vet, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil
Cunha, Rodrigo Casquero;Lima, Marcelo
null
45
null
Brazil
Univ Fed Pelotas UFPel
Fernandes, Maureen H, V
Green Published, gold
BRAZIL;CHICKEN IGY;DOGS;EGG-YOLK;ELISA;INFECTION;LINKED-IMMUNOSORBENT-ASSAY;MONOCLONAL-ANTIBODY;NUCLEOPROTEIN;REGION
Fernandes, Maureen H., V; Finger, Paula F.; Cunha, Rodrigo C.; Vargas, Gilberto D'Avila; Fischer, Geferson; de Lima, Marcelo; Hubner, Silvia O.;
null
Univ Fed Pelotas UFPel, Ctr Desenvolvimento Tecnol, Biotecnol, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil;Univ Fed Pelotas UFPel, Dept Vet Prevent, Campus Capao do Leao,Ave Eliseu Maciel S-N, BR-96900010 Capao Do Leao, RS, Brazil;Univ Fed Pelotas UFPel, Programa Posgrad Med Vet, Fac Vet, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil
Univ Fed Pelotas UFPel, Ctr Desenvolvimento Tecnol, Biotecnol, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil;Univ Fed Pelotas UFPel, Dept Vet Prevent, Campus Capao do Leao,Ave Eliseu Maciel S-N, BR-96900010 Capao Do Leao, RS, Brazil;Univ Fed Pelotas UFPel, Programa Posgrad Med Vet, Fac Vet, Campus Capao do Leao, BR-96900010 Capao Do Leao, RS, Brazil
1678-5150
Escherichia coli;Antigenicity;canine distemper virus;CDV;codon;DOG;expression;IgY;immunogenicity;NP;nucleocapsid protein;Synthetic gene;viroses
8
1980;1989;1992;1995;1997;1998;1999;2000;2001;2004;2006;2007;2008;2009;2010;2012;2014;2015;2016
0
Univ Fed Pelotas UFPel, Dept Vet Prevent, Campus Capao do Leao,Ave Eliseu Maciel S-N, BR-96900010 Capao Do Leao, RS, Brazil
Pesqui. Vet. Bras.
Hubner, Silvia O
REVISTA PESQUISA VETERINARIA BRASILEIRA
(IgY);(mean;(rCDV;,;28.55mg/mL;300;a;additionally;along;analysis;and;antibodies;antigenic;antigenicity;are;as;assays;available;be;being;blot;by;canine;CDV;characteristics;codon;coli;common;concentration;confirmed;conserved;control;could;currently;demonstrated;despite;development;diagnosis;disease;distemper;dog;egg;either;ELISA;employing;Escherichia;evaluated;expressed;expression;findings;for;from;g/mL;gene;hampered;hens;high;His-Tag;IgY;immunodiagnostic;immunogenic;immunoglobulin;importance;in;indicate;inoculated;is;isolate;it;low;majority;mean;monoclonal;mu;negative;NP);nucleocapsid;occurrence;of;optimized;or;our;positive;possible;protein;proved;purified;purified);rCDVNP;reacted;recognized;recombinant;region;results;SDS-PAGE;sensitivity;sera;since;specific;specificity;Star;strain;study;summary;synthetic;taken;tests;that;the;these;this;to;together;tools;useful;using;virus;vitro;was;Western;with;Y;yield;yolk
Univ Fed Pelotas UFPel
Despite common occurrence and importance of canine distemper disease the majority of tests currently available for diagnosis are hampered by either low sensitivity or specificity. In this study it was evaluated antigenic and immunogenic characteristics of a conserved region of nucleocapsid protein of canine distemper virus (rCDV NP) expressed in Escherichia coli employing a codon optimized synthetic gene. The expression of rCDVNP in Star strain (mean 300 mu g/mL, purified) was confirmed by SDS-PAGE and Western blot analysis by using His-Tag monoclonal antibodies. Western blot and ELISA, employing positive and negative control dog sera, demonstrated the rCDVNP antigenicity. The rCDVNP was inoculated in hens and immunoglobulin Y (IgY) was purified from the egg yolk. The mean yield of IgY was 28.55mg/mL. IgY reacted with the recombinant protein as demonstrated by Western blot and ELISA assays. In summary, our findings demonstrated that rCDVNP is antigenic since CDV positive dog sera recognized the protein in vitro. Additionally, the rCDVNP proved to be immunogenic in hens being possible to isolate a high concentration of specific IgY antibodies from the egg yolk. Taken together, these results indicate that the rCDVNP along with the specific IgY could be useful tools for development of the canine distemper immunodiagnostic assays.
AAJ-4965-2021;AFZ-3898-2022
BRAZIL;CHICKEN IGY;DOGS;EGG-YOLK;ELISA;INFECTION;LINKED-IMMUNOSORBENT-ASSAY;MONOCLONAL-ANTIBODIES;NUCLEOPROTEIN;REGION
0
null
antigenic;canine distemper virus;CDV;codon;Dogs;Escherichia coli;expression;IgY;immunogenic;NP;nucleocapsid protein;Synthetic gene;viroses
7
ESCHERICHIA-COLI;ANTIGEN;BRAZIL;canine distemper virus;CDV;CHICKEN IGY;codon;Dogs;EGG-YOLK;ELISA;EXPRESSION;IgY;IMMUNOGENICITY;INFECTION;LINKED-IMMUNOSORBENT-ASSAY;MONOCLONAL-ANTIBODIES;NP;nucleocapsid protein;NUCLEOPROTEIN;REGION;Synthetic gene;viroses
WOS:000448939600020
Univ Fed Pelotas UFPel, Capao Do Leao RS, Brazil
Brazil
2,018
null
0000-0003-0145-0321
null
null
English
null
ANTIVIR RES;BIOINFORMATICS;BIOSCI BIOTECH BIOCH;BRAZ J MED BIOL RES;BRIEF BIOINFORM;CSH Protoc;Curr Protoc Protein Sci;EMERG MICROBES INFEC;Expert Rev Mol Diagn;Genome Synthesis and Design Futures;IMMUNOL COMMUN;INT COMM TAX VIR;INT IMMUNOPHARMACOL;J CLIN MICROBIOL;J FOOD SCI;J GEN VIROL;J VET MED A;J VET MED B;J VET MED SCI;J VET SCI;J VIROL METHODS;J Vis Exp;J ZOO WILDLIFE MED;Monoclonal Antibodies in Immunodiagnosis and Immunotherapy;NEW MICROBIOL;PESQUI VET BRASIL;PLOS ONE;PROTEIN EXPRES PURIF;REVTA CIENC MED BIOL;T ROY SOC TROP MED H;VACCINE;VET CLIN N AM-SMALL;VET IMMUNOL IMMUNOP;VET MICROBIOL;WORLD POULTRY SCI J
Cunha, Rodrigo C;de Lima, Marcelo;Fernandes, Maureen H, V;Finger, Paula F;Fischer, Geferson;Hubner, Silvia O;Vargas, Gilberto D'Avila
2024-03-11 ER
Akita, E M;Balamurugan, V;Barben, G;Beineke, A;Bentubo Henri Donnarumma Levy;Chan, K W;Chen, Y;Cho, K H;Deem, S L;Elia, G;Fighera, R A;Frisk, A L;Froger Alexandrine;Guimaraes M. C. C.;Ictv;Iwatsuki, K;Kammila, S;Karlsson, M;Kearse, M;Latha, D;Lavallie E, R;Lee, H;Li, G Q;Martella, V;Newcomb J.;Papaneophytou, C P;Polson, A;Ramos, C R R;Sambrook J.;Schmidt, P;Shin, Y S;Spencer, K A;Stettler, M;Vasconcellos, F A;Veerasami, M;Von Messling, V;Welch, M;Wen, J L;Yadav, V;Yi Li;Yoshida, E;Zhang, R H;Zhang, X Y
GY9DP
Capao Do Leao RS, Brazil
0
null
1
null
null
Cunha, Rodrigo C;de Lima, Marcelo;Fernandes, Maureen H, V;Finger, Paula F;Fischer, Geferson;Hubner, Silvia O;Vargas, Gilberto D'Avila
PESQUI VET BRASIL
Capao Do Leao RS, Brazil
Chen, G Y;Chen, Z Y;Jiang, Q T;Li, W;Li, Z;Pu, Z E;Wei, Y M;Zhao, X F;Zheng, Y L
10.1556/0806.46.2018.09
null
BUDAFOKI UT 187-189-A-3, H-1117 BUDAPEST, HUNGARY
5w2l716x654b1r521v2x3i293k126186c5c175z
Characterization of Starch Synthetic Genes and Starch Granule during Seeds Development between Synthetic Hexaploid Wheat and its Parents
Sichuan Agr Univ
null
Zheng, YL (corresponding author), Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China.
null
Chen, G Y;Chen, Z Y;Jiang, Q T;Li, W;Li, Z;Pu, Z E;Wei, Y M;Zhao, X F;Zheng, Y L
Agronomy
Key Project of National Natural Science Foundation of China [31230053]; International Science & Technology Cooperation Program of China [2015DFA30600]
WOS
Zheng, Y L
Sichuan Agr Univ, Sichuan, Peoples R China
46
and;between;characterization;Development;during;genes;Granule;Hexaploid;its;of;Parents;Seeds;Starch;synthetic;Wheat
1
null
AKADEMIAI KIADO ZRT
Sichuan Agr Univ, Coll Agron, Chengdu 611130, Sichuan, Peoples R China;Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China
Article
Sichuan Agr Univ
BUDAPEST
null
null
Sichuan Agr Univ
International Science & Technology Cooperation Program of China;Key Project of National Natural Science Foundation of China
Zheng, YL (corresponding author), Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China.
286
Chen, G Y;Chen, Z Y;Jiang, Q T;Li, W;Li, Z;Pu, Z E;Wei, Y M;Zhao, X F;Zheng, Y L
24
2
439,810,300,009
International Science & Technology Cooperation Program of China [2015DFA30600];Key Project of National Natural Science Foundation of China [31230053]
China
CEREAL RESEARCH COMMUNICATIONS
China
null
null
Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China
0133-3720
Chen, G Y;Chen, Z Y;Jiang, Q T;Li, W;Li, Z;Pu, Z E;Wei, Y M;Zhao, X F;Zheng, Y L
JUN
ylzheng@sicau.edu.cn
characterization;Parents;Seeds Development;Starch Granule;Starch Synthetic Genes;Synthetic Hexaploid Wheat
9
J
Agriculture
AEGILOPS;AGPLSU2;AGPSSU1;AGPSSU2;amount;AS2255;AS60;B-type granule;biosynthesis;characterization;developed starch granules;development;diploid Ae;DURUM;earlier stages;electron microscopy (SEM);ENDOSPERM;expression;expression pattern;GBSSI;genes;grain weight;hexaploid wheat;higher starch content;important role;larger quantity;Parents;parents T. turgidum AS2255;pattern;PHO1;PHO2;plays;polyploid wheats;results;RT-qPCR result;seed;Seeds Development;SHW-L1;SSIII;starch content;starch granule;starch granule development;starch granules;starch quality improvement;starch synthase;starch synthase gene expression;starch synthase genes;Starch Synthetic Genes;starch synthetic genes AGPLSU1;SYNTHASE;synthetic hexaploid wheat;synthetic hexaploid wheat SHW-L1;T-TAUSCHII;tauschii AS60;tetraploid;tetraploid parent;tetraploid wheat;three genotypes;TRITICUM-TURGIDUM;variability;WAXY PROTEINS;wheat grain development
Li, W
AEGILOPS;BIOSYNTHESIS;DURUM;ENDOSPERM;EXPRESSION;seed;starch granule;starch synthase;SYNTHASE;synthetic hexaploid wheat;T-TAUSCHII;tetraploid;TRITICUM-TURGIDUM;VARIABILITY;WAXY PROTEINS
275
[Li, W.; Chen, Z. Y.; Li, Z.; Zhao, X. F.; Pu, Z. E.; Chen, G. Y.; Jiang, Q. T.; Wei, Y. M.; Zheng, Y. L.] Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China. [Li, W.; Chen, Z. Y.; Li, Z.; Zhao, X. F.; Pu, Z. E.] Sichuan Agr Univ, Coll Agron, Chengdu 611130, Sichuan, Peoples R China.
This work was supported by The Key Project of National Natural Science Foundation of China (No. 31230053) and The International Science & Technology Cooperation Program of China (No. 2015DFA30600).
AGPLSU2;AGPSSU1;AGPSSU2;amount;AS2255;AS60;B-type granule;developed starch granules;development;diploid Ae;earlier stages;electron microscopy (SEM);expression;expression pattern;GBSSI;genes;grain weight;hexaploid wheat;higher starch content;important role;larger quantity;parents;parents T. turgidum AS2255;pattern;PHO1;PHO2;plays;polyploid wheats;results;RT-qPCR result;SHW-L1;SSIII;starch content;starch granule development;starch granules;starch quality improvement;starch synthase gene expression;starch synthase genes;starch synthetic genes;starch synthetic genes AGPLSU1;synthetic hexaploid wheat;synthetic hexaploid wheat SHW-L1;tauschii AS60;tetraploid parent;tetraploid wheat;three genotypes;wheat grain development
10.1006/anbo.2001.1531;10.1007/BF00027057;10.1007/s10681-008-9864-5;10.1007/s10681-012-0850-6;10.1007/s10722-009-9424-4;10.1007/s10722-011-9787-1;10.1007/s10722-015-0296-5;10.1007/s10725-010-9450-4;10.1007/s11032-009-9314-7;10.1007/s11032-010-9493-2;10.1016/j.jcs.2009.12.002;10.1016/j.jcs.2013.01.001;10.1016/j.jplph.2009.05.004;10.1016/S0065-2296(05)40001-4;10.1016/S0168-9452(03)00076-1;10.1016/S0378-1119(99)00178-X;10.1016/S0733-5210(95)80004-2;10.1016/S1369-5266(03)00042-6;10.1023/A:1018345505142;10.1046/j.1365-313x.2001.01012.x;10.1046/j.1439-0523.2000.00448.x;10.1073/pnas.072223799;10.1093/jxb/erh248;10.1093/jxb/eri065;10.1093/nar/29.9.e45;10.1093/oxfordjournals.aob.a088332;10.1094/CCHEM-85-1-0051;10.1094/CCHEM.2003.80.2.175;10.1104/pp.010363;10.1104/pp.107.3.673;10.1104/pp.120.4.993;10.1105/tpc.10.3.399;10.1105/tpc.107.054007;10.1105/tpc.13.8.1735;10.1105/tpc.7.7.971;10.1111/j.1439-037X.1994.tb00578.x;10.1139/g95-135;10.1139/gen-41-2-272;10.1146/annurev.arplant.54.031902.134927;10.1186/1471-2229-12-147;10.1186/1756-0500-3-140;10.1360/03yc0177
Sichuan Agr Univ
Chen, G Y;Chen, Z Y;Jiang, Q T;Li, W;Li, Z;Pu, Z E;Wei, Y M;Zhao, X F;Zheng, Y L
Li, W: Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China
feng, chen;Jiang, Qiantao;Jiang, Tao;Li, Tao;sheng, chen;SUN, YANLING;Yang, Tian
2015DFA30600;31230053
43
null
China
Sichuan Agr Univ
Li, W
null
AEGILOPS;BIOSYNTHESIS;DURUM;ENDOSPERM;EXPRESSION;SYNTHASE;T-TAUSCHII;TRITICUM-TURGIDUM;VARIABILITY;WAXY PROTEINS
Li, W.; Chen, Z. Y.; Li, Z.; Zhao, X. F.; Pu, Z. E.; Chen, G. Y.; Jiang, Q. T.; Wei, Y. M.; Zheng, Y. L.;
null
Sichuan Agr Univ, Coll Agron, Chengdu 611130, Sichuan, Peoples R China;Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China
Sichuan Agr Univ, Coll Agron, Chengdu 611130, Sichuan, Peoples R China;Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China
1788-9170
seed;starch granule;starch synthase;synthetic hexaploid wheat;tetraploid
2
1992;1994;1995;1998;1999;2000;2001;2002;2003;2004;2005;2008;2009;2010;2011;2012;2013;2016
1
Sichuan Agr Univ, Triticeae Res Inst, Chengdu 611130, Sichuan, Peoples R China
Cereal Res. Commun.
Zheng, Y L
AKADEMIAI KIADO ZRT
(SEM);,;above;Ae;AGPLSU1;AGPLSU2;AGPSSU1;AGPSSU2;all;also;amount;and;AS2255;AS60;associated;at;B-type;between;content;could;developed;development;diploid;during;earlier;electron;expressed;expression;for;from;GBSSI;gene;genes;genotypes;grain;granule;granules;hexaploid;higher;important;improvement;in;inherited;investigated;its;larger;less;mentioned;microscopy;more;of;parent;parents;pattern;PHO1;PHO2;plays;polyploid;quality;quantity;rapidly;result;results;role;RT-qPCR;scanning;showed;SHW-L1;significantly;slower;SSIII;stages;starch;study;suggest;suggested;synthase;synthetic;T.;tauschii;tetraploid;than;that;the;three;to;turgidum;was;we;weight;wheat;wheats;with
Sichuan Agr Univ
To study the development of starch granules in polyploid wheats, we investigated the expression of starch synthetic genes between the synthetic hexaploid wheat SHW-L1, its parents T. turgidum AS2255 and diploid Ae. tauschii AS60. The synthetic hexaploid wheat SHW-L1 showed significantly higher starch content and grain weight than its parents. Scanning electron microscopy (SEM) showed that SHW-L1 rapidly developed starch granules than AS2255 and AS60. The amount of B-type granule in AS60 was less than that in SHW-L1 and AS2255. RT-qPCR result showed that the starch synthetic genes AGPLSU1, AGPLSU2, AGPSSU1, AGPSSU2, GBSSI, SSIII, PHO1 and PHO2 expressed at earlier stages with larger quantity in SHW-L1 than in its parents during wheat grain development. The expression of the above mentioned genes in AS60 was slower than in SHW-L1 and AS2255. The expression pattern of starch synthase genes was also associated with the grain weight and starch content in all three genotypes. The results suggested that the synthetic hexaploid wheat inherited the pattern of starch granule development and starch synthase gene expression from tetraploid parent. The results suggest that tetraploid wheat could plays more important role for starch quality improvement in hexaploid wheat.
C-6229-2017;IWM-7503-2023;IWU-9607-2023;JEO-8801-2023;JFB-1008-2023;JLM-8296-2023;JTT-9082-2023
AEGILOPS;BIOSYNTHESIS;DURUM;ENDOSPERM;EXPRESSION;SYNTHASE;T-TAUSCHII;TRITICUM-TURGIDUM;VARIABILITY;WAXY PROTEINS
4
null
seed;starch granule;starch synthase;synthetic hexaploid wheat;tetraploid
12
AEGILOPS;BIOSYNTHESIS;DURUM;ENDOSPERM;EXPRESSION;SEEDS;starch granule;starch synthase;SYNTHASE;synthetic hexaploid wheat;T-TAUSCHII;tetraploid;TRITICUM-TURGIDUM;VARIABILITY;WAXY PROTEINS
WOS:000439810300009
Sichuan Agr Univ, Sichuan, Peoples R China
China
2,018
null
null
null
null
English
null
ADV BOT RES;ANN BOT-LONDON;ANNU REV PLANT BIOL;BMC PLANT BIOL;BMC Res Notes;CEREAL CHEM;CURR OPIN PLANT BIOL;EUPHYTICA;GENE;GENET RESOUR CROP EV;GENOME;J AGRON CROP SCI;J CEREAL SCI;J EXP BOT;J PLANT PHYSIOL;MOL BREEDING;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLANT BREEDING;PLANT CELL;PLANT GROWTH REGUL;PLANT J;PLANT PHYSIOL;PLANT SCI;SCI CHINA SER C
Chen, G Y;Chen, Z Y;Jiang, Q T;Li, W;Li, Z;Pu, Z E;Wei, Y M;Zhao, X F;Zheng, Y L
2024-03-11 ER
Ball, S G;Bechtel, D B;Burton, R A;Colleoni, C;Critchley, J H;Dian, W M;Flood, R G;Gao, M;Gororo, N N;Guo, G F;Guzmán, C;Hogg, A C;Huang Xiu-Qiang;Huang, S;Hurkman, W J;James, M G;Kang, G Z;Konik-Rose, C M;Li Zhongyi;Li, W;Limin, A E;Liu, B;Ma, H;Martin, C;Murai, J;Nieto-Taladriz, M T;Ozkan, H;Pena, R J;Pfaffl, M W;Satoh, H;Sestili, F;Smith, A M;Tetlow, I J;Tickle, P;Tomlinson, K;Villareal, R L;Watanabe, N;Yamamori, M;Zhang, C H;Zhang, L Q;Zhu, T
GO2NI
Sichuan, Peoples R China
1
null
1
null
null
Chen, G Y;Chen, Z Y;Jiang, Q T;Li, W;Li, Z;Pu, Z E;Wei, Y M;Zhao, X F;Zheng, Y L
CEREAL RES COMMUN
Sichuan, Peoples R China
Aubel, D;Fussenegger, M;Sedlmayer, F
10.1038/s41551-018-0215-0
null
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
6p6w215z3j32n1b5j6p2z155f5l1i4o5m4ua2
Synthetic gene circuits for the detection, elimination and prevention of disease
Swiss Fed Inst Technol
null
Fussenegger, M (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.;Fussenegger, M (corresponding author), Univ Basel, Fac Sci, Basel, Switzerland.
null
Aubel, Dominique;Fussenegger, Martin;Sedlmayer, Ferdinand
Engineering, Biomedical
European Research Council Advanced Grant (ProNet) [321381]; European Research Council (ERC) [321381] Funding Source: European Research Council (ERC)
WOS
Fussenegger, M
Swiss Fed Inst Technol, Basel, Switzerland;Univ Basel, Basel, Switzerland;Univ Claude Bernard Lyon, Lyon, France
2
,;and;circuits;detection;disease;elimination;for;gene;of;prevention;synthetic;the
2
Sedlmayer, Ferdinand
NATURE PUBLISHING GROUP
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland;Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.; Fussenegger, M (corresponding author), Univ Basel, Fac Sci, Basel, Switzerland;Univ Basel, Fac Sci, Basel, Switzerland;Univ Claude Bernard Lyon 1, IUTA Dept Genie Biol, Lyon, France
Review
Swiss Fed Inst Technol;Univ Basel
LONDON
null
null
Swiss Fed Inst Technol;Univ Basel;Univ Claude Bernard Lyon 1
European Research Council (ERC);European Research Council Advanced Grant (ProNet)
Fussenegger, M (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.; Fussenegger, M (corresponding author), Univ Basel, Fac Sci, Basel, Switzerland.
415
Aubel, Dominique;Fussenegger, Martin;Sedlmayer, Ferdinand
146
3
435,474,500,010
European Research Council (ERC) [321381] Funding Source: European Research Council (ERC);European Research Council Advanced Grant (ProNet) [321381]
France;Switzerland
NATURE BIOMEDICAL ENGINEERING
Switzerland
null
null
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
2157-846X
Aubel, D;Fussenegger, M;Sedlmayer, F
JUN
fussenegger@bsse.ethz.ch
detection;disease;elimination;prevention;synthetic gene circuits
3
J
Engineering
applications;autoimmune diseases;AUTOMATED DESIGN;autonomously;basis;BIOLOGY;biomedical applications;cancer remission;changing conditions;clinic;controlled timing;CONTROLLED TRANSGENE EXPRESSION;DELIVERY;DESIGNER CELLS;designing molecular building blocks de novo;detection;devices;diagnostics;disease;disease biomarkers;dosage;elimination;ENGINEERED BACTERIA;experimental animal models;first;human cells;inspired biologists;laboratory;leap;living organisms;major disease areas;MAMMALIAN-CELLS;monitor;natural processes;network's unprecedented specificity;ORGANISMS;pathways;prevention;process environmental cues trigger corrective actions;production;proteins;repurposing;review;RNA;Sensors;synthetic gene circuits;synthetic living sensors;synthetic-biology principles;T-CELLS;tailored genetic networks;therapeutics;TRANSCRIPTIONAL ACTIVATION;unbalanced pathological states;user-defined synthetic gene circuits
Sedlmayer, F
AUTOMATED DESIGN;BIOLOGY;CONTROLLED TRANSGENE EXPRESSION;DELIVERY;DESIGNER CELLS;ENGINEERED BACTERIA;MAMMALIAN-CELLS;RNA;T-CELLS;TRANSCRIPTIONAL ACTIVATION
399
[Sedlmayer, Ferdinand; Fussenegger, Martin] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland. [Aubel, Dominique] Univ Claude Bernard Lyon 1, IUTA Dept Genie Biol, Lyon, France. [Fussenegger, Martin] Univ Basel, Fac Sci, Basel, Switzerland.
We thank D. Fuchs, D. Sequeira, X. Pierrat and S. Auslander for scientific advice. This work was supported by a European Research Council Advanced Grant (ProNet, no. 321381).
applications;autoimmune diseases;autonomously;basis;biomedical applications;cancer remission;changing conditions;clinic;controlled timing;designer cells;designing molecular building blocks de novo;devices;diagnostics;disease biomarkers;dosage;experimental animal models;first;human cells;inspired biologists;laboratory;leap;living organisms;major disease areas;monitor;natural processes;network's unprecedented specificity;organisms;pathways;process environmental cues trigger corrective actions;production;proteins;repurposing;review;sensors;synthetic gene circuits;synthetic living sensors;synthetic-biology principles;tailored genetic networks;therapeutics;unbalanced pathological states;user-defined synthetic gene circuits
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Swiss Fed Inst Technol
Aubel, D;Fussenegger, M;Sedlmayer, F
Sedlmayer, F: Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
null
321381
165
null
Switzerland
Swiss Fed Inst Technol;Univ Basel;Univ Claude Bernard Lyon 1
Sedlmayer, Ferdinand
null
AUTOMATED DESIGN;BIOLOGY;CONTROLLED TRANSGENE EXPRESSION;DELIVERY;DESIGNER CELLS;ENGINEERED BACTERIA;MAMMALIAN-CELLS;RNA;T-CELLS;TRANSCRIPTIONAL ACTIVATION
Sedlmayer, Ferdinand; Aubel, Dominique; Fussenegger, Martin;
null
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland;Univ Basel, Fac Sci, Basel, Switzerland;Univ Claude Bernard Lyon 1, IUTA Dept Genie Biol, Lyon, France
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland;Univ Basel, Fac Sci, Basel, Switzerland;Univ Claude Bernard Lyon 1, IUTA Dept Genie Biol, Lyon, France
null
null
6
1992;2003;2007;2009;2010;2011;2012;2013;2014;2015;2016;2017;2018
71
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland;Univ Basel, Fac Sci, Basel, Switzerland
Nat. Biomed. Eng
Fussenegger, Martin
NATURE PUBLISHING GROUP
,;actions;also;and;animal;applications;are;areas;autoimmune;autonomously;bacterial;basis;being;biologists;biomarkers;biomedical;blocks;building;by;can;cancer;cells;changing;circuits;clinic;conditions;constantly;construct;controlled;coordinate;cope;corrective;cues;customized;de;describe;designer;designing;developed;devices;diagnostics;discuss;disease;diseases;dosage;employ;enable;engineered;environmental;evolved;experimental;explored;first;for;from;furthermore;gene;genetic;genetically;have;how;human;in;infectious;inspired;laboratory;leap;led;living;made;major;metabolic;models;molecular;monitor;natural;naturally;network's;networks;novo;occurring;of;on;operating;or;organisms;other;owing;particular;pathological;pathways;principles;process;processes;production;proteins;re-adjust;remission;repurposing;review;sensors;signalling;specificity;states;such;survey;synthetic;synthetic-biology;tailored;that;the;therapeutics;this;timing;to;trigger;unbalanced;unprecedented;user-defined;we;with
Swiss Fed Inst Technol;Univ Basel
In living organisms, naturally evolved sensors that constantly monitor and process environmental cues trigger corrective actions that enable the organisms to cope with changing conditions. Such natural processes have inspired biologists to construct synthetic living sensors and signalling pathways, by repurposing naturally occurring proteins and by designing molecular building blocks de novo, for customized diagnostics and therapeutics. In particular, designer cells that employ user-defined synthetic gene circuits to survey disease biomarkers and to autonomously re-adjust unbalanced pathological states can coordinate the production of therapeutics, with controlled timing and dosage. Furthermore, tailored genetic networks operating in bacterial or human cells have led to cancer remission in experimental animal models, owing to the network's unprecedented specificity. Other applications of designer cells in infectious, metabolic and autoimmune diseases are also being explored. In this Review, we describe the biomedical applications of synthetic gene circuits in major disease areas, and discuss how the first genetically engineered devices developed on the basis of synthetic-biology principles made the leap from the laboratory to the clinic.
null
AUTOMATED DESIGN;BIOLOGY;CONTROLLING TRANSGENE EXPRESSION;DELIVERY;DESIGNER CELLS;ENGINEERED BACTERIA;MAMMALIAN-CELLS;RNA;T-CELLS;TRANSCRIPTIONAL ACTIVATION
4
null
null
17
AUTOMATED DESIGN;BIOLOGY;CONTROLLING TRANSGENE EXPRESSION;DELIVERY;DESIGNER CELLS;ENGINEERED BACTERIA;MAMMALIAN-CELLS;RNA;T-CELLS;TRANSCRIPTIONAL ACTIVATION
WOS:000435474500010
Swiss Fed Inst Technol, Basel, Switzerland;Univ Basel, Basel, Switzerland;Univ Claude Bernard Lyon, Lyon, France
France;Switzerland
2,018
null
0000-0001-9877-5549
null
null
English
null
ACS SYNTH BIOL;ADV DRUG DELIVER REV;ALZHEIMERS RES THER;ANGEW CHEM INT EDIT;BIOESSAYS;BIOINFORMATICS;BIOSENS BIOELECTRON;BIOTECHNOL BIOENG;BIOTECHNOL PROGR;BMC MICROBIOL;CANCER-AM CANCER SOC;CELL;CELL CHEM BIOL;CELL REP;CELL STEM CELL;CELL SYST;CSH PERSPECT BIOL;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;CURR OPIN MICROBIOL;DIABETES;EBIOMEDICINE;EXPERT REV VACCINES;FEBS LETT;FRONT IMMUNOL;FRONT MICROBIOL;HUM GENE THER;INTEGR BIOL-UK;J AM CHEM SOC;J BIOL CHEM;J BIOTECHNOL;J CELL BIOL;J CLIN INVEST;J CONTROL RELEASE;J HEPATOL;J MOL BIOL;J VIROL;LAB CHIP;METAB ENG;METHODS MOL BIOL;MICROB CELL FACT;MOL CELL;MOL SYST BIOL;MOL THER;MOL THER-NUCL ACIDS;NANO LETT;NAT BIOMED ENG;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT GENET;NAT MED;NAT METHODS;NAT NANOTECHNOL;NAT PROTOC;NAT REV CLIN ONCOL;NAT REV GENET;NAT REV MICROBIOL;NATURE;NEW ENGL J MED;NUCLEIC ACIDS RES;OBES REV;P NATL ACAD SCI USA;PLOS ONE;SCI TRANSL MED;SCIENCE;TRANSPLANTATION;TRENDS BIOTECHNOL;TRENDS GENET;WIRES SYST BIOL MED
Aubel, Dominique;Fussenegger, Martin;Sedlmayer, Ferdinand
2024-03-11 ER
[Anonymous];Agustín-Pavón, C;Amir, Y;Ando, H;Andries, O;Ausländer, D;Ausländer, S;Bacchus, W;Baeumler, T A;Bai, P;Baig, H;Balazs, A B;Bikard, D;Borrero, J;Bradley, R W;Brazzoli, M;Brophy, J A N;Buffie, C G;Busskamp, V;Caliando, B J;Cameron, D E;Ceroni, F;Chan, C T Y;Chassin, H;Chen, Z Y;Cheng, J K;Citorik, R J;Courbet, A;Daniel, R;Danino, T;Dastor, M;De La Fuente-Nunez, C;Della Peruta, M;Di Bernardo, D;Din, M O;Dormitzer, P R;Duan, F F;Duan, F P;Duportet, X;Ehrhardt, K;Eyjolfsdottir, H;Fischbach, M A;Folcher, M;Gallagher, R R;Geering, B;Gootenberg, J S;Gossen, M;Green, A A;Gröger, A;Gupta, S;Guye, P;Guzmán-Herrador, D L;Haellman, V;Heng, B C;Hirsch, M L;Holowko, M B;Hwang, I Y;Hörner, M;Issa, F;Ittig, S J;Jayaraman, P;Jinek, M;Kawasaki, S;Kemmer, C;Kim, T;Klingemann, H;Kloss, C C;Kojima, R;Konermann, S;Kong, D S;Kong, W;Kotula, J W;Krishnamurthy, M;Krom, R J;Limaye, S A;Liu, Y C;Lu, T K;Luo, X L;Maddalena, A;Manzoni, R;Matsuoka, Y;Maude, S L;Maxmen, A;Miki, K;Mimee, M;Mohammadi, P;Morel, M;Morsut, L;Mátés, L;Müller, K;Müller, M;Nielsen, A A;Nielsen, A A K;Nissim, L;O'Neill, S;Otero-Muras, I;Pardee, K;Park, J S;Perli, S D;Piñero-Lambea, C;Porter, D L;Prasad, V;Prochazka, L;Qudrat, A;Quintero, D;Rajendra, Y;Rezania, A;Riglar, D T;Ronda, C;Roybal, K T;Rubens, J R;Ryu, M H;Rössger, K;Saxena, P;Schukur, L;Schwarz, K A;Sedlmayer, F;Shao, J W;Sheth, R U;Slomovic, S;Smole, A;Steidler, L;Thaiss, C A;Thompson, J A;Wang, H;Weber, W;Weinberg, B H;Wroblewska, L;Wu, H C;Xie, M;Xie, M Q;Xie, Z;Ye, H F;Yin, C R;Yosef, I;You, M X;Zargar, A;Zheng, J H
GJ6DR
Basel, Switzerland;Basel, Switzerland.
79
null
3
null
31,011,195
Aubel, Dominique;Fussenegger, Martin;Sedlmayer, Ferdinand
NAT BIOMED ENG
Basel, Switzerland;Lyon, France
Kremling, A;Löwe, H;Pflüger-Grau, K;Wagner, S G;Ziegler, M
10.1371/journal.pone.0197420
e0197420
1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
28245l642x631d336c723i4d291c1cg3748649
pTRA - A reporter system for monitoring the intracellular dynamics of gene expression
Tech Univ Munich
null
Pflüger-Grau, K (corresponding author), Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany.
null
Kremling, Andreas;Loewe, Hannes;Pflueger-Grau, Katharina;Wagner, Sabine G;Ziegler, Martin
Multidisciplinary Sciences
German Federal Ministry of Education and Research (BMBF) with the Grant SysBioTerp [031A305A]
WOS
Pflüger-Grau, K
Tech Univ Munich, Garching, Germany;Univ Stuttgart, Stuttgart, Germany
13
-;a;dynamics;expression;for;gene;intracellular;monitoring;of;pTRA;Reporter;system;the
1
Lowe, Hannes;Ziegler, Martin
PUBLIC LIBRARY SCIENCE
Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany;Univ Stuttgart, Inst Biochem Engn, Stuttgart, Germany
Article
Tech Univ Munich
SAN FRANCISCO
null
null
Tech Univ Munich;Univ Stuttgart
German Federal Ministry of Education and Research (BMBF) with the Grant SysBioTerp
Pflüger-Grau, K (corresponding author), Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany.
null
Kremling, Andreas;Loewe, Hannes;Pflueger-Grau, Katharina;Wagner, Sabine G;Ziegler, Martin
5
2
432,348,900,057
German Federal Ministry of Education and Research (BMBF) with the Grant SysBioTerp [031A305A]
Germany
PLOS ONE
Germany
null
null
Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany
1932-6203
Kremling, A;Löwe, H;Pflüger-Grau, K;Wagner, S G;Ziegler, M
MAY 17
k.pflueger-grau@tum.de
gene expression;intracellular dynamics;pTRA;reporter system
5
J
Science & Technology - Other Topics
assignment;behaviour;biological parts;BIOLOGY;case study;different genetic setups;end;ESCHERICHIA-COLI;EUROPEAN VECTOR ARCHITECTURE;fluorescent mCherry protein;FLUORESCENT PROTEIN;functions;GENE;gene expression;gene(s);GOI;identified;INFORMATION;interest (GOI);intracellular dynamics;methods;mRNA;optimal combination;plasmid pTRA;potential;prerequisite;protein formation;pTRA;pTRA plasmid;reporter system;SEVA;shortcomings;specific synthetic part;specific transcriptional;standardised tools;successful metabolic engineering;synthetic function;synthetic gene networks;synthetic genetic circuits;toolkit;transcriptional;transcriptional circuits;transcriptional strength;translational activity;translational outputs;understanding;vivo
Wagner, S G
BIOLOGY;ESCHERICHIA-COLI;EUROPEAN VECTOR ARCHITECTURE;FLUORESCENT PROTEIN;SEVA
null
[Wagner, Sabine G.; Ziegler, Martin; Loewe, Hannes; Kremling, Andreas; Pflueger-Grau, Katharina] Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany. [Ziegler, Martin] Univ Stuttgart, Inst Biochem Engn, Stuttgart, Germany.
This work was supported by the German Federal Ministry of Education and Research (BMBF) with the Grant SysBioTerp (Support Code 031A305A) to AK.
assignment;behaviour;biological parts;case study;different genetic setups;end;fluorescent mCherry protein;functions;gene;gene(s);GOI;identified;information;interest (GOI);intracellular dynamics;methods;mRNA;optimal combination;plasmid pTRA;potential;prerequisite;protein formation;pTRA plasmid;shortcomings;specific synthetic part;specific transcriptional;standardised tools;successful metabolic engineering;synthetic function;synthetic gene networks;synthetic genetic circuits;toolkit;transcriptional;transcriptional circuits;transcriptional strength;translational activity;translational outputs;understanding;vivo
10.1007/s00253-002-1158-6;10.1007/s10529-007-9384-8;10.1016/0168-1656(91)90032-Q;10.1016/j.chembiol.2015.04.018;10.1016/j.mib.2016.07.009;10.1016/j.nbt.2017.05.001;10.1021/ja508478x;10.1038/227680a0;10.1038/nature04342;10.1038/NMETH1062;10.1093/nar/gks1119;10.1093/nar/gku1114;10.1101/019927];10.1111/1751-7915.12701
Tech Univ Munich
Kremling, A;Löwe, H;Pflüger-Grau, K;Wagner, S G;Ziegler, M
Wagner, S G: Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany
null
031A305A
15
null
Germany
Tech Univ Munich;Univ Stuttgart
Wagner, Sabine G
Green Published, gold, Green Submitted
BIOLOGY;ESCHERICHIA-COLI;EUROPEAN VECTOR ARCHITECTURE;FLUORESCENT PROTEIN;SEVA
Wagner, Sabine G.; Ziegler, Martin; Loewe, Hannes; Kremling, Andreas; Pflueger-Grau, Katharina;
null
Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany;Univ Stuttgart, Inst Biochem Engn, Stuttgart, Germany
Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany;Univ Stuttgart, Inst Biochem Engn, Stuttgart, Germany
null
null
5
1970;1991;2001;2003;2005;2007;2013;2014;2015;2016;2017;2018
2
Tech Univ Munich, Fac Mech Engn, Syst Biotechnol, Garching, Germany
PLoS One
Pflueger-Grau, Katharina
PUBLIC LIBRARY SCIENCE
(GOI);,;a;accurately;activity;allows;analyse;and;are;as;assignment;based;be;behaviour;biological;by;can;case;circuits;combination;compare;crucial;design;developed;different;discuss;dynamics;encoding;end;engineering;fine-tuning;fluorescent;for;formation;function;functions;gene;gene(s);genetic;GOI;have;identified;important;in;information;interest;intracellular;is;it;many;mCherry;measure;metabolic;methods;mRNA;networks;of;on;optimal;outputs;part;parts;plasmid;potential;predict;prerequisite;presence;protein;pTRA;represent;setups;shortcomings;show;specific;standardised;strength;study;successful;synthetic;systematically;tested;the;this;thus;to;toolkit;tools;transcriptional;translational;understand;understanding;using;vivo;we
Tech Univ Munich
The presence of standardised tools and methods to measure and represent accurately biological parts and functions is a prerequisite for successful metabolic engineering and crucial to understand and predict the behaviour of synthetic genetic circuits. Many synthetic gene networks are based on transcriptional circuits, thus information on transcriptional and translational activity is important for understanding and fine-tuning the synthetic function. To this end, we have developed a toolkit to analyse systematically the transcriptional and translational activity of a specific synthetic part in vivo. It is based on the plasmid pTRA and allows the assignment of specific transcriptional and translational outputs to the gene(s) of interest (GOI) and to compare different genetic setups. By this, the optimal combination of transcriptional strength and translational activity can be identified. The design is tested in a case study using the gene encoding the fluorescent mCherry protein as GOI. We show the intracellular dynamics of mRNA and protein formation and discuss the potential and shortcomings of the pTRA plasmid.
null
BIOLOGY;ESCHERICHIA-COLI;EUROPEAN VECTOR ARCHITECTURE;FLUORESCENT PROTEIN;SEVA
0
null
null
11
ESCHERICHIA-COLI;BIOLOGY;EUROPEAN VECTOR ARCHITECTURE;FLUORESCENT PROTEIN;SEVA
WOS:000432348900057
Tech Univ Munich, Garching, Germany;Univ Stuttgart, Stuttgart, Germany
Germany
2,018
null
0000-0003-2137-5234;0000-0003-3867-6391
null
null
English
null
APPL MICROBIOL BIOT;BioRxiv;BIOTECHNOL LETT;CHEM BIOL;CURR OPIN MICROBIOL;J AM CHEM SOC;J BIOTECHNOL;MICROB BIOTECHNOL;Molecular cloning;NAT METHODS;NATURE;NEW BIOTECHNOL;NUCLEIC ACIDS RES
Kremling, Andreas;Loewe, Hannes;Pflueger-Grau, Katharina;Wagner, Sabine G;Ziegler, Martin
2024-03-11 ER
Borkowski, O;De Lorenzo, V;Endy, D;Filonov, G S;Gawin, A;Gorii-Moreno, A;Hiller, J;Laemmli, U K;Martínez-García, E;Merzlyak, E M;Riesenberg, D;Sambrook J.;Silva-Rocha, R;Terpe, K
GG0DP
Garching, Germany
2
null
2
null
29,772,009
Kremling, Andreas;Loewe, Hannes;Pflueger-Grau, Katharina;Wagner, Sabine G;Ziegler, Martin
PLOS ONE
Garching, Germany;Stuttgart, Germany
Dong, K L;Wang, M Y;Wang, Y D;Ye, H F
10.1002/biot.201700160
1700160
POSTFACH 101161, 69451 WEINHEIM, GERMANY
3p5t4h2w7121y6u3n3z1x3c3z3t1j3m3r5c2l
Engineering Mammalian Designer Cells for the Treatment of Metabolic Diseases
East China Normal Univ
null
Ye, HF (corresponding author), East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China.;Ye, HF (corresponding author), East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China.
SI
Dong, Kaili;Wang, Meiyan;Wang, Yidan;Ye, Haifeng
Biochemical Research Methods;Biotechnology & Applied Microbiology
National Natural Science Foundation of China (NSFC) [31522017]; National Key Research and Development Program of China, Stem Cell, and Translational Research [2016YFA0100300]; NSFC [31470834, 31670869]; Science and Technology Commission of Shanghai Municipality [15QA1401500, 14JC1401700]; Thousand Youth Talents Plan of China
WOS
Ye, H F
East China Normal Univ, Shanghai, Peoples R China
13
Cells;Designer;Diseases;engineering;for;mammalian;Metabolic;of;the;Treatment
1
Wang, Meiyan
WILEY-V C H VERLAG GMBH
East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China;East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China.; Ye, HF (corresponding author), East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China;East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China
Review
East China Normal Univ
WEINHEIM
null
null
East China Normal Univ
National Key Research and Development Program of China, Stem Cell, and Translational Research;National Natural Science Foundation of China (NSFC);NSFC;Science and Technology Commission of Shanghai Municipality;Thousand Youth Talents Plan of China
Ye, HF (corresponding author), East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China.; Ye, HF (corresponding author), East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China.
null
Dong, Kaili;Wang, Meiyan;Wang, Yidan;Ye, Haifeng
35
2
431,621,000,003
National Key Research and Development Program of China, Stem Cell, and Translational Research [2016YFA0100300];National Natural Science Foundation of China (NSFC) [31522017];NSFC [31470834, 31670869];Science and Technology Commission of Shanghai Municipality [15QA1401500, 14JC1401700];Thousand Youth Talents Plan of China
China
BIOTECHNOLOGY JOURNAL
China
null
null
East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China
1860-6768
Dong, K L;Wang, M Y;Wang, Y D;Ye, H F
MAY
hfye@bio.ecnu.edu.cn
engineering Mammalian Designer Cells;Metabolic Diseases;Treatment
4
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
ability;ACTIVATED RECEPTOR-ALPHA;biological systems;clinical applications;closed-loop gene circuits;COREPRESSOR;current technologies;designed cells;DESIGNER CELLS;development;diabetes;engineering Mammalian Designer Cells;engineering principles;future;future perspectives;GENE-EXPRESSION;GLUCOSE-HOMEOSTASIS;HYPERTENSION;hyperuricemia;intelligent manner;mammalian designer cells;MANAGEMENT;Metabolic Diseases;metabolic disorders;METFORMIN;Mice;new functions;new opportunities;number;obesity;open-;recent advances;reprogram cell activities;review;robust therapeutic behaviors;synthetic biology;synthetic designer cells uploaded;synthetic gene;synthetic gene circuits;TRANSGENE EXPRESSION;treatment;URIC-ACID
Wang, Y D
ACTIVATED RECEPTOR-ALPHA;COREPRESSOR;DESIGNER CELLS;GENE-EXPRESSION;GLUCOSE-HOMEOSTASIS;HYPERTENSION;MANAGEMENT;metabolic disorders;METFORMIN;MICE;synthetic gene circuits;TRANSGENE EXPRESSION;URIC-ACID
null
[Wang, Yidan; Wang, Meiyan; Dong, Kaili; Ye, Haifeng] East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China. [Wang, Yidan; Wang, Meiyan; Dong, Kaili; Ye, Haifeng] East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China.
The authors thank Shuyong Liao for the comments on the manuscript. This work was financially supported by the grants from the National Natural Science Foundation of China (NSFC: No. 31522017) for outstanding young scientists, the National Key Research and Development Program of China, Stem Cell, and Translational Research (No. 2016YFA0100300), the NSFC (No. 31470834, No. 31670869), the Science and Technology Commission of Shanghai Municipality (No. 15QA1401500, No. 14JC1401700), and the Thousand Youth Talents Plan of China to H.Y.
ability;biological systems;clinical applications;closed-loop gene circuits;current technologies;designed cells;designer cells;development;diabetes;engineering principles;future;future perspectives;hypertension;hyperuricemia;intelligent manner;mammalian designer cells;metabolic diseases;metabolic disorders;new functions;new opportunities;number;obesity;open-;recent advances;reprogram cell activities;review;robust therapeutic behaviors;synthetic biology;synthetic designer cells uploaded;synthetic gene;treatment
10.1002/anie.201609229;10.1002/bit.21235;10.1007/s12272-016-0871-0;10.1016/j.cell.2013.02.022;10.1016/j.cell.2014.07.022;10.1016/j.copbio.2015.01.010;10.1016/j.ejmech.2012.03.055;10.1016/j.jhep.2016.03.020;10.1016/j.jmb.2005.05.027;10.1016/j.molcel.2014.06.007;10.1016/j.ymben.2013.11.003;10.1016/j.ymben.2015.03.016;10.1016/j.ymthe.2016.11.008;10.1016/S0039-128X(99)00014-8;10.1016/S0140-6736(05)67483-1;10.1016/S0140-6736(14)60460-8;10.1021/acssynbio.6b00257;10.1021/bi034472c;10.1021/sb400182x;10.1037/0003-066X.62.3.220;10.1038/27376;10.1038/83348;10.1038/84448;10.1038/nature03461;10.1038/nature03508;10.1038/nature12271;10.1038/nature21070;10.1038/nbt.1617;10.1038/nbt.1775;10.1038/nbt0912-810b;10.1038/ncomms11247;10.1038/ncomms3825;10.1038/ncomms6392;10.1038/nm.3730;10.1038/nm.3782;10.1038/nprot.2014.038;10.1038/nrendo.2010.19;10.1038/nri912;10.1038/nrmicro2073;10.1038/nrrheum.2012.135;10.1038/nsmb.1983;10.1038/s41551-016-0005;10.1042/BJ20090998;10.1056/NEJMc1102475;10.1056/NEJMoa012512;10.1056/NEJMoa072761;10.1056/NEJMra1110560;10.1073/pnas.040552697;10.1073/pnas.0901501106;10.1073/pnas.0908882107;10.1073/pnas.1216801110;10.1073/pnas.1312414110;10.1073/pnas.88.9.3608;10.1074/jbc.274.22.15901;10.1074/jbc.M405586200;10.1074/jbc.M511095200;10.1081/LRST-200029981;10.1089/hum.1998.9.13-1939;10.1093/nar/gkr1251;10.1093/nar/gkt002;10.1093/nar/gku545;10.1093/nar/gkv1343;10.1093/nar/gkv326;10.1097/00004872-200401000-00003;10.1111/j.1399-5448.2007.00224.x;10.1111/j.1467-789X.2011.00981.x;10.1126/sciadv.1601314;10.1126/science.1203535;10.1126/science.1206843;10.1126/science.1216753;10.1126/science.aaf4006;10.1126/scitranslmed.3005568;10.1126/scitranslmed.aal2298;10.1128/MCB.20.5.1868-1876.2000;10.1155/2014/943162;10.13345/j.cjb.160431;10.15252/msb.20156663;10.2169/internalmedicine.48.1817;10.2174/1389200218666170222150555;10.2174/187221412800604644;10.2337/dc08-1171;10.2337/dc12-1707;10.2337/dc14-2898;10.3109/07388551.2015.1084266;[10.1038/NMETH.1892, 10.1038/nmeth.1892];[10.1038/nphoton.2014.166, 10.1038/NPHOTON.2014.166]
East China Normal Univ
Dong, K L;Wang, M Y;Wang, Y D;Ye, H F
Wang, Y D: East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China
null
14JC1401700;15QA1401500;2016YFA0100300;31470834;31522017;31670869
98
null
China
East China Normal Univ
Wang, Yidan
null
ACTIVATED RECEPTOR-ALPHA;COREPRESSOR;GENE-EXPRESSION;GLUCOSE-HOMEOSTASIS;HYPERTENSION;MANAGEMENT;METFORMIN;MICE;TRANSGENE EXPRESSION;URIC-ACID
Wang, Yidan; Wang, Meiyan; Dong, Kaili; Ye, Haifeng;
null
East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China;East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China
East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China;East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China
1860-7314
designer cells;metabolic disorders;Synthetic gene circuit
5
1989;1991;1992;1998;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
7
East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China;East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China
Biotechnol. J.
Ye, Haifeng
WILEY-V C H VERLAG GMBH
,;a;ability;activities;advanced;advances;an;and;applications;applies;applying;authors;be;behaviors;biological;biology;brought;can;cell;cells;circuits;clinical;closed-loop;constructed;current;design;designed;designer;development;diabetes;discuss;diseases;disorders;engineer;engineering;for;functions;future;gene;has;highlight;hypertension;hyperuricemia;in;including;intelligent;mammalian;manner;metabolic;more;most;new;number;obesity;of;open-;opportunities;or;perform;perspectives;principles;rationally;recent;reprogram;review;revolutionized;robust;significantly;synthetic;systems;technologies;that;the;therapeutic;these;this;to;treat;treating;treatment;uploaded;will;with
East China Normal Univ
Synthetic biology applies engineering principles to biological systems and has significantly advanced the design of synthetic gene circuits that can reprogram cell activities to perform new functions. The ability to engineer mammalian designer cells with robust therapeutic behaviors has brought new opportunities for treating metabolic diseases. In this review, the authors highlight the most recent advances in the development of synthetic designer cells uploaded with open- or closed-loop gene circuits for the treatment of metabolic disorders including diabetes, hypertension, hyperuricemia, and obesity, and discuss the current technologies and future perspectives in applying these designer cells for clinical applications. In the future, more and more rationally designed cells will be constructed and revolutionized to treat a number of metabolic disorders in an intelligent manner.
null
ACTIVATED RECEPTOR-ALPHA;COREPRESSOR;GENE-EXPRESSION;GLUCOSE-HOMEOSTASIS;HYPERTENSION;MANAGEMENT;METFORMIN;MICE;TRANSGENE EXPRESSION;URIC-ACID
2
null
designer cells;metabolic disorders;synthetic gene circuits
11
ACTIVATED RECEPTOR-ALPHA;COREPRESSOR;DESIGNER CELLS;GENE-EXPRESSION;GLUCOSE-HOMEOSTASIS;HYPERTENSION;MANAGEMENT;metabolic disorders;METFORMIN;MICE;synthetic gene circuits;TRANSGENE EXPRESSION;URIC-ACID
WOS:000431621000003
East China Normal Univ, Shanghai, Peoples R China
China
2,018
null
0000-0002-2118-6647
null
null
English
null
ACS SYNTH BIOL;AM PSYCHOL;ANGEW CHEM INT EDIT;ARCH PHARM RES;BEST PRACT RES CLIN;BIOCHEM J;BIOCHEMISTRY-US;BIOSCI TRENDS;BIOTECHNOL BIOENG;BMJ;CARDIOL RES PRACT;CASE BASED GUIDE CLI;CELL;CRIT REV BIOTECHNOL;CURR DRUG METAB;CURR OPIN BIOTECH;DIABETES CARE;EUR J MED CHEM;GLOB HLTH RISKS MORT;HUM GENE THER;INTERNAL MED;J AM COLL CARDIOL;J BIOL CHEM;J HEPATOL;J HYPERTENS;J MOL BIOL;J RECEPT SIG TRANSD;LANCET;METAB ENG;MOL CELL;MOL CELL BIOL;MOL SYST BIOL;MOL THER;NAT BIOMED ENG;NAT BIOTECHNOL;NAT COMMUN;NAT MED;NAT METHODS;NAT PHOTONICS;NAT PROTOC;NAT REV ENDOCRINOL;NAT REV IMMUNOL;NAT REV MICROBIOL;NAT REV RHEUMATOL;NAT STRUCT MOL BIOL;NATURE;NEW ENGL J MED;NUCLEIC ACIDS RES;OBES REV;P NATL ACAD SCI USA;PEDIATR DIABETES;RECENT PATENTS ENDOC;RES PHARM SCI;REV INVEST CLIN;SCI ADV;SCI TRANSL MED;SCIENCE;Sheng Wu Gong Cheng Xue Bao;STEROIDS
Dong, Kaili;Wang, Meiyan;Wang, Yidan;Ye, Haifeng
2024-03-11 ER
2012;[Anonymous];[尹剑丽 Yin Jianli];[邵佳伟 Shao Jiawei];Aguilar, C A;Ausländer, D;Ausländer, S;Bai, P;Basu, S;Beerli, R R;Bellefroid, E J;Bodmer, M;Bothfeld, W;Bouchie, A;Bray G. A.;Chen, X J;Chinetti, G;Daly, M J;Das Kurmi, B;Daynes, R A;Dowell, P;Dumont, J;Fischbach, M A;Folcher, M;Friedman, J M;Fung, E;Gitzinger, M;Gray, L J;Gupta, A;Haas, L;Halford, J C G;Ham, J;Haslam, D W;Heng, B C;Hirsch, I B;Hong, G S;Hsiao, V;Hu, L Y A;Kaur, J;Kearney, P M;Kemmer, C;Khan, A;Kim, T;Knowler, W C;Kumar, R;Lee, H;Legoux, R;Leibiger, I B;Lundberg, C;Mann, T;Messerli, F H;Müller, K;Neve, K A;Ng, M;Nissen, S E;Oberoi, J;Ohno, I;Polonsky, K S;Qi, L S;Roth Ga.;Ruder, W C;Ryu, M H;Rössger, K;Saxena, P;Shao, J W;Singh, M N;Stanley, S A;Stanley, T B;Suh, W;Takebe, T;Terán, W;Therrien, J P;Tschowri, N;Vega, R B;Wang Meiyan;Wang, H;Wang, X;Werner, N S;Wilkinson, S P;Wolfsdorf, J;Xie, M;Xie, M Q;Xue, S;Yamaguchi, T;Yanagisawa R. T.;Yang Linfeng;Yao, F;Ye, H F;Zhang, F;Zhuo, Q
GF0LC
Shanghai, Peoples R China;Shanghai, Peoples R China.
10
null
1
null
29,144,600
Dong, Kaili;Wang, Meiyan;Wang, Yidan;Ye, Haifeng
BIOTECHNOL J
Shanghai, Peoples R China
Barahona, M;Polizzi, K M;Stan, G B;Tomazou, M
10.1016/j.cels.2018.03.013
null
50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
5v4745123a5hj3n4h1y82d442q6k3m5f2p2e6i
Computational Re-design of Synthetic Genetic Oscillators for Independent Amplitude and Frequency Modulation
Imperial Coll London
null
Stan, GB (corresponding author), Imperial Coll London, Dept Bioengn, London SW7 2AZ, England.;Stan, GB (corresponding author), Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England.
null
Barahona, Mauricio;Polizzi, Karen M;Stan, Guy-Bart;Tomazou, Marios
Biochemistry & Molecular Biology;Cell Biology
EPSRC [EP/N014529/1, EP/P009352/1]; UK EPSRC [EP/M002187/1, EP/I032223/1]; EPSRC [EP/I032223/1, EP/N014529/1, EP/P009352/1, EP/M002187/1] Funding Source: UKRI
WOS
Stan, G B
Imperial Coll London, London, England
6
Amplitude;and;computational;for;Frequency;genetic;Independent;modulation;of;Oscillators;Re-design;synthetic
1
Barahona, Mauricio;Polizzi, Karen;Stan, Guy-Bart;Tomazou, Marios
CELL PRESS
Imperial Coll London, Dept Bioengn, London SW7 2AZ, England;Imperial Coll London, Dept Bioengn, London SW7 2AZ, England.; Stan, GB (corresponding author), Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England;Imperial Coll London, Dept Life Sci, London SW7 2AZ, England;Imperial Coll London, Dept Math, London SW7 2AZ, England;Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England
Article
Imperial Coll London
CAMBRIDGE
null
null
Imperial Coll London
EPSRC;UK EPSRC
Stan, GB (corresponding author), Imperial Coll London, Dept Bioengn, London SW7 2AZ, England.; Stan, GB (corresponding author), Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England.
+
Barahona, Mauricio;Polizzi, Karen M;Stan, Guy-Bart;Tomazou, Marios
9
4
432,192,100,013
EPSRC [EP/I032223/1, EP/N014529/1, EP/P009352/1, EP/M002187/1] Funding Source: UKRI;EPSRC [EP/N014529/1, EP/P009352/1];UK EPSRC [EP/M002187/1, EP/I032223/1]
UK
CELL SYSTEMS
UK
null
null
Imperial Coll London, Dept Bioengn, London SW7 2AZ, England
2405-4712
Barahona, M;Polizzi, K M;Stan, G B;Tomazou, M
APR 25
g.stan@imperial.ac.uk
computational Re-design;Frequency Modulation;Independent Amplitude;Synthetic Genetic Oscillators
4
J
Biochemistry & Molecular Biology;Cell Biology
activation;amplitude;amplitude modulation;amplitudes;approach decouples frequency;behavior;biotechnology applications;broad dynamic range;broad range;broader function;building synthetic genetic oscillators;computational Re-design;control;controllable;DEGRADATION;dials;dual-feedback oscillator;DYNAMICS;enzymatic degradation;ESCHERICHIA-COLI;expression;fast oscillation cycles;Frequency Modulation;general design principles;Independent Amplitude;independent control;independent modulation;input;key molecular species;light;need;oscillator's transcription factors;output;period;periods;physiologically reasonable parameters;re-designed;re-designed oscillators;repressilator;REPRESSOR;ROBUST;sink module;Synthetic Genetic Oscillators;translational coupling;tunability-;two classic genetic oscillators;unmet
Tomazou, M
ACTIVATION;DEGRADATION;DYNAMICS;ESCHERICHIA-COLI;EXPRESSION;LIGHT;REPRESSOR;ROBUST
508
[Tomazou, Marios; Stan, Guy-Bart] Imperial Coll London, Dept Bioengn, London SW7 2AZ, England. [Barahona, Mauricio] Imperial Coll London, Dept Math, London SW7 2AZ, England. [Polizzi, Karen M.] Imperial Coll London, Dept Life Sci, London SW7 2AZ, England. [Tomazou, Marios; Barahona, Mauricio; Polizzi, Karen M.; Stan, Guy-Bart] Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England.
M.B. acknowledges funding from EPSRC grant EP/N014529/1 supporting the EPSRC Center for Mathematics of Precision Healthcare. G.B.S. gratefully acknowledges the support of the UK EPSRC through his EPSRC Fellowship for Growth EP/M002187/1, as well as the EPSRC project EP/P009352/1. M.T., M.B., K.P., and G.B.S. gratefully acknowledge the support of the UK EPSRC through project EP/I032223/1.
amplitude;amplitude modulation;amplitudes;approach decouples frequency;behavior;biotechnology applications;broad dynamic range;broad range;broader function;building synthetic genetic oscillators;control;controllable;dials;dual-feedback oscillator;enzymatic degradation;fast oscillation cycles;general design principles;independent control;independent modulation;input;key molecular species;need;oscillator's transcription factors;output;period;periods;physiologically reasonable parameters;re-designed;re-designed oscillators;repressilator;sink module;synthetic genetic oscillators;translational coupling;tunability-;two classic genetic oscillators;unmet
10.1006/jmbi.1994.1434;10.1006/jmbi.1996.0230;10.1007/s001140050704;10.1016/B978-0-12-417029-2.00005-4;10.1016/j.bbamem.2007.07.015;10.1016/j.jmb.2008.10.081;10.1016/j.jmb.2010.10.038;10.1016/j.jmb.2013.07.036;10.1016/j.mib.2016.07.009;10.1016/j.tibtech.2011.09.001;10.1016/S0092-8674(03)00346-5;10.1016/S0955-0674(03)00017-6;10.1021/acssynbio.5b00147;10.1021/sb300060e;10.1021/sb3000639;10.1021/sb500262f;10.1021/sb500273n;10.1023/A:1020611919599;10.1038/35002125;10.1038/481033a;10.1038/msb.2011.94;10.1038/msb4100204;10.1038/nature03508;10.1038/nature04405;10.1038/nature07389;10.1038/nature07616;10.1038/nature08753;10.1038/nature13238;10.1038/nature19841;10.1038/nbt.1591;10.1038/nbt.3053;10.1038/nmeth.2884;10.1063/1.3574387;10.1063/1.4756221;10.1073/pnas.1005615107;10.1073/pnas.1111221108;10.1093/nar/25.6.1203;10.1093/nar/gkp889;10.1093/nar/gkq121;10.1098/rsif.2009.0487;10.1098/rsif.2010.0183;10.1099/mic.0.067975-0;10.1101/014787];10.1103/PhysRevLett.88.148101;10.1109/CDC.2016.7798359;10.1111/dgd.12262;10.1111/j.1365-2958.2005.04798.x;10.1111/j.1749-6632.1991.tb27261.x;10.1126/science.1156951;10.1126/science.2476847;10.1126/science.aac7341;10.1186/1752-0509-1-57;10.1186/1752-0509-8-63;10.1186/1752-0509-8-S4-S4;10.1371/journal.pcbi.1003658;10.1371/journal.pone.0004882;10.1371/journal.pone.0016140;10.3791/50762;10.7554/eLife.09771;10.7554/eLife.23702;[10.1038/NMETH.3339, 10.1038/nmeth.3339]
Imperial Coll London
Barahona, M;Polizzi, K M;Stan, G B;Tomazou, M
Tomazou, M: Imperial Coll London, Dept Bioengn, London SW7 2AZ, England
Barahona, Mauricio
EP/I032223/1;EP/M002187/1;EP/N014529/1;EP/P009352/1
66
null
UK
Imperial Coll London
Tomazou, Marios
Green Submitted, hybrid, Green Published
ACTIVATION;DEGRADATION;DYNAMICS;ESCHERICHIA-COLI;EXPRESSION;LIGHT;REPRESSOR;ROBUST
Tomazou, Marios; Barahona, Mauricio; Polizzi, Karen M.; Stan, Guy-Bart;
null
Imperial Coll London, Dept Bioengn, London SW7 2AZ, England;Imperial Coll London, Dept Life Sci, London SW7 2AZ, England;Imperial Coll London, Dept Math, London SW7 2AZ, England;Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England
Imperial Coll London, Dept Bioengn, London SW7 2AZ, England;Imperial Coll London, Dept Life Sci, London SW7 2AZ, England;Imperial Coll London, Dept Math, London SW7 2AZ, England;Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England
2405-4720
null
4
1963;1989;1991;1994;1996;1997;1999;2000;2002;2003;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
22
Imperial Coll London, Dept Bioengn, London SW7 2AZ, England;Imperial Coll London, Imperial Coll Ctr Synthet Biol, London SW7 2AZ, England
Cell Syst.
Stan, Guy-Bart
CELL PRESS
";,;a;accessible;alleviating;allow;amplitude;amplitudes;an;and;applications;approach;are;be;behavior;between;biotechnology;broad;broader;building;by;can;channeled;characterize;classic;computationally;control;controllable;coupling;currently;cycles;decouples;degradation;demonstrate;design;dials;dual-feedback;dynamic;engineered;enzymatic;explain;facilitates;factors;fast;for;frequency;function;general;genetic;here;how;improve;in;incorporating;independent;input;is;key;maintains;modulation;module;molecular;more;must;need;of;Orthogonal;oscillation;oscillator;oscillator's;oscillators;our;output;over;parameters;perform;period;periods;physiologically;precisely;principles;provide;range;re-designed;reasonable;repressilator;sink;species;synthetic;that;the;this;through;to;transcription;translational;tunability-;two;unmet;we;well;where;while;why
Imperial Coll London
To perform well in biotechnology applications, synthetic genetic oscillators must be engineered to allow independent modulation of amplitude and period. This need is currently unmet. Here, we demonstrate computationally how two classic genetic oscillators, the dual-feedback oscillator and the repressilator, can be re-designed to provide independent control of amplitude and period and improve tunability- that is, a broad dynamic range of periods and amplitudes accessible through the input "dials." Our approach decouples frequency and amplitude modulation by incorporating an orthogonal "sink module" where the key molecular species are channeled for enzymatic degradation. This sink module maintains fast oscillation cycles while alleviating the translational coupling between the oscillator's transcription factors and output. We characterize the behavior of our re-designed oscillators over a broad range of physiologically reasonable parameters, explain why this facilitates broader function and control, and provide general design principles for building synthetic genetic oscillators that are more precisely controllable.
C-3638-2008;M-9747-2019
ACTIVATION;DEGRADATION;DYNAMICS;ESCHERICHIA-COLI;EXPRESSION;LIGHT;REPRESSOR;ROBUST
0
null
null
18
ESCHERICHIA-COLI;ACTIVATION;DEGRADATION;DYNAMICS;EXPRESSION;LIGHT;REPRESSOR;ROBUST
WOS:000432192100013
Imperial Coll London, London, England
UK
2,018
null
0000-0001-5435-2667;0000-0002-0836-5579;0000-0002-1089-5675;0000-0002-5560-902X
null
null
English
null
ACS SYNTH BIOL;AIP CONF PROC;ANN NY ACAD SCI;BBA-BIOMEMBRANES;BioRxiv;BMC SYST BIOL;CELL;CHAOS;CURR OPIN CELL BIOL;CURR OPIN MICROBIOL;DEV GROWTH DIFFER;ELIFE;IEEE DECIS CONTR P;Indian Journal of Pharmaceutical Sciences;International Research Journal of Pharmacy;J MOL BIOL;J PROTEIN CHEM;J R SOC INTERFACE;JOVE-J VIS EXP;LIGHT BASED DYNAMIC;METHOD BIOCHEM ANAL;METHOD MICROBIOL;MICROBIOL-SGM;MOL MICROBIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT METHODS;NATURE;NATURWISSENSCHAFTEN;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV LETT;PLOS COMPUT BIOL;PLOS ONE;SCIENCE;TRENDS BIOTECHNOL
Barahona, Mauricio;Polizzi, Karen M;Stan, Guy-Bart;Tomazou, Marios
2024-03-11 ER
Arora Shweta;Arpino, J A J;Atkinson, M R;Bakken, E E;Borkowski, O;Bozek, K;Cameron, D E;Ceroni, F;Chalfie, M;Chuang, C H;Cookson, N A;Danino, T;Davidson, E A;Del Vecchio, D;Didovyk, A;Elowitz, M B;Farrell, C M;Fung, E;Galkin, V E;Gjuvsland, A B;Goers, L;Goodwin B.;Hasty, J;Hess, B;Kedracka-Krok, S;Levskaya, A;Lewis, D;Lu, T K;Lutz, R;Lux, M W;Milo, R;Moriya, T;Natale, P;Niederholtmeyer, H;Nielsen, A A K;Olson, E J;Potvin-Trottier, L;Prindle, A;Purcell, O;Qian, Y L;Ritika S.;Schmid, S R;Shis, D L;Sowa, S W;Steipe, B;Strelkowa, N;Stricker, J;Sun, Z Z;Tabor, J J;Tigges, M;Toettcher, J E;Tomazou M.;Tsai, T Y C;Tyson, J J;Uriu, K;Utsumi, R;Voigt, C A;Weisse A. Y.;Wu, F Q;Zhang, X
GF8BF
London, England;London, England.
24
null
1
null
29,680,377
Barahona, Mauricio;Polizzi, Karen M;Stan, Guy-Bart;Tomazou, Marios
CELL SYST
London, England
Song, A G;Zhang, L;Zheng, W B
10.1063/1.5019297
043117
1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
2i2z1l67236zu3w3pm3z4268502g1j4f4i1n51
Adaptive logical stochastic resonance in time-delayed synthetic genetic networks
Nanjing Normal Univ
null
Zhang, L (corresponding author), Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China.
null
Song, Aiguo;Zhang, Lei;Zheng, Wenbin
Mathematics, Applied;Physics, Mathematical
National Science Foundation of China [61203237]; Industry-Academia Cooperation Innovation Fund Projection of Jiangsu Province [BY2016001-02]
WOS
Zhang, L
Chengdu Univ Informat Technol, Sichuan, Peoples R China;Nanjing Normal Univ, Jiangsu, Peoples R China;Southeast Univ, Jiangsu, Peoples R China
28
adaptive;genetic;in;logical;networks;resonance;stochastic;synthetic;time-delayed
1
Song, Aiguo;Zhang, Lei
AMER INST PHYSICS
Chengdu Univ Informat Technol, Coll Software Engn, Chengdu 610225, Sichuan, Peoples R China;Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China;Southeast Univ, Sch Instrument Sci & Engn, Sipailou 2, Nanjing 210096, Jiangsu, Peoples R China
Article
Nanjing Normal Univ
MELVILLE
null
null
Chengdu Univ Informat Technol;Nanjing Normal Univ;Southeast Univ
Industry-Academia Cooperation Innovation Fund Projection of Jiangsu Province;National Science Foundation of China
Zhang, L (corresponding author), Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China.
null
Song, Aiguo;Zhang, Lei;Zheng, Wenbin
42
3
431,142,000,021
Industry-Academia Cooperation Innovation Fund Projection of Jiangsu Province [BY2016001-02];National Science Foundation of China [61203237]
China
CHAOS
China
null
null
Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China
1054-1500
Song, A G;Zhang, L;Zheng, W B
APR
leizhang@njnu.edu.cn
adaptive logical stochastic resonance;time-delayed synthetic genetic networks
3
J
Mathematics;Physics
adaptive logical stochastic resonance;AIP Publishing;background noise;bacteriophage lambda;clear logic operation;concept;contrast;designing new genetic regulatory networks paradigm;desired logic response;hand;larger range;latch operation;length;logic operation;LOGICAL STOCHASTIC RESONANCE;modulated periodic force;NETWORK;noise;one hand;optimal noise plateau;possible help;previous synthetic genetic networks;proposed system;result;stability;SYSTEM;time-delay;time-delayed synthetic genetic networks;tuning time-delay;two advantages;varying noise intensity
Zhang, L
NOISE;STABILITY
null
[Zhang, Lei] Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China. [Zheng, Wenbin] Chengdu Univ Informat Technol, Coll Software Engn, Chengdu 610225, Sichuan, Peoples R China. [Song, Aiguo] Southeast Univ, Sch Instrument Sci & Engn, Sipailou 2, Nanjing 210096, Jiangsu, Peoples R China.
The work was supported by the National Science Foundation of China (No. 61203237) and the Industry-Academia Cooperation Innovation Fund Projection of Jiangsu Province (BY2016001-02).
AIP Publishing;background noise;bacteriophage lambda;clear logic operation;concept;contrast;designing new genetic regulatory networks paradigm;desired logic response;hand;larger range;latch operation;length;logic operation;logical stochastic resonance;modulated periodic force;network;one hand;optimal noise plateau;possible help;previous synthetic genetic networks;proposed system;result;system;time-delay;time-delayed synthetic genetic networks;tuning time-delay;two advantages;varying noise intensity
10.1007/s11071-013-1136-9;10.1016/j.chemphys.2010.06.015;10.1016/j.cnsns.2013.12.008;10.1016/j.physleta.2012.01.039;10.1021/nl9034175;10.1038/35002125;10.1038/nature01257;10.1038/nature07389;10.1038/nbt1413;10.1063/1.1345702;10.1063/1.3245318;10.1063/1.4984806;10.1103/PhysRevE.71.031106;10.1103/PhysRevE.82.051106;10.1103/PhysRevE.84.055201;10.1103/PhysRevLett.102.104101;10.1103/PhysRevLett.82.2811;10.1103/PhysRevLett.87.250602;10.1103/PhysRevLett.90.020601;10.1109/TCSI.2006.883882;10.1109/TCSII.2007.901631;10.1109/TNNLS.2015.2495155;10.1209/0295-5075/93/18001;10.1371/journal.pone.0076032
Nanjing Normal Univ
Song, A G;Zhang, L;Zheng, W B
Zhang, L: Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China
Zhang, Lei
61203237;BY2016001-02
25
null
China
Chengdu Univ Informat Technol;Nanjing Normal Univ;Southeast Univ
Zhang, Lei
null
NOISE;STABILITY
Zhang, Lei; Zheng, Wenbin; Song, Aiguo;
null
Chengdu Univ Informat Technol, Coll Software Engn, Chengdu 610225, Sichuan, Peoples R China;Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China;Southeast Univ, Sch Instrument Sci & Engn, Sipailou 2, Nanjing 210096, Jiangsu, Peoples R China
Chengdu Univ Informat Technol, Coll Software Engn, Chengdu 610225, Sichuan, Peoples R China;Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China;Southeast Univ, Sch Instrument Sci & Engn, Sipailou 2, Nanjing 210096, Jiangsu, Peoples R China
1089-7682
null
4
1999;2000;2001;2002;2003;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2016;2017
31
Nanjing Normal Univ, Sch Elect & Automat Engn, Nanjing 210046, Jiangsu, Peoples R China
Chaos
Song, Aiguo
AMER INST PHYSICS
,;a;adapt;adding;advantages;AIP;and;applied;background;bacteriophage;based;be;by;can;clear;concept;contrast;derived;designing;desired;extend;for;force;from;genetic;hand;has;help;implement;in;increase;intensity;is;lambda;larger;latch;length;logic;logical;make;modulated;network;networks;new;noise;obtained;obtaining;of;on;one;operation;optimal;other;paper;paradigm;periodic;plateau;possible;previous;proposed;provides;published;Publishing;range;regulatory;resonance;response;result;stochastic;synthetic;system;the;time-delay;time-delayed;to;tuned;tuning;two;varying;when;with
Nanjing Normal Univ
In the paper, the concept of logical stochastic resonance is applied to implement logic operation and latch operation in time-delayed synthetic genetic networks derived from a bacteriophage lambda. Clear logic operation and latch operation can be obtained when the network is tuned by modulated periodic force and time-delay. In contrast with the previous synthetic genetic networks based on logical stochastic resonance, the proposed system has two advantages. On one hand, adding modulated periodic force to the background noise can increase the length of the optimal noise plateau of obtaining desired logic response and make the system adapt to varying noise intensity. On the other hand, tuning time-delay can extend the optimal noise plateau to larger range. The result provides possible help for designing new genetic regulatory networks paradigm based on logical stochastic resonance. Published by AIP Publishing.
AGI-2713-2022;C-9699-2009
NOISE;STABILITY
2
null
null
7
NOISE;STABILITY
WOS:000431142000021
Chengdu Univ Informat Technol, Sichuan, Peoples R China;Nanjing Normal Univ, Jiangsu, Peoples R China;Southeast Univ, Jiangsu, Peoples R China
China
2,018
null
0000-0001-8749-7459;0000-0002-1982-6780
null
null
English
null
APPL PHYS LETT;CHAOS;CHEM PHYS;COMMUN NONLINEAR SCI;EPL-EUROPHYS LETT;IEEE T CIRCUITS-I;IEEE T CIRCUITS-II;IEEE T NEUR NET LEAR;J Biol Eng;NANO LETT;NAT BIOTECHNOL;NATURE;NONLINEAR DYNAM;PHYS LETT A;PHYS REV E;PHYS REV LETT;PLOS ONE
Song, Aiguo;Zhang, Lei;Zheng, Wenbin
2024-03-11 ER
Bulsara, A R;Canton, B;Dari, A;Elowitz, M B;Frank, T D;Guerra, D N;Gupta, A;Hasty, J;Hellen, E H;Kohar, V;Li, C G;Masoller, C;Murali, K;Nistala G. J.;Ohira, T;Sharma, A;Stricker, J;Tsimring, L S;Wang, N;Wu, J;Zhang, L
GE3VW
Jiangsu, Peoples R China
36
null
3
null
31,906,654
Song, Aiguo;Zhang, Lei;Zheng, Wenbin
CHAOS
Jiangsu, Peoples R China;Sichuan, Peoples R China
Brandao, R M S D;da Silva, A S;de Andrade, H M;do Monte, S J;Faria, A R;Martins, L M S
10.2217/fmb-2017-0184
null
UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND
t4t6i13562w604k166n505v3p4x5z1e6w6y6s12
Novel recombinant multiepitope proteins for the detection of anti-<i>Cryptococcus </i>antibodies
Univ Fed Piaui
null
Brandao, RMSD (corresponding author), Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil.
null
da Silva, Adalberto Socorro;de Andrade, Helida Monteiro;Faria, Angelica Rosa;Hadad do Monte, Semiramis Jamil;Santos de Serpa Brandao, Rafael Melo;Soares Martins, Liline Maria
Microbiology
Laboratorio de Imunogenetica e Biologia Molecular, Universidade Federal do Piaui, Brazil; Laboratorio de Imunogenetica e Biologia Molecular (LIB/UFPI)
WOS
Brandao, RMSD
Univ Estadual Piaui, Piaui, Brazil;Univ Fed Minas Gerais, Belo Horizonte MG, Brazil;Univ Fed Piaui, Piaui, Brazil
13
</i>antibodies;anti-<i>Cryptococcus;detection;for;multiepitope;novel;of;Proteins;recombinant;the
1
Brandao, Rafael
FUTURE MEDICINE LTD
Univ Estadual Piaui, Ctr Ciencias Saude, BR-64001280 Teresina, Piaui, Brazil;Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, BR-31279910 Belo Horizonte, MG, Brazil;Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil
Article
Univ Fed Piaui
LONDON
null
null
Univ Estadual Piaui;Univ Fed Minas Gerais;Univ Fed Piaui
Laboratorio de Imunogenetica e Biologia Molecular (LIB/UFPI);Laboratorio de Imunogenetica e Biologia Molecular, Universidade Federal do Piaui, Brazil
Brandao, RMSD (corresponding author), Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil.
436
da Silva, Adalberto Socorro;de Andrade, Helida Monteiro;Faria, Angelica Rosa;Hadad do Monte, Semiramis Jamil;Santos de Serpa Brandao, Rafael Melo;Soares Martins, Liline Maria
2
3
432,198,800,006
Laboratorio de Imunogenetica e Biologia Molecular (LIB/UFPI);Laboratorio de Imunogenetica e Biologia Molecular, Universidade Federal do Piaui, Brazil
Brazil
FUTURE MICROBIOLOGY
Brazil
null
null
Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil
1746-0913
Brandao, R M S D;da Silva, A S;de Andrade, H M;do Monte, S J;Faria, A R;Martins, L M S
MAR
brandaorafael@hotmail.com
anti-<i>Cryptococcus </i>antibodies;detection;novel recombinant multiepitope proteins
6
J
Microbiology
100%;88.57%;aim;alternative assay;anti-<i>Cryptococcus </i>antibodies;anti-Cryptococcus antibodies;antigens;attempt;B;C;coding sequences;conclusion;cryptococcosis;D. Results;detection;Diagnosis;ELISA;Escherichia coil;four genes;GATTII INFECTION;GLOBAL BURDEN;good results;HIV PATIENTS;materials;MENINGITIS;methods;multiepitope protein;multiepitope proteins;novel recombinant multiepitope proteins;peptides;potential antigens;protein D;proteins;PULMONARY CRYPTOCOCCOSIS;recombinant multiepitope proteins;results;sensitivity;SERODIAGNOSIS;serological diagnosis;silico analyses;specificity;synthetic gene;synthetic genes;synthetic peptides;test recombinant multiepitope proteins;union
Brandao, R M S D
antigens;cryptococcosis;DIAGNOSIS;ELISA;GATTII INFECTION;GLOBAL BURDEN;HIV PATIENTS;MENINGITIS;multiepitope protein;PULMONARY CRYPTOCOCCOSIS;SERODIAGNOSIS;serological diagnosis;Synthetic gene
429
[Santos de Serpa Brandao, Rafael Melo; Soares Martins, Liline Maria; da Silva, Adalberto Socorro; Hadad do Monte, Semiramis Jamil] Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil. [Faria, Angelica Rosa; de Andrade, Helida Monteiro] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, BR-31279910 Belo Horizonte, MG, Brazil. [Soares Martins, Liline Maria] Univ Estadual Piaui, Ctr Ciencias Saude, BR-64001280 Teresina, Piaui, Brazil.
This work was supported by the Laboratorio de Imunogenetica e Biologia Molecular, Universidade Federal do Piaui, Brazil. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.; The American Journal of Experts conducted the review of the English language of the manuscript, funded by the Laboratorio de Imunogenetica e Biologia Molecular (LIB/UFPI).
100%;88.57%;aim;alternative assay;anti-Cryptococcus antibodies;attempt;B;C;coding sequences;conclusion;cryptococcosis;D. Results;diagnosis;Escherichia coil;four genes;good results;materials;methods;multiepitope proteins;peptides;potential antigens;protein D;proteins;recombinant multiepitope proteins;results;sensitivity;serological diagnosis;silico analyses;specificity;synthetic genes;synthetic peptides;test recombinant multiepitope proteins;union
10.1002/jcla.20483;10.1007/s00018-004-4464-6;10.1016/j.bjid.2012.07.004;10.1016/j.bjid.2012.10.020;10.1016/j.fgb.2014.10.003;10.1016/j.idc.2015.10.004;10.1016/S0035-9203(96)90297-7;10.1016/S0167-5877(00)00115-X;10.1038/227680a0;10.1038/nrmicro.2015.6;10.1093/cid/cir379;10.1093/cid/cis529;10.1093/cid/civ041;10.1097/MCP.0b013e32835f1ad1;10.1097/QAD.0b013e328322ffac;10.1111/j.1439-0507.2008.01549.x;10.1128/CDLI.9.4.883-891.2002;10.1128/CVI.00189-08;10.1128/CVI.00383-07;10.1128/CVI.00446-12;10.1128/CVI.05553-11;10.1128/JCM.00751-17;10.1128/microbiolspec.EI10-0016-2016;10.1185/03007995.2012.761134;10.1186/1471-2148-8-19;10.1186/s13071-015-0932-0;10.1371/journal.pntd.0003429;10.1371/journal.pntd.0004885;10.1371/journal.pone.0161100;10.1542/peds.107.5.e66;10.3109/13693786.2011.564216;[10.2217/FMB.13.22, 10.2217/fmb.13.22];[10.2217/fmb.14.49, 10.2217/FMB.14.49]
Univ Fed Piaui
Brandao, R M S D;da Silva, A S;de Andrade, H M;do Monte, S J;Faria, A R;Martins, L M S
Brandao, R M S D: Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil
null
null
37
null
Brazil
Univ Estadual Piaui;Univ Fed Minas Gerais;Univ Fed Piaui
Santos de Serpa Brandao, Rafael Melo
null
DIAGNOSIS;GATTII INFECTION;GLOBAL BURDEN;HIV PATIENTS;MENINGITIS;PULMONARY CRYPTOCOCCOSIS;SERODIAGNOSIS
Santos de Serpa Brandao, Rafael Melo; Faria, Angelica Rosa; de Andrade, Helida Monteiro; Soares Martins, Liline Maria; da Silva, Adalberto Socorro; Hadad do Monte, Semiramis Jamil;
null
Univ Estadual Piaui, Ctr Ciencias Saude, BR-64001280 Teresina, Piaui, Brazil;Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, BR-31279910 Belo Horizonte, MG, Brazil;Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil
Univ Estadual Piaui, Ctr Ciencias Saude, BR-64001280 Teresina, Piaui, Brazil;Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, BR-31279910 Belo Horizonte, MG, Brazil;Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil
1746-0921
Antigenicity;cryptococcosis;ELISA;multiepitope protein;serological diagnosis;Synthetic gene
4
1970;1996;2000;2001;2002;2005;2008;2009;2011;2012;2013;2014;2015;2016;2017
4
Univ Fed Piaui, Lab Imunogenet & Biol Mol, Campus Ministro Petronio Portella Bloco SG 16, BR-64049550 Teresina, Piaui, Brazil
Future Microbiol.
Hadad do Monte, Semiramis Jamil
FUTURE MEDICINE LTD
&;,;100%;88.57%;:;;;a;aim;all;alternative;an;analyses;and;anti-Cryptococcus;antibodies;antigens;as;assay;assembled;attempt;B;be;been;best;C;cloned;coding;coil;conclusion;constructs;cryptococcosis;D;D.;detect;diagnosis;Escherichia;expressed;for;four;genes;good;have;here;however;improve;in;into;materials;methods;multiepitope;of;peptides;potential;previously;produce;producing;protein;proteins;recombinant;results;sensitivity;sequences;serological;showed;shown;silico;specificity;synthetic;test;that;the;these;to;union;used;were;with;would;yielded
Univ Fed Piaui
Aim: To produce and test recombinant multiepitope proteins as an alternative assay for the serological diagnosis of cryptococcosis. Materials & methods: Previously, synthetic peptides were used to detect anti-Cryptococcus antibodies, and in silico analyses showed that the union of peptides would improve the results. Here, the coding sequences of these peptides were assembled into synthetic genes. Four genes have been cloned and expressed in Escherichia coil, producing recombinant multiepitope proteins: proteins A, B, C and D. Results: All constructs yielded good results; however, protein D showed the best results, with a sensitivity of 88.57% and specificity of 100%. Conclusion: The multiepitope proteins were shown to be potential antigens for the diagnosis of cryptococcosis in an attempt to detect anti-Cryptococcus antibodies.
null
DIAGNOSIS;GATTII INFECTION;GLOBAL BURDEN;HIV PATIENTS;MENINGITIS;PULMONARY CRYPTOCOCCOSIS;SERODIAGNOSIS
1
null
antigens;cryptococcosis;ELISA;multiepitope protein;serological diagnosis;Synthetic gene
8
ANTIGEN;cryptococcosis;DIAGNOSIS;ELISA;GATTII INFECTION;GLOBAL BURDEN;HIV PATIENTS;MENINGITIS;multiepitope protein;PULMONARY CRYPTOCOCCOSIS;SERODIAGNOSIS;serological diagnosis;Synthetic gene
WOS:000432198800006
Univ Estadual Piaui, Piaui, Brazil;Univ Fed Minas Gerais, Belo Horizonte MG, Brazil;Univ Fed Piaui, Piaui, Brazil
Brazil
2,018
null
0000-0002-8718-7140
null
null
English
null
AIDS;BMC EVOL BIOL;BRAZ J INFECT DIS;CELL MOL LIFE SCI;CLIN DIAGN LAB IMMUN;CLIN INFECT DIS;CLIN VACCINE IMMUNOL;CURR MED RES OPIN;CURR OPIN PULM MED;FUNGAL GENET BIOL;FUTURE MICROBIOL;HEPAT RES TREAT;INDIAN J MED RES;INFECT DIS CLIN N AM;INT J CLIN EXP MED;J CLIN LAB ANAL;J CLIN MICROBIOL;MED MYCOL;MICROBIOL SPECTR;MYCOSES;NAT REV MICROBIOL;NATURE;PARASITE VECTOR;PEDIATRICS;PLOS NEGLECT TROP D;PLOS ONE;PREV VET MED;T ROY SOC TROP MED H;WHO TECH REP SER
da Silva, Adalberto Socorro;de Andrade, Helida Monteiro;Faria, Angelica Rosa;Hadad do Monte, Semiramis Jamil;Santos de Serpa Brandao, Rafael Melo;Soares Martins, Liline Maria
2024-03-11 ER
Binnicker, M J;Brandao, R M S D;Brocchieri, L;Chai, H C;Chen, S C A;Cheng, Z;Dai, J F;Dubbels, M;Faria, A R;Galdino, A S;Goldman, D L;Greiner, M;Hajissa, K;Hayes, G E;Houghton, R L;Laemmli, U K;Lin, X;Lindsley, M D;Lockhart, S R;Martins, L M S;May, R C;Mayer, M P;Morera, N;Park, B J;Perfect, J R;Phillips, P;Saha, D C;Santos, F L N;Seaton, R A;Souto, A C P;Vallabhaneni, S;Vidal, J E;Who;Xie, X N;Yu, J Q;Zhuang, D
GF8DO
Piaui, Brazil
4
null
3
null
29,125,786
da Silva, Adalberto Socorro;de Andrade, Helida Monteiro;Faria, Angelica Rosa;Hadad do Monte, Semiramis Jamil;Santos de Serpa Brandao, Rafael Melo;Soares Martins, Liline Maria
FUTURE MICROBIOL
Belo Horizonte MG, Brazil;Piaui, Brazil
Bervoets, I;Charlier, D;De Mey, M;Maertens, J;Van Brempt, M;Van Hove, B;Van Nerom, K
10.1093/nar/gky010
null
GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
1s3k1bc40s67j4o4v3e632e3c1h2r693y1w5f
A sigma factor toolbox for orthogonal gene expression in <i>Escherichia coli</i>
Vrije Univ Brussel
null
Charlier, D (corresponding author), Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium.
null
Bervoets, Indra;Charlier, Daniel;De Mey, Marjan;Maertens, Jo;Van Brempt, Maarten;Van Hove, Bob;Van Nerom, Katleen
Biochemistry & Molecular Biology
Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0321.13N]; Ghent University Special Research Fund [BOF16/IOP/040]; Fonds voor Wetenschappelijk onderzoek Vlaanderen (FWO-Vlaanderen); Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)
WOS
Charlier, D
Univ Ghent, Ghent, Belgium;Vrije Univ Brussel, Brussels, Belgium
46
<i>Escherichia;a;coli</i>;expression;factor;for;gene;in;Orthogonal;sigma;Toolbox
1
Bervoets, Indra;Charlier, Daniel;De Mey, Marjan
OXFORD UNIV PRESS
Univ Ghent, Dept Biotechnol, CSB, B-9000 Ghent, Belgium;Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium
Article
Vrije Univ Brussel
OXFORD
null
null
Univ Ghent;Vrije Univ Brussel
Fonds voor Wetenschappelijk Onderzoek Vlaanderen;Fonds voor Wetenschappelijk onderzoek Vlaanderen (FWO-Vlaanderen);Ghent University Special Research Fund;Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)
Charlier, D (corresponding author), Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium.
2144
Bervoets, Indra;Charlier, Daniel;De Mey, Marjan;Maertens, Jo;Van Brempt, Maarten;Van Hove, Bob;Van Nerom, Katleen
51
2
426,293,300,048
Fonds voor Wetenschappelijk onderzoek Vlaanderen (FWO-Vlaanderen);Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0321.13N];Ghent University Special Research Fund [BOF16/IOP/040];Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)
Belgium
NUCLEIC ACIDS RESEARCH
Belgium
null
null
Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium
0305-1048
Bervoets, I;Charlier, D;De Mey, M;Maertens, J;Van Brempt, M;Van Hove, B;Van Nerom, K
FEB 28
dcharlie@vub.ac.be
<i>Escherichia coli</i>;orthogonal gene expression;sigma factor toolbox
7
J
Biochemistry & Molecular Biology
<i>Escherichia coli</i>;analyzed sigma factors;assembly;Bacillus subtilis;BACILLUS-SUBTILIS;CELL-ENVELOPE;circuit;CIRCUITS;complex synthetic genetic systems;conditions;control;DESIGN;different sensory signals;directed evolution;dynamic control;Escherichia coli;EXTRACYTOPLASMIC-FUNCTION SIGMA(X);four;future;gene expression;Genetic circuits;heterologous sigma factors;host;IDENTIFICATION;IN-VIVO;interesting expansion;interference;loss;multigene pathways;multiple outputs;orthogonal expression;orthogonal expression systems;orthogonal gene expression;orthogonal manner;orthogonal nature;orthogonally;PATHWAY;programmable control;promoter libraries;regulation systems;response;result;separate modules;shortage;sigma factor toolbox;size;specific promoter sequences;stay;synthetic biology;synthetic biology toolbox;synthetic genetic sensors;three sigma factors;timing;toolbox;TRANSCRIPTION;transcription initiation frequencies;tuning;undesired crosstalk;use;wide range
Bervoets, I
BACILLUS-SUBTILIS;CELL-ENVELOPE;DESIGN;directed evolution;EXTRACYTOPLASMIC-FUNCTION SIGMA(X);IDENTIFICATION;IN-VIVO;PATHWAY;Synthetic biology;TRANSCRIPTION
2133
[Bervoets, Indra; Van Nerom, Katleen; Charlier, Daniel] Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium. [Van Brempt, Maarten; Van Hove, Bob; Maertens, Jo; De Mey, Marjan] Univ Ghent, Dept Biotechnol, CSB, B-9000 Ghent, Belgium.
Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0321.13N to M.D.M., D.C.]; Ghent University Special Research Fund [BOF16/IOP/040 to M.D.M.]; Fonds voor Wetenschappelijk onderzoek Vlaanderen (FWO-Vlaanderen) (to BVH); Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) Ph.D. Grant (to M.V.B.). Funding for open access charge: Fonds Wetenschappelijk Onderzoek [G.0321.13N].
analyzed sigma factors;assembly;Bacillus subtilis;circuit;circuits;complex synthetic genetic systems;conditions;control;different sensory signals;dynamic control;Escherichia coli;four;future;gene expression;genetic circuits;heterologous sigma factors;host;interesting expansion;interference;loss;multigene pathways;multiple outputs;orthogonal expression;orthogonal expression systems;orthogonal manner;orthogonal nature;orthogonally;programmable control;promoter libraries;regulation systems;response;result;separate modules;shortage;sigma factor toolbox;size;specific promoter sequences;stay;synthetic biology toolbox;synthetic genetic sensors;three sigma factors;timing;toolbox;transcription initiation frequencies;tuning;undesired crosstalk;use;wide range
10.1006/jmbi.2001.5372;10.1007/s10295-016-1862-3;10.1016/0378-1119(79)90082-9;10.1016/j.biotechadv.2015.02.011;10.1016/j.biotechadv.2016.02.012;10.1016/j.cbpa.2016.08.003;10.1016/j.cell.2013.02.022;10.1016/j.cell.2014.10.002;10.1016/j.copbio.2014.11.013;10.1016/j.enzmictec.2014.10.006;10.1016/j.jbiotec.2013.07.030;10.1016/j.jmb.2006.01.059;10.1016/j.jmb.2015.10.004;10.1016/j.mib.2004.10.001;10.1016/j.mib.2008.10.002;10.1016/j.tibtech.2016.02.010;10.1016/j.ymben.2010.10.006;10.1016/j.ymben.2012.08.007;10.1016/j.ymben.2014.02.012;10.1016/S1369-5274(02)00372-7;10.1021/acssynbio.7b00017;10.1021/ja805203w;10.1021/sb500299c;10.1038/msb.2013.58;10.1038/nature10965;10.1038/nature12051;10.1038/nbt.1555;10.1038/nbt.1568;10.1038/nbt.2461;10.1038/nchembio.1411;10.1038/ncomms2425;10.1038/nrg3227;10.1038/nrmicro3240;10.1038/nrmicro750;10.1038/nrmicro787;10.1073/pnas.0600828103;10.1073/pnas.0900267106;10.1073/pnas.120163297;10.1073/pnas.1220157110;10.1073/pnas.89.11.5123;10.1093/nar/28.18.3497;10.1093/nar/gkg694;10.1093/nar/gkq810;10.1093/nar/gkr1288;10.1093/nar/gks597;10.1093/nar/gkt520;10.1093/nar/gku829;10.1111/j.1365-2958.2007.06090.x;10.1126/science.1191652;10.1126/science.1193990;10.1126/science.1214547;10.1128/jb.173.24.7867-7874.1991;10.1128/jb.174.12.3843-3849.1992;10.1128/JB.180.8.2057-2062.1998;10.1128/JB.181.18.5718-5724.1999;10.1128/JB.183.12.3623-3630.2001;10.1128/JB.183.6.1921-1927.2001;10.1128/JB.184.17.4881-4890.2002;10.1128/JB.186.4.1136-1146.2004;10.1128/MMBR.69.4.527-543.2005;10.1146/annurev-chembioeng-061312-103312;10.1146/annurev.micro.57.030502.090913;10.1186/1472-6750-10-26;10.1186/1472-6750-7-34;10.1186/1475-2859-12-56;10.1371/journal.pcbi.1002811;10.1371/journal.pone.0006441;10.1371/journal.pone.0179181;10.15252/msb.20145299;10.3389/fpls.2015.00007;10.3390/biom5031245;[10.1038/NMETH.2404, 10.1038/nmeth.2404];[10.1371/journal.pone.0016765, 10.4161/bbug.3.1.18223]
Vrije Univ Brussel
Bervoets, I;Charlier, D;De Mey, M;Maertens, J;Van Brempt, M;Van Hove, B;Van Nerom, K
Bervoets, I: Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium
De Mey, Marjan
BOF16/IOP/040;G.0321.13N
76
null
Belgium
Univ Ghent;Vrije Univ Brussel
Bervoets, Indra
Green Published, Green Submitted, gold
BACILLUS-SUBTILIS;CELL-ENVELOPE;DESIGN;DIRECTED EVOLUTION;EXTRACYTOPLASMIC-FUNCTION SIGMA(X);IDENTIFICATION;IN-VIVO;PATHWAY;SYNTHETIC BIOLOGY;TRANSCRIPTION
Bervoets, Indra; Van Brempt, Maarten; Van Nerom, Katleen; Van Hove, Bob; Maertens, Jo; De Mey, Marjan; Charlier, Daniel;
null
Univ Ghent, Dept Biotechnol, CSB, B-9000 Ghent, Belgium;Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium
Univ Ghent, Dept Biotechnol, CSB, B-9000 Ghent, Belgium;Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium
1362-4962
null
4
1979;1991;1992;1998;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
57
Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Microbiol, Pl Laan 2, B-1050 Brussels, Belgium
Nucleic Acids Res.
Charlier, Daniel
OXFORD UNIV PRESS
,;a;additionally;allow;an;analyzed;and;are;as;assembly;Bacillus;based;be;between;biology;but;by;can;circuit;circuits;coli;combined;complex;complexity;conditions;constitutes;contribute;control;covers;creating;crosstalk;different;dynamic;each;enable;enables;Escherichia;expanded;expansion;expression;factor;factors;for;four;frequencies;from;function;future;gene;genetic;growing;heterologous;host;in;incorporated;increasingly;initiation;interesting;interference;into;is;it;libraries;limited;loss;manner;may;minimize;modules;more;multigene;multiple;nature;needed;of;on;Orthogonal;orthogonally;other;outputs;over;parts;pathways;presents;programmable;promoter;range;recognize;regulation;regulatory;response;result;sensors;sensory;separate;sequences;set;shortage;sigma;signals;size;specific;stay;subtilis;synthetic;systems;that;the;their;therefore;this;three;timing;to;toolbox;toward;transcription;tuning;undesired;up;use;used;wide;without;work
Vrije Univ Brussel
Synthetic genetic sensors and circuits enable programmable control over timing and conditions of gene expression and, as a result, are increasingly incorporated into the control of complex and multigene pathways. Size and complexity of genetic circuits are growing, but stay limited by a shortage of regulatory parts that can be used without interference. Therefore, orthogonal expression and regulation systems are needed to minimize undesired crosstalk and allow for dynamic control of separate modules. This work presents a set of orthogonal expression systems for use in Escherichia coli based on heterologous sigma factors from Bacillus subtilis that recognize specific promoter sequences. Up to four of the analyzed sigma factors can be combined to function orthogonally between each other and toward the host. Additionally, the toolbox is expanded by creating promoter libraries for three sigma factors without loss of their orthogonal nature. As this set covers a wide range of transcription initiation frequencies, it enables tuning of multiple outputs of the circuit in response to different sensory signals in an orthogonal manner. This sigma factor toolbox constitutes an interesting expansion of the synthetic biology toolbox and may contribute to the assembly of more complex synthetic genetic systems in the future.
S-8129-2019
BACILLUS-SUBTILIS;CELL-ENVELOPE;DESIGN;DIRECTED EVOLUTION;EXTRACYTOPLASMIC-FUNCTION SIGMA(X);IDENTIFICATION;IN-VIVO;PATHWAY;SYNTHETIC BIOLOGY;TRANSCRIPTION
5
null
null
12
BACILLUS-SUBTILIS;cell envelope;DESIGN;directed evolution;EXTRACYTOPLASMIC-FUNCTION SIGMA(X);IDENTIFICATION;IN-VIVO;PATHWAY;Synthetic biology;TRANSCRIPTION
WOS:000426293300048
Univ Ghent, Ghent, Belgium;Vrije Univ Brussel, Brussels, Belgium
Belgium
2,018
null
0000-0002-1402-7517;0000-0002-6844-376X;0000-0002-8134-9436
null
null
English
null
ACS SYNTH BIOL;ANNU REV CHEM BIOMOL;ANNU REV MICROBIOL;BIOENGINEERED;BIOMOLECULES;BIOTECHNOL ADV;BMC BIOTECHNOL;CELL;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;CURR OPIN MICROBIOL;ENZYME MICROB TECH;FRONT PLANT SCI;GENE;J AM CHEM SOC;J BACTERIOL;J BIOTECHNOL;J IND MICROBIOL BIOT;J MOL BIOL;J STAT SOFTW;METAB ENG;MICROB CELL FACT;MICROBIOL MOL BIOL R;MOL MICROBIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT REV GENET;NAT REV MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS COMPUT BIOL;PLOS ONE;SCI REP UK;SCIENCE;TRENDS BIOTECHNOL
Bervoets, Indra;Charlier, Daniel;De Mey, Marjan;Maertens, Jo;Van Brempt, Maarten;Van Hove, Bob;Van Nerom, Katleen
2024-03-11 ER
Ajikumar, P K;Amaya, E;An, W L;Arense, P;Bagyan, I;Bikard, D;Bradley, R W;Brewster, R C;Britton, R A;Browning, D F;Cao, M;Chen, Y F;Cheon, S;Coussement, P;Dagert, M;Datsenko, K A;Davis, J H;De Mey, M;De Paepe, B;Eiamphungporn, W;Errington, J;Green, A A;Grigorova, I L;Gruber, T M;Gu, L;Hengge-Aronis, R;Jones, J A;Jullesson, D;Kahm, M;Kazmierczak, M J;Keasling, J D;Li, G W;Lonetto, M;Lucks, J B;Maeda, H;Meyer, A J;Mitchell, J E;Mutalik, V K;Na, D;Paddon, C J;Paget, M S;Pandey, R P;Petersohn, A;Piggot, P J;Qi, L S;Qiu, J;Quan, J Y;Rhodius, V A;Salis, H M;Segall-Shapiro, T H;Sharma, V;Shimada, T;Shis, D L;Singh, A;Slusarczyk, A L;Stanton, B C;Sun, D X;Tai, M;Temme, K;Trantas, E A;Trubitsyna, M;Tyo, K E J;Van Hove, B;Wang, S T;Wargacki, A J;Werner, S;Woolston, B M;Wu, G;Wu, J J;Xu, P;Zhang, Y W;Zou R.
FX7TG
Brussels, Belgium
66
null
2
null
29,361,130
Bervoets, Indra;Charlier, Daniel;De Mey, Marjan;Maertens, Jo;Van Brempt, Maarten;Van Hove, Bob;Van Nerom, Katleen
NUCLEIC ACIDS RES
Brussels, Belgium;Ghent, Belgium
Wang, X;Wu, F Q;Zhang, Q
10.1016/j.cels.2018.01.010
null
50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
7057195h3de613s6v3q3f1o4q3yq2u5v181e48
Design of Adjacent Transcriptional Regions to Tune Gene Expression and Facilitate Circuit Construction
Arizona State Univ
null
Wang, X (corresponding author), Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA.
null
Wang, Xiao;Wu, Fuqing;Zhang, Qi
Biochemistry & Molecular Biology;Cell Biology
American Heart Association [15PRE25710303]; National Science Foundation [DMS-1100309]; NIH [GM106081]
WOS
Wang, X
Arizona State Univ, Tempe, AZ USA
6
Adjacent;and;circuit;construction;design;expression;Facilitate;gene;of;Regions;to;Transcriptional;tune
1
Wang, Xiao;Wu, Fuqing;Zhang, Qi
CELL PRESS
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA
Article
Arizona State Univ
CAMBRIDGE
null
null
Arizona State Univ
American Heart Association;National Science Foundation;NIH
Wang, X (corresponding author), Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA.
+
Wang, Xiao;Wu, Fuqing;Zhang, Qi
23
1
427,421,500,010
American Heart Association [15PRE25710303];National Science Foundation [DMS-1100309];NIH [GM106081]
USA
CELL SYSTEMS
USA
null
null
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA
2405-4712
Wang, X;Wu, F Q;Zhang, Q
FEB 28
xiaowang@asu.edu
Adjacent Transcriptional Regions;Circuit Construction;gene expression
3
J
Biochemistry & Molecular Biology;Cell Biology
300-fold range;account ATRs;Adjacent Transcriptional Regions;adjacent transcriptional regions (ATR);ATRs;BACTERIA;bistability;Circuit Construction;common;complex synthetic gene circuits;comprehensive model;DEGRADATION;degrees;designed synthetic 5'ATRs;different ATRs;different GC content;ESCHERICHIA-COLI;expression;future engineering;gene expression;genes/noncoding regions;high GC content;high gene expression;high sensitivity;INITIATION;logic gates;low basal expression;low folding energy lead;MESSENGER-RNA;networks;nonlinearity;one gene;operon;ORGANIZATION;polycistronic architecture;protein expression levels;reporter gene;results;secondary structure;sizes;small size;synthetic biology;synthetic gene circuits;synthetic operons;synthetic toggle switches;takes;TRANSLATION EFFICIENCY;unknown;varying basal expression
Wu, F Q
BACTERIA;DEGRADATION;ESCHERICHIA-COLI;INITIATION;MESSENGER-RNA;NETWORKS;ORGANIZATION;SECONDARY STRUCTURE;Synthetic biology;TRANSLATION EFFICIENCY
206
[Wu, Fuqing; Zhang, Qi; Wang, Xiao] Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA.
We thank Dr. Alexander Green for helpful suggestions and comments and Josh Cutts, Wei Feng, and Stefan Tekel for technical support for the RT-qPCR experiments. We would also like to thank Dr. John Fricks for inputs on statistical analysis and reasoning. F.W. was supported by an American Heart Association Predoctoral Fellowship (15PRE25710303). This study was financially supported by a National Science Foundation grant (DMS-1100309) and NIH grant (GM106081) (to X.W.).
300-fold range;account ATRs;adjacent transcriptional regions (ATR);ATRs;bistability;common;complex synthetic gene circuits;comprehensive model;degrees;designed synthetic 5'ATRs;different ATRs;different GC content;expression;future engineering;gene expression;genes/noncoding regions;high GC content;high gene expression;high sensitivity;logic gates;low basal expression;low folding energy lead;nonlinearity;one gene;operon;polycistronic architecture;protein expression levels;reporter gene;results;sizes;small size;synthetic gene circuits;synthetic operons;synthetic toggle switches;takes;unknown;varying basal expression
10.1002/jcc.21596;10.1016/j.cell.2014.10.004;10.1016/j.cell.2016.03.006;10.1016/j.cell.2016.04.059;10.1016/j.cels.2017.06.001;10.1016/j.chembiol.2014.10.008;10.1016/j.jmb.2016.02.018;10.1016/j.jtbi.2008.02.005;10.1016/j.molcel.2016.06.006;10.1021/bi9809425;10.1021/jacs.6b01453;10.1021/sb4000977;10.1038/35002125;10.1038/35002131;10.1038/509S13a;10.1038/nature13238;10.1038/nature18930;10.1038/nbt.1568;10.1038/nbt.3053;10.1038/nbt0509-450;10.1038/nrmicro.2015.24;10.1038/nrmicro2930;10.1073/pnas.0909910107;10.1073/pnas.1105692108;10.1073/pnas.1205693109;10.1073/pnas.1305590110;10.1073/pnas.87.19.7668;10.1093/femsre/fuv022;10.1093/nar/27.7.1578;10.1093/nar/gku159;10.1101/gad.6.1.135;10.1101/gr.912603;10.1126/science.1170160;10.1126/science.1188308;10.1126/science.1209042;10.1126/science.aaa3794;10.1126/science.aac7341;10.1128/AEM.01055-16;10.1146/annurev.genet.42.110807.091653;10.1186/s13036-017-0068-1;10.1371/journal.pone.0113380;10.1371/journal.pone.0176013;10.15252/msb.20134955;10.15252/msb.20145794;10.15252/msb.20156540;10.3184/003685015X14368807556441;10.3389/fmicb.2014.00451;10.7554/eLife.23702;[10.1038/NMETH.2205, 10.1038/nmeth.2205];[10.1038/NMETH.2404, 10.1038/nmeth.2404];[10.1038/NMETH.2926, 10.1038/nmeth.2926];[10.1038/NMETH.3147, 10.1038/nmeth.3147]
Arizona State Univ
Wang, X;Wu, F Q;Zhang, Q
Wu, F Q: Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA
Wang, Xiao;Wu, Fuqing
15PRE25710303;DMS-1100309;GM106081
53
null
USA
Arizona State Univ
Wu, Fuqing
Green Accepted, Bronze
BACTERIA;DEGRADATION;ESCHERICHIA-COLI;INITIATION;MESSENGER-RNA;NETWORKS;ORGANIZATION;SECONDARY STRUCTURE;SYNTHETIC BIOLOGY;TRANSLATION EFFICIENCY
Wu, Fuqing; Zhang, Qi; Wang, Xiao;
null
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA
2405-4720
null
2
1990;1992;1995;1998;1999;2000;2003;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
11
Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA
Cell Syst.
Wang, Xiao
CELL PRESS
(ATR);,;300-fold;5'ATRs;a;account;adjacent;affected;and;architecture;ATRs;basal;based;bistability;build;built;by;circuits;common;complex;comprehensive;construct;constructed;content;could;degrees;design;designed;different;energy;engineering;expression;facilitate;flanked;folding;for;found;furthermore;future;gates;GC;gene;generated;genes/noncoding;here;high;how;however;in;into;is;it;lead;levels;logic;low;metric;model;more;nonlinearity;of;on;one;operon;operons;other;our;over;polycistronic;presence;protein;range;rationally;regions;remains;reporter;results;sensitivity;size;sizes;small;switches;synthetic;takes;termed;that;the;these;to;toggle;transcriptional;tune;unknown;used;varying;we;with
Arizona State Univ
Polycistronic architecture is common for synthetic gene circuits, however, it remains unknown how expression of one gene is affected by the presence of other genes/noncoding regions in the operon, termed adjacent transcriptional regions (ATR). Here, we constructed synthetic operons with a reporter gene flanked by different ATRs, and we found that ATRs with high GC content, small size, and low folding energy lead to high gene expression. Based on these results, we built a model of gene expression and generated a metric that takes into account ATRs. We used the metric to design and construct logic gates with low basal expression and high sensitivity and nonlinearity. Furthermore, we rationally designed synthetic 5'ATRs with different GC content and sizes to tune protein expression levels over a 300-fold range and used these to build synthetic toggle switches with varying basal expression and degrees of bistability. Our comprehensive model and gene expression metric could facilitate the future engineering of more complex synthetic gene circuits.
A-8414-2008;AAU-8942-2021;I-9228-2017
BACTERIA;DEGRADATION;ESCHERICHIA-COLI;INITIATION;MESSENGER-RNA;NETWORKS;ORGANIZATION;SECONDARY STRUCTURE;SYNTHETIC BIOLOGY;TRANSLATION EFFICIENCY
1
null
null
16
ESCHERICHIA-COLI;BACTERIA;DEGRADATION;INITIATION;MESSENGER-RNA;NETWORKS;ORGANIZATION;SECONDARY STRUCTURE;Synthetic biology;TRANSLATION EFFICIENCY
WOS:000427421500010
Arizona State Univ, Tempe, AZ USA
USA
2,018
null
0000-0002-2820-3550;0000-0002-4056-0155;0000-0002-8463-1322
null
null
English
null
ACS SYNTH BIOL;ANNU REV GENET;APPL ENVIRON MICROB;BIOCHEMISTRY-US;CELL;CELL SYST;CHEM BIOL;ELIFE;FEMS MICROBIOL REV;FRONT MICROBIOL;GENE DEV;GENOME RES;J AM CHEM SOC;J Biol Eng;J COMPUT CHEM;J MOL BIOL;J THEOR BIOL;METHOD ENZYMOL;MOL CELL;MOL SYST BIOL;NAT BIOTECHNOL;NAT METHODS;NAT REV MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;SCI PROGRESS-UK;SCIENCE
Wang, Xiao;Wu, Fuqing;Zhang, Qi
2024-03-11 ER
Ahnert, S E;Bennett, M R;Borujeni, A E;Brophy, J A N;Cameron, D E;Cao, Y X L;Carr, S B;Chen, H Y;Chen, Y;Chizzolini, F;Desmit, M H;Din, M O;Egbert, R G;Elowitz, M B;Emory, S A;Farasat, I;Ferreira, J P;Gardner, T S;Kudla, G;Lee, J W;Li, J;Lim, H N;Litcofsky, K D;Liu, C L;Ma, K C;Mackie, G A;Mao, Y H;Mus, F;Mutalik, V K;Nielsen, A A K;Oliva, G;Pardee, K;Prindle, A;Rocha, E P C;Salis, H M;Seffens, W;Selinger, D W;Serra, M J;Smanski, M J;Taniguchi, Y;Trotta, E;Tuller, T;Wright, G;Wu, F Q;Xia, T B;Yang, L;Yeung, E;Zadeh, J N;Zhang, W W
FZ2PG
Tempe, AZ USA
14
null
1
null
29,428,414
Wang, Xiao;Wu, Fuqing;Zhang, Qi
CELL SYST
Tempe, AZ USA
Boehm, C R;Grant, P K;Haseloff, J
10.1038/s41467-018-03069-3
776
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
212c6d51374z485r244682q5m701b2f2k1j2o2r
Programmed hierarchical patterning of bacterial populations
Univ Cambridge
null
Haseloff, J (corresponding author), Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England.
null
Boehm, Christian R;Grant, Paul K;Haseloff, Jim
Multidisciplinary Sciences
Gates Cambridge Trust; John Templeton Foundation [15619]; Biotechnology and Biological Sciences Research Council; Engineering and Physical Sciences Research Council [BB/L014130/1]; EC [612146]; BBSRC [BB/L014130/1] Funding Source: UKRI
WOS
Haseloff, J
Max Planck Inst Mol Plant Physiol, Potsdam, Germany;Microsoft Res, Cambridge, England;Univ Cambridge, Cambridge, England
9
Bacterial;hierarchical;of;patterning;populations;programmed
2
Boehm, Christian R.;Grant, Paul;Haseloff, Jim
NATURE PUBLISHING GROUP
Max Planck Inst Mol Plant Physiol, Muhlenberg 1, D-14476 Potsdam, Germany;Microsoft Res, 21 Stn Rd, Cambridge CB1 2FB, England;Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England
Article
Univ Cambridge
LONDON
null
null
Max Planck Inst Mol Plant Physiol;Microsoft Res;Univ Cambridge
BBSRC;Biotechnology and Biological Sciences Research Council;EC;Engineering and Physical Sciences Research Council;Gates Cambridge Trust;John Templeton Foundation
Haseloff, J (corresponding author), Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England.
null
Boehm, Christian R;Grant, Paul K;Haseloff, Jim
20
3
425,787,500,017
BBSRC [BB/L014130/1] Funding Source: UKRI;Biotechnology and Biological Sciences Research Council;EC [612146];Engineering and Physical Sciences Research Council [BB/L014130/1];Gates Cambridge Trust;John Templeton Foundation [15619]
Germany;UK
NATURE COMMUNICATIONS
UK
null
null
Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England
2041-1723
Boehm, C R;Grant, P K;Haseloff, J
FEB 22
jh295@cam.ac.uk
bacterial populations
3
J
Science & Technology - Other Topics
autonomous induction;bacterial gene expression domains;bacterial populations;bacteriophage T7 RNA polymerase activity;BACTERIOPHAGE-T7;best-performing variant;biological self-organization;cell suspension;control;date;different;dissection;DNA;emulation;expression;fundamental mechanisms shaping morphogenesis;gate-like behavior;gene expression across bacterial populations;gene expression domains;genes;growth;hierarchical induction;importance;IN-VIVO;little attention;membrane-based spatial assay;modern genetic tools;multicellular;multicellular organisms;population-based AND-logic;POSITIONAL INFORMATION;promoters;ratiometric assay;sequence;several synthetic genetic circuits;split enzyme variants;surface culture;synthetic biologists;synthetic circuit;synthetic genetic system;SYSTEM;T7 RNA-POLYMERASE;three-color;two different homoserine lactones
Boehm, C R
BACTERIOPHAGE-T7;DNA;EXPRESSION;GENES;GROWTH;IN-VIVO;POSITIONAL INFORMATION;PROMOTERS;SEQUENCE;T7 RNA-POLYMERASE
null
[Boehm, Christian R.; Grant, Paul K.; Haseloff, Jim] Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England. [Grant, Paul K.] Microsoft Res, 21 Stn Rd, Cambridge CB1 2FB, England. [Boehm, Christian R.] Max Planck Inst Mol Plant Physiol, Muhlenberg 1, D-14476 Potsdam, Germany.
C.R.B. acknowledges support from the Gates Cambridge Trust. P.K.G. acknowledges support from the John Templeton Foundation (Grant No. 15619: "Mind, Mechanism and Mathematics: Turing Centenary Research Project"). J.H. acknowledges support from the Biotechnology and Biological Sciences Research Council and the Engineering and Physical Sciences Research Council (OpenPlant Grant No. BB/L014130/1) and EC FP7 project no. 612146 (PLASWIRES).
autonomous induction;bacterial gene expression domains;bacteriophage T7 RNA polymerase activity;best-performing variant;biological self-organization;cell suspension;control;date;different;dissection;emulation;fundamental mechanisms shaping morphogenesis;gate-like behavior;gene expression across bacterial populations;gene expression domains;hierarchical induction;importance;little attention;membrane-based spatial assay;modern genetic tools;multicellular;multicellular organisms;population-based AND-logic;ratiometric assay;several synthetic genetic circuits;split enzyme variants;surface culture;synthetic biologists;synthetic circuit;synthetic genetic system;system;three-color;two different homoserine lactones
10.1002/dvg.1020090202;10.1006/jmbi.1996.0399;10.1016/0022-2836(86)90385-2;10.1016/0092-8674(79)90097-7;10.1016/0092-8674(89)90103-7;10.1016/0378-1119(87)90165-X;10.1016/B978-0-12-385120-8.00002-4;10.1016/j.cell.2009.04.048;10.1016/j.cell.2009.12.001;10.1016/j.chembiol.2014.10.008;10.1016/S0022-2836(83)80282-4;10.1016/S0022-5193(69)80016-0;10.1021/acssynbio.5b00116;10.1021/acssynbio.5b00286;10.1021/acssynbio.6b00248;10.1021/bi000365w;10.1021/bi00415a055;10.1021/ja907617a;10.1021/sb200015u;10.1021/sb400152n;10.1038/280035a0;10.1038/353031a0;10.1038/msb.2008.24;10.1038/msb.2013.55;10.1038/nature03461;10.1038/nature11516;10.1038/nbt0102-87;10.1038/ncomms1738;10.1038/ncomms5905;10.1038/nrg1837;10.1038/srep15159;10.1073/pnas.0407229101;10.1073/pnas.0704256104;10.1073/pnas.1220157110;10.1073/pnas.92.26.12250;10.1074/jbc.M311194200;10.1093/nar/gkq671;10.1093/nar/gks597;10.1093/nar/gku884;10.1098/rsif.2014.1041;10.1098/rstb.1952.0012;10.1101/cshperspect.a001990;10.1101/cshperspect.a023929;10.1103/PhysRevLett.94.018103;10.1126/science.aaa3794;10.1128/JB.132.2.734-737.1977;10.1128/jb.174.2.619-622.1992;10.1128/jb.177.6.1497-1504.1995;10.1128/jb.179.2.557-562.1997;10.1146/annurev-genet-102108-134304;10.1186/1754-1611-3-10;10.1242/dev.114991;10.1371/journal.pbio.0030064;10.15252/msb.20145299;10.15252/msb.20156590;10.3389/fbioe.2015.00030;[10.1038/NMETH.1318, 10.1038/nmeth.1318];[10.1038/NMETH.2019, 10.1038/nmeth.2019]
Univ Cambridge
Boehm, C R;Grant, P K;Haseloff, J
Boehm, C R: Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England
null
15619;612146;BB/L014130/1
60
null
UK
Max Planck Inst Mol Plant Physiol;Microsoft Res;Univ Cambridge
Boehm, Christian R
gold, Green Published, Green Submitted
BACTERIOPHAGE-T7;DNA;EXPRESSION;GENES;GROWTH;IN-VIVO;POSITIONAL INFORMATION;PROMOTERS;SEQUENCE;T7 RNA-POLYMERASE
Boehm, Christian R.; Grant, Paul K.; Haseloff, Jim;
null
Max Planck Inst Mol Plant Physiol, Muhlenberg 1, D-14476 Potsdam, Germany;Microsoft Res, 21 Stn Rd, Cambridge CB1 2FB, England;Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England
Max Planck Inst Mol Plant Physiol, Muhlenberg 1, D-14476 Potsdam, Germany;Microsoft Res, 21 Stn Rd, Cambridge CB1 2FB, England;Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England
null
null
null
1952;1969;1977;1979;1983;1986;1987;1988;1989;1991;1992;1995;1996;1997;2000;2002;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
25
Univ Cambridge, Dept Plant Sci, Downing St, Cambridge CB2 3EA, England
Nat. Commun.
Haseloff, Jim
NATURE PUBLISHING GROUP
,;a;across;activity;allow;and;AND-logic;assay;attention;autonomous;bacterial;bacteriophage;been;behavior;best-performing;biological;biologists;both;build;cell;characterize;circuit;circuits;control;culture;date;demonstrate;despite;develop;different;dissection;domains;emulation;enzyme;expression;finally;for;from;fundamental;gate-like;gene;genetic;has;have;here;hierarchical;homoserine;however;implementing;importance;in;induction;intact;it;its;lactones;little;mechanisms;membrane-based;modern;morphogenesis;multicellular;of;organisms;patterning;polymerase;population-based;populations;programmed;ratiometric;received;report;reported;responsive;RNA;self-organization;several;shaping;spatial;split;surface;suspension;synthetic;system;systematically;T7;the;then;this;three-color;to;tools;two;use;utilize;validate;variant;variants;we
Univ Cambridge
Modern genetic tools allow the dissection and emulation of fundamental mechanisms shaping morphogenesis in multicellular organisms. Several synthetic genetic circuits for control of multicellular patterning have been reported to date. However, hierarchical induction of gene expression domains has received little attention from synthetic biologists, despite its importance in biological self-organization. Here we report a synthetic genetic system implementing population-based AND-logic for programmed autonomous induction of bacterial gene expression domains. We develop a ratiometric assay for bacteriophage T7 RNA polymerase activity and use it to systematically characterize different intact and split enzyme variants. We then utilize the best-performing variant to build a three-color patterning system responsive to two different homoserine lactones. We validate the AND gate-like behavior of this system both in cell suspension and in surface culture. Finally, we use the synthetic circuit in a membrane-based spatial assay to demonstrate programmed hierarchical patterning of gene expression across bacterial populations.
null
BACTERIOPHAGE-T7;DNA;EXPRESSION;GENE;GROWTH;IN-VIVO;POSITIONAL INFORMATION;PROMOTER;SEQUENCE;T7 RNA-POLYMERASE
0
null
null
10
BACTERIOPHAGE-T7;DNA;EXPRESSION;GENE;GROWTH;IN-VIVO;POSITIONAL INFORMATION;PROMOTER;SEQUENCE;T7 RNA-POLYMERASE
WOS:000425787500017
Max Planck Inst Mol Plant Physiol, Potsdam, Germany;Microsoft Res, Cambridge, England;Univ Cambridge, Cambridge, England
Germany;UK
2,018
null
0000-0002-1099-0461;0000-0002-6633-7998;0000-0003-4793-8058
null
null
English
null
ACS SYNTH BIOL;ANNU REV GENET;BIOCHEMISTRY-US;CELL;CHEM BIOL;CSH PERSPECT BIOL;DEV GENET;DEVELOPMENT;FRONT BIOENG BIOTECH;GENE;J AM CHEM SOC;J BACTERIOL;J BIOL CHEM;J Biol Eng;J MOL BIOL;J R SOC INTERFACE;J THEOR BIOL;Mechanisms of Morphogenesis;METHOD ENZYMOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT COMMUN;NAT METHODS;NAT REV GENET;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHILOS T ROY SOC B;PHYS REV LETT;PLOS BIOL;SCI REP-UK;SCIENCE
Boehm, Christian R;Grant, Paul K;Haseloff, Jim
2024-03-11 ER
Balagadde, F K;Barkai, N;Basu, S;Bollenbach, T;Brenner, K;Chen, Y;Coen, E S;Cohen, S N;Davies Jamie A.;Davis, R M;Dong, H J;Dunn, J J;Gibson, D G;Goedhart, J;Grant, P K;Greber, D;Green, J B A;Han, T Y;Haughn, G W;Ikeda, R A;Imburgio, D;Iost, I;Isalan, M;Kimelman, D;Klumpp, S;Lo, W C;Makarova, O V;Miroux, B;Moon, T S;Muller, D K;Nagai, T;Ng, W L;Panayotatos, N;Payne, S;Reinke, A W;Rosa, M D;Rosenberg, A H;Rudge, T J;Salis, H M;Schaerli, Y;Schindelin, J;Schuster, M;Scott, S R;Segall-Shapiro, T H;Shis, D L;Sohka Takayuki;Sternberg, P W;Stevens, A M;Studier, F W;Tabor, J J;Teague, B P;Temme, K;Thompson, K E;Turing, A M;Wang, L H;Wang, L Y;Wolpert, L;Wu, F Q;Yordanov, B
FX1DE
Cambridge, England
27
null
3
null
29,472,537
Boehm, Christian R;Grant, Paul K;Haseloff, Jim
NAT COMMUN
Cambridge, England;Potsdam, Germany
Cole, C M;Devaraj, N K;Joseph, S;Shi, X Y;Wu, T
10.1038/s41598-018-21739-6
3488
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
1x6x4c55t5l6t6c4ye1q5t3n3s4p6p57554y3q
Optimization of ClpXP activity and protein synthesis in an <i>E-coli</i> extract-based cell-free expression system
Univ Calif San Diego
null
Joseph, S (corresponding author), Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA.
null
Cole, Christian M;Devaraj, Neal K;Joseph, Simpson;Shi, Xinying;Wu, Ti
Multidisciplinary Sciences
Department of Defense Army Research Office [W911NF-13-1-0383]
WOS
Joseph, S
Univ Calif San Diego, La Jolla, CA USA
8
<i>E-coli</i>;activity;an;and;Cell-Free;ClpXP;expression;extract-based;in;of;optimization;protein;synthesis;system
1
Wu, Ti
NATURE PUBLISHING GROUP
Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA
Article
Univ Calif San Diego
LONDON
null
null
Univ Calif San Diego
Department of Defense Army Research Office
Joseph, S (corresponding author), Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA.
null
Cole, Christian M;Devaraj, Neal K;Joseph, Simpson;Shi, Xinying;Wu, Ti
17
1
425,728,600,044
Department of Defense Army Research Office [W911NF-13-1-0383]
USA
SCIENTIFIC REPORTS
USA
null
null
Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA
2045-2322
Cole, C M;Devaraj, N K;Joseph, S;Shi, X Y;Wu, T
FEB 22
sjoseph@ucsd.edu
<i>E-coli</i> extract-based cell-free expression system;ClpXP activity;optimization;protein synthesis
5
J
Science & Technology - Other Topics
<i>E-coli</i> extract-based cell-free expression system;activity;adenosine triphosphate (ATP);ATP;cell;cell extract;cell-free expression system;cell-free transcription-translation (TX-TL) systems;ClpXP;ClpXP activity;conditions;damaged proteins;DEGRADATION MACHINE;E. coli ClpXP protease;efficient protein expression platform;EMULSION;energy regeneration system;established conditions;exogenous ATP;function;fundamental process;IN-VITRO;intact proteins;living cells;low activity;low proteolytic activity;optimization;POLYPHOSPHATE;protein degradation;protein synthesis;purified ClpXP;rapid consumption;robust protein degradation system;SSPB ADAPTER;studies;synthetic;tunable synthetic genetic circuits;TX-TL system;TX-TL systems;used E. coli S30 cell extract;VESICLES;vitro synthetic biology;will
Shi, X Y
ATP;DEGRADATION MACHINE;EMULSION;IN-VITRO;POLYPHOSPHATE;SSPB ADAPTER;VESICLES
null
[Shi, Xinying; Wu, Ti; Cole, Christian M.; Devaraj, Neal K.; Joseph, Simpson] Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA.
This work was supported by the Department of Defense Army Research Office contract W911NF-13-1-0383.
activity;adenosine triphosphate (ATP);cell;cell extract;cell-free expression system;cell-free transcription-translation (TX-TL) systems;ClpXP;ClpXP activity;conditions;damaged proteins;E. coli ClpXP protease;efficient protein expression platform;energy regeneration system;established conditions;exogenous ATP;function;fundamental process;intact proteins;living cells;low activity;low proteolytic activity;protein degradation;protein synthesis;purified ClpXP;rapid consumption;robust protein degradation system;studies;synthetic;tunable synthetic genetic circuits;TX-TL system;TX-TL systems;used E. coli S30 cell extract;vitro synthetic biology;will
10.1002/cbic.201500643;10.1016/0005-2760(74)90091-5;10.1016/B978-0-12-420067-8.00025-8;10.1016/j.bbamcr.2011.06.007;10.1016/j.cell.2009.09.034;10.1016/j.jmb.2015.06.021;10.1016/j.mimet.2005.05.003;10.1016/j.molcel.2004.10.001;10.1016/j.tibs.2016.08.013;10.1016/S0092-8674(00)80431-6;10.1016/S0092-8674(03)00612-3;10.1016/S1097-2765(00)80243-9;10.1016/S1097-2765(03)00060-1;10.1021/acssynbio.5b00296;10.1021/la026100v;10.1038/35002125;10.1038/nature13238;10.1073/pnas.1600098113;10.1073/pnas.1931005100;10.1074/jbc.M109.017624;10.1088/1478-3975/2/3/P01;10.1093/nar/gkh925;10.1101/gad.12.9.1338;10.1101/gad.1240104;10.1126/science.289.5488.2354;10.1128/AEM.66.5.2045-2051.2000;10.1146/annurev-biochem-060408-172623;10.1186/1754-1611-4-8;10.1186/1754-1611-4-9;10.1371/journal.pone.0028707
Univ Calif San Diego
Cole, C M;Devaraj, N K;Joseph, S;Shi, X Y;Wu, T
Shi, X Y: Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA
Devaraj, Neal K
W911NF-13-1-0383
31
null
USA
Univ Calif San Diego
Shi, Xinying
gold, Green Published
ATP;DEGRADATION MACHINE;EMULSION;IN-VITRO;POLYPHOSPHATE;SSPB ADAPTER;VESICLES
Shi, Xinying; Wu, Ti; Cole, Christian M.; Devaraj, Neal K.; Joseph, Simpson;
null
Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA
Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA
null
null
null
1974;1997;1998;2000;2003;2004;2005;2006;2009;2010;2011;2012;2013;2014;2015;2016
9
Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA
Sci Rep
Joseph, Simpson
NATURE PUBLISHING GROUP
(ATP);(TX-TL);,;a;activity;added;adding;adenosine;all;also;an;and;are;ATP;be;biology;both;but;by;cell;cell-free;cells;circuits;ClpXP;coli;conditions;consumption;correlated;creating;damaged;degradation;E.;efficient;energy;essential;established;exogenous;expression;extract;for;function;fundamental;genetic;has;improved;in;intact;interested;is;living;longer;low;needed;no;not;occur;of;only;optimized;our;platform;process;protease;protein;proteins;proteolytic;purified;rapid;regeneration;remove;require;robust;S30;showed;simultaneously;studies;surprisingly;synthesis;synthetic;system;systems;tested;that;the;then;therefore;this;to;transcription-translation;triphosphate;tunable;TX-TL;used;useful;very;vitro;was;we;will;with
Univ Calif San Diego
Protein degradation is a fundamental process in all living cells and is essential to remove both damaged proteins and intact proteins that are no longer needed by the cell. We are interested in creating synthetic genetic circuits that function in a cell-free expression system. This will require not only an efficient protein expression platform but also a robust protein degradation system in cell extract. Therefore, we purified and tested the activity of E. coli ClpXP protease in cell-free transcription-translation (TX-TL) systems that used E. coli S30 cell extract. Surprisingly, our studies showed that purified ClpXP added to the TX-TL system has very low proteolytic activity. The low activity of ClpXP was correlated with the rapid consumption of adenosine triphosphate (ATP) in cell extract. We improved the activity of ClpXP in cell extract by adding exogenous ATP and an energy regeneration system. We then established conditions for both protein synthesis, and protein degradation by ClpXP to occur simultaneously in the TX-TL systems. The optimized conditions for ClpXP activity will be useful for creating tunable synthetic genetic circuits and in vitro synthetic biology.
B-4712-2014
ATP;DEGRADATION MACHINE;EMULSION;IN-VITRO;POLYPHOSPHATE;SSPB ADAPTER;VESICLES
1
null
null
11
ATP;DEGRADATION MACHINE;EMULSION;IN-VITRO;POLYPHOSPHATE;SSPB ADAPTER;VESICLES
WOS:000425728600044
Univ Calif San Diego, La Jolla, CA USA
USA
2,018
null
0000-0001-6427-6418
null
null
English
null
ACS SYNTH BIOL;ANNU REV BIOCHEM;APPL ENVIRON MICROB;BBA-MOL CELL RES;BIOCHIM BIOPHYS ACTA;BioRxiv;CELL;CHEMBIOCHEM;GENE DEV;J BIOL CHEM;J Biol Eng;J MICROBIOL METH;J MOL BIOL;LANGMUIR;METHOD ENZYMOL;MOL CELL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS BIOL;PLOS ONE;SCIENCE;TRENDS BIOCHEM SCI
Cole, Christian M;Devaraj, Neal K;Joseph, Simpson;Shi, Xinying;Wu, Ti
2024-03-11 ER
Baker, T A;Bolon, D N;Chowdhuri, S;Davis, J H;Elowitz, M B;Flynn, J M;Garamella, J;Ge, X M;Glynn, S E;Gottesman, S;Itoh, H;Jendrasi.Gl;Kenniston, J A;Kim, Y I;Levchenko, I;Noireaux, V;Pautot, S;Pontes, M H;Prindle, A;Rajagopal, V;Resnick, S M;Rivas, G;Sauer, R T;Sharp, K A;Shin Jonghyeon;Sun Z.Z.;Thompson, J;Wang, J M
FX0JF
La Jolla, CA USA
12
null
1
null
29,472,573
Cole, Christian M;Devaraj, Neal K;Joseph, Simpson;Shi, Xinying;Wu, Ti
SCI REP-UK
La Jolla, CA USA
de Lange, O;Klavins, E;Nemhauser, J
10.1016/j.copbio.2017.07.003
null
THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
30336g6a6wg3f586a47491h1p3g5v6q2r2n4o3c
Synthetic genetic circuits in crop plants
Univ Washington
null
Nemhauser, J (corresponding author), Univ Washington, Dept Biol, Seattle, WA 98195 USA.
null
de Lange, Orlando;Klavins, Eric;Nemhauser, Jennifer
Biochemical Research Methods;Biotechnology & Applied Microbiology
National Science Foundation [MCB-1411949]; National Institutes of Health [R01-GM107084]; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1411949] Funding Source: National Science Foundation; Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [1317694] Funding Source: National Science Foundation
WOS
Nemhauser, J
Univ Washington, Seattle, WA USA
49
circuits;crop;genetic;in;plants;synthetic
1
Klavins, Eric
ELSEVIER SCI LTD
Univ Washington, Dept Biol, Seattle, WA 98195 USA;Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA
Review
Univ Washington
OXFORD
null
null
Univ Washington
Direct For Biological Sciences;Direct For Computer & Info Scie & Enginr;Div Of Molecular and Cellular Bioscience;Division of Computing and Communication Foundations;National Institutes of Health;National Science Foundation
Nemhauser, J (corresponding author), Univ Washington, Dept Biol, Seattle, WA 98195 USA.
22
de Lange, Orlando;Klavins, Eric;Nemhauser, Jennifer
35
2
426,224,300,005
Direct For Biological Sciences;Direct For Computer & Info Scie & Enginr;Div Of Molecular and Cellular Bioscience [1411949] Funding Source: National Science Foundation;Division of Computing and Communication Foundations [1317694] Funding Source: National Science Foundation;National Institutes of Health [R01-GM107084];National Science Foundation [MCB-1411949]
USA
CURRENT OPINION IN BIOTECHNOLOGY
USA
null
null
Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA
0958-1669
de Lange, O;Klavins, E;Nemhauser, J
FEB
jn7@uw.edu
crop plants;synthetic genetic circuits
3
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
AGROBACTERIUM-MEDIATED TRANSFORMATION;ARABIDOPSIS;century;coding DNA;combinations;complex traits;considerable barrier;CONSTRUCTION;continued;crop breeding;crop improvement;crop plant;crop plants;desired function;ENRICHMENT;exploratory laboratory testing;future developments necessary;Genetic circuits;genetics;genome;genome modifications;interest;love affair;mass selection programs;mutagenesis;promoters;recent development;requisite DNA parts;RICE;STACKING;standardized pipeline;successes;synthetic genetic circuits;technologies;TRANSGENE EXPRESSION;transgenic products;trials;viable crop improvement technology
de Lange, O
AGROBACTERIUM-MEDIATED TRANSFORMATION;ARABIDOPSIS;CONSTRUCTION;ENRICHMENT;mutagenesis;PROMOTERS;RICE;STACKING;TECHNOLOGIES;TRANSGENE EXPRESSION
16
[de Lange, Orlando; Klavins, Eric] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. [Nemhauser, Jennifer] Univ Washington, Dept Biol, Seattle, WA 98195 USA.
Funding for plant synthetic biology in the Klavins and Nemhauser groups is provided by collaborative grants from the National Science Foundation (MCB-1411949) and the National Institutes of Health (R01-GM107084). JLN is also supported in this work as an HHMI faculty scholar. The authors would like to thank A Lanctot, C Wright and L Adam for critical reading of the manuscript.
century;coding DNA;combinations;complex traits;considerable barrier;continued;crop breeding;crop improvement;crop plant;desired function;exploratory laboratory testing;future developments necessary;genetic circuits;genetics;genome;genome modifications;interest;love affair;mass selection programs;recent development;requisite DNA parts;standardized pipeline;successes;synthetic genetic circuits;transgenic products;trials;viable crop improvement technology
10.1002/biot.201100487;10.1007/s00412-013-0403-3;10.1007/s11032-005-4929-9;10.1007/s11103-011-9767-z;10.1007/s11105-008-0044-5;10.1007/s11627-012-9459-7;10.1016/j.cell.2016.01.011;10.1016/j.copbio.2015.10.001;10.1016/j.copbio.2015.11.007;10.1016/j.pbi.2014.02.004;10.1016/j.tibtech.2011.02.003;10.1016/j.tibtech.2014.12.010;10.1016/j.tplants.2008.09.004;10.1017/S1742170515000198;10.1038/35002125;10.1038/35002131;10.1038/514S55a;10.1038/nature13776;10.1038/nbt.1506;10.1038/nbt.2467;10.1038/nbt1082;10.1038/nprot.2007.241;10.1073/pnas.0809737105;10.1093/jxb/eru138;10.1093/mp/ssu107;10.1093/pcp/pcw201;10.1098/rstb.2007.2170;10.1101/gr.145557.112;10.1104/pp.119.1.133;10.1104/pp.123.3.895;10.1104/pp.15.01542;10.1104/pp.15.01663;10.1105/tpc.010412;10.1111/j.1365-313X.2012.04916.x;10.1111/j.1467-7652.2003.00061.x;10.1111/j.1467-7652.2010.00577.x;10.1111/pbi.12107;10.1111/pbi.12176;10.1111/pbi.12242;10.1111/tpj.12356;10.1126/science.aac7341;10.1186/1754-6834-5-84;10.1186/s40064-015-1369-9;10.1371/journal.pgen.0030179;10.1371/journal.pone.0000350;10.3389/fpls.2014.00169;10.3389/fpls.2016.01949;10.3390/v7082819;10.3791/52189;10.7554/eLife.13664;[10.1038/NMETH.2918, 10.1038/nmeth.2918];[10.1038/NMETH.3659, 10.1038/nmeth.3659]
Univ Washington
de Lange, O;Klavins, E;Nemhauser, J
de Lange, O: Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA
null
1317694;1411949;MCB-1411949;R01-GM107084
55
null
USA
Univ Washington
de Lange, Orlando
hybrid, Green Accepted
AGROBACTERIUM-MEDIATED TRANSFORMATION;ARABIDOPSIS;CONSTRUCTION;ENRICHMENT;MUTAGENESIS;PROMOTERS;RICE;STACKING;TECHNOLOGIES;TRANSGENE EXPRESSION
de Lange, Orlando; Klavins, Eric; Nemhauser, Jennifer;
null
Univ Washington, Dept Biol, Seattle, WA 98195 USA;Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA
Univ Washington, Dept Biol, Seattle, WA 98195 USA;Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA
1879-0429
null
null
1999;2000;2002;2004;2005;2007;2008;2009;2011;2012;2013;2014;2015;2016;2017
29
Univ Washington, Dept Biol, Seattle, WA 98195 USA
Curr. Opin. Biotechnol.
Nemhauser, Jennifer
ELSEVIER SCI LTD
,;a;accelerate;achieve;affair;ago;allowing;and;are;barrier;be;began;between;breeding;bringing;century;circuits;coding;combinations;complex;considerable;continued;could;crop;delivered;designed;desired;development;developments;directly;DNA;exploratory;far;from;function;future;genetic;genetics;genome;has;highlight;however;improvement;interest;into;introduced;is;laboratory;love;make;market;mass;modifications;necessary;not;of;over;parts;pipeline;plant;products;programs;rationally;recent;regulatory;remains;requisite;selection;so;standardized;successes;synthetic;targeted;technology;testing;the;there;this;to;traits;transgenic;trials;unabated;viable;we;yet
Univ Washington
The love affair between crop breeding and genetics began over a century ago and has continued unabated, from mass selection programs to targeted genome modifications. Synthetic genetic circuits, a recent development, are combinations of regulatory and coding DNA introduced into a crop plant to achieve a desired function. Genetic circuits could accelerate crop improvement, allowing complex traits to be rationally designed and requisite DNA parts delivered directly into a genome of interest. However, there is not yet a standardized pipeline from exploratory laboratory testing to crop trials, and bringing transgenic products to market remains a considerable barrier. We highlight successes so far and future developments necessary to make genetic circuits a viable crop improvement technology over this century.
null
AGROBACTERIUM-MEDIATED TRANSFORMATION;ARABIDOPSIS;CONSTRUCTION;ENRICHMENT;MUTAGENESIS;PROMOTER;RICE;STACKING;TECHNOLOGIES;TRANSGENE EXPRESSION
1
null
null
7
AGROBACTERIUM-MEDIATED TRANSFORMATION;ARABIDOPSIS;CONSTRUCTION;ENRICHMENT;mutagenesis;PROMOTER;RICE;STACKING;TECHNOLOGIES;TRANSGENE EXPRESSION
WOS:000426224300005
Univ Washington, Seattle, WA USA
USA
2,018
null
0000-0002-3805-5117
null
null
English
null
BIOTECHNOL BIOFUELS;BIOTECHNOL J;CELL;CHROMOSOMA;CURR OPIN BIOTECH;CURR OPIN PLANT BIOL;ELIFE;FRONT PLANT SCI;GENOME RES;IN VITRO CELL DEV-PL;J EXP BOT;JOVE-J VIS EXP;MOL BREEDING;MOL PLANT;NAT;NAT BIOTECHNOL;NAT METHODS;NAT PROTOC;NATURE;P NATL ACAD SCI USA;PHILOS T R SOC B;PLANT BIOTECHNOL J;PLANT CELL;PLANT CELL PHYSIOL;PLANT J;PLANT MOL BIOL;PLANT MOL BIOL REP;PLANT PHYSIOL;PLOS GENET;PLOS ONE;RENEW AGR FOOD SYST;REVOLUTION FARM TRAN;SCIENCE;SPRINGERPLUS;TRENDS BIOTECHNOL;TRENDS PLANT SCI;VIRUSES-BASEL
de Lange, Orlando;Klavins, Eric;Nemhauser, Jennifer
2024-03-11 ER
Ainley, W M;Bastaki, N K;Birchler, J A;Brouwer, B O;Butaye, K M J;Butelli, E;Carlson, S R;Cermak T.;Clarke, J L;Collard, B C Y;Conkin Paul K.;Delmans, M;Desfeux, C;Diretto, G;Eisenstein, M;Elowitz, M B;Endo, M;Fossati, E;Fuentes, P;Gaeta, R T;Gardner, T S;Hou, L L;Ishida, Y;Kanevski, I;Kosuri, S;Kwit, C;Lin, M T;Liu, W S;Liu, X J;Llorca, C M;Lombardo, L;Lucht, J M;Morey, K J;Nandy, S;Nelissen, H;Nielsen, A A K;Nishizawa-Yokoi, A;Paine, J A;Pardey, P;Patron, N J;Petersen, P D;Qi, Y P;Roybal, K T;Rushton, P J;Scharff, L B;Schaumberg, K A;Srivastava, V;Wang, C;Wijnker, E;Xu, C H;Yadava, P;Yasmeen, A;Zhu, C F;Zuniga-Soto, E
FX6VB
Seattle, WA USA
31
null
1
null
28,772,191
de Lange, Orlando;Klavins, Eric;Nemhauser, Jennifer
CURR OPIN BIOTECH
Seattle, WA USA
Chang, C C;Chen, B S;Liao, W X;Lin, L J;Ling, C;Liu, B;Xie, Z
10.1021/acssynbio.7b00134
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
343m5k6u4n3e5z5y111314hqs3w6r5t2x5v4j
Functional Characterization of Insulation Effect for Synthetic Gene Circuits in Mammalian Cells
Tsinghua Univ
null
Xie, Z (corresponding author), Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China.
null
Chang, Chih-Chun;Chen, Bor-Sen;Liao, Weixi;Lin, Ling-Jun;Ling, Che;Liu, Bing;Xie, Zhen
Biochemical Research Methods
Cross-strait Tsinghua Foundation; National Key Basic Research Program of China [2014CB745200]; Basic Research Program of Tsinghua National Lab for Information Science and Technology; National Science Council [NSC 98-221-E-007-113-MY3]
WOS
Xie, Z
Natl Tsing Hua Univ, Hsinchu, Taiwan;Syngentech Inc, Beijing, Peoples R China;Tsinghua Univ, Beijing, Peoples R China
7
Cells;characterization;circuits;effect;for;functional;gene;in;Insulation;mammalian;of;synthetic
2
null
AMER CHEMICAL SOC
Natl Tsing Hua Univ, Dept Elect Engn, Hsinchu 30013, Taiwan;Syngentech Inc, Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China;Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China
Article
Tsinghua Univ
WASHINGTON
null
null
Natl Tsing Hua Univ;Syngentech Inc;Tsinghua Univ
Basic Research Program of Tsinghua National Lab for Information Science and Technology;Cross-strait Tsinghua Foundation;National Key Basic Research Program of China;National Science Council
Xie, Z (corresponding author), Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China.
418
Chang, Chih-Chun;Chen, Bor-Sen;Liao, Weixi;Lin, Ling-Jun;Ling, Che;Liu, Bing;Xie, Zhen
16
3
426,012,600,014
Basic Research Program of Tsinghua National Lab for Information Science and Technology;Cross-strait Tsinghua Foundation;National Key Basic Research Program of China [2014CB745200];National Science Council [NSC 98-221-E-007-113-MY3]
China;Taiwan
ACS SYNTHETIC BIOLOGY
China
null
null
Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China
2161-5063
Chang, C C;Chen, B S;Liao, W X;Lin, L J;Ling, C;Liu, B;Xie, Z
FEB
zhenxie@tsinghua.edu.cn
functional Characterization;Insulation Effect;mammalian cells;synthetic gene circuits
7
J
Biochemistry & Molecular Biology
affected;BETA-GLOBIN INSULATOR;BIOLOGY;block interference across different chromatin domains;cascade;cascade circuit;chromatin partitioning boundaries;cross-regulations;CTCF;deviation;different cassettes;effect;ENHANCER-BLOCKING ACTIVITY;episomal plasmid vectors;episomal synthetic gene circuits;eukaryotic genome;expression;first regulatory;function;functional Characterization;functional effect;general guide;Insulation Effect;insulators;mammalian cells;modular construction;multiple transcription cassettes;noncoding gene regulatory elements;promoters;quantitative method;response curve;response intensity;results;SELECTION;sensory switch circuit;sensory switch circuits;six promoters;synthetic gene;synthetic gene circuits;three insulators;threshold position;threshold-like effect;unwanted cross-regulations;varying promoters
Liao, W X
BETA-GLOBIN INSULATOR;BIOLOGY;CTCF;ENHANCER-BLOCKING ACTIVITY;EXPRESSION
412
[Liao, Weixi; Xie, Zhen] Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China. [Liu, Bing] Syngentech Inc, Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China. [Chang, Chih-Chun; Lin, Ling-Jun; Ling, Che; Chen, Bor-Sen] Natl Tsing Hua Univ, Dept Elect Engn, Hsinchu 30013, Taiwan.
We thank members of Xie lab for helpful discussions. We thank Yun Jiang and Huiya Huang for technical support. We thank Xiaowo Wang for insightful discussions. The research was supported by the Cross-strait Tsinghua Foundation (Z.X.), the National Key Basic Research Program of China (2014CB745200), the Basic Research Program of Tsinghua National Lab for Information Science and Technology, and the National Science Council (B.C., NSC 98-221-E-007-113-MY3).
affected;block interference across different chromatin domains;cascade;cascade circuit;chromatin partitioning boundaries;cross-regulations;deviation;different cassettes;effect;episomal plasmid vectors;episomal synthetic gene circuits;eukaryotic genome;first regulatory;function;functional effect;general guide;insulation effect;insulators;mammalian cells;modular construction;multiple transcription cassettes;noncoding gene regulatory elements;promoters;quantitative method;response curve;response intensity;results;selection;sensory switch circuit;sensory switch circuits;six promoters;synthetic gene;three insulators;threshold position;threshold-like effect;unwanted cross-regulations;varying promoters
10.1016/j.gde.2011.12.007;10.1016/S0092-8674(00)81967-4;10.1021/sb500263b;10.1038/emboj.2011.406;10.1038/msb.2011.49;10.1038/nbt.2355;10.1038/nbt.2401;10.1038/nbt957;10.1038/nrm3738;10.1038/nrmicro3140;10.1038/sj.mt.6300399;10.1073/pnas.0402938101;10.1073/pnas.1413896112;10.1073/pnas.94.2.575;10.1073/pnas.96.25.14354;10.1089/hgtb.2012.152;10.1093/nar/gkt605;10.1126/science.1140871;10.1126/science.1205527;10.1139/O10-111;10.1146/annurev-chembioeng-061010-114145
Tsinghua Univ
Chang, C C;Chen, B S;Liao, W X;Lin, L J;Ling, C;Liu, B;Xie, Z
Liao, W X: Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China
Chen, Bor-Sen;Xie, Zhen
2014CB745200;NSC 98-221-E-007-113-MY3
23
null
China
Natl Tsing Hua Univ;Syngentech Inc;Tsinghua Univ
Liao, Weixi
null
BETA-GLOBIN INSULATOR;BIOLOGY;CTCF;ENHANCER-BLOCKING ACTIVITY;EXPRESSION
Liao, Weixi; Liu, Bing; Chang, Chih-Chun; Lin, Ling-Jun; Ling, Che; Chen, Bor-Sen; Xie, Zhen;
null
Natl Tsing Hua Univ, Dept Elect Engn, Hsinchu 30013, Taiwan;Syngentech Inc, Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China;Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China
Natl Tsing Hua Univ, Dept Elect Engn, Hsinchu 30013, Taiwan;Syngentech Inc, Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China;Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China
null
null
2
1997;1999;2004;2007;2008;2010;2011;2012;2013;2014;2015
3
Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Dept Automat,MOE Key Lab Bioinformat & Bioinforma, Beijing 100084, Peoples R China
ACS Synth. Biol.
Xie, Zhen
AMER CHEMICAL SOC
,;a;across;affected;along;and;are;as;assembled;avoided;be;between;block;both;boundaries;but;cascade;cassettes;cells;characterize;chromatin;circuit;circuits;composed;construction;context;cross-regulations;curve;developed;deviation;different;displayed;domains;effect;elements;episomal;eukaryotic;facilitate;first;function;functional;gene;general;genome;guide;here;in;insulation;insulators;intensity;interference;is;layer;mainly;mammalian;may;method;modular;multiple;noncoding;not;observed;of;on;or;our;partitioning;plasmid;position;promoters;provided;quantitative;reduce;regulatory;response;results;revealed;selection;sensory;should;showed;six;some;switch;synthetic;tested;that;the;therefore;three;threshold;threshold-like;to;transcription;unwanted;useful;usually;varied;varying;vectors;was;we;were;which;with;without
Tsinghua Univ
Insulators are noncoding gene regulatory elements in eukaryotic genome, which function as chromatin partitioning boundaries, and block interference across different chromatin domains. To facilitate modular construction of synthetic gene circuit that is usually composed of multiple transcription cassettes, unwanted cross-regulations between different cassettes should be avoided. Here, we developed a quantitative method to characterize the functional effect of three insulators on the cross-regulations of six promoters in mammalian cells. We showed that the unwanted cross-regulations displayed a threshold-like effect, and the threshold position varied along with the context of promoters and insulators. We tested the function of insulators in both cascade and sensory switch circuits assembled in episomal plasmid vectors, and showed that the insulation effect was mainly revealed on the first regulatory layer of the cascade circuit. A deviation on the response curve of the sensory switch circuit with or without insulators was observed, but response intensity of some sensory switch circuits were not affected. Therefore, our results provided a general guide on the selection of insulators with varying promoters in episomal synthetic gene circuits in mammalian cells, which may be useful to reduce the effect of the unwanted cross-regulations.
D-9114-2017;GPW-5925-2022
BETA-GLOBIN INSULATOR;BIOLOGY;CTCF;ENHANCER-BLOCKING ACTIVITY;EXPRESSION
1
null
null
13
BETA-GLOBIN INSULATOR;BIOLOGY;CTCF;ENHANCER-BLOCKING ACTIVITY;EXPRESSION
WOS:000426012600014
Natl Tsing Hua Univ, Hsinchu, Taiwan;Syngentech Inc, Beijing, Peoples R China;Tsinghua Univ, Beijing, Peoples R China
China;Taiwan
2,018
null
null
null
null
English
null
ACS SYNTH BIOL;ANNU REV CHEM BIOMOL;BIOCHEM CELL BIOL;CELL;CURR OPIN GENET DEV;EMBO J;HUM GENE THER METHOD;MOL SYST BIOL;MOL THER;NAT BIOTECHNOL;NAT CHEM BIOL;NAT REV MICROBIOL;NAT REV MOL CELL BIO;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;REV CELL BIOL MOL ME;SCIENCE
Chang, Chih-Chun;Chen, Bor-Sen;Liao, Weixi;Lin, Ling-Jun;Ling, Che;Liu, Bing;Xie, Zhen
2024-03-11 ER
[Anonymous];Amouyal, M;Bell, A C;Bleris, L;Chen, Z Y;Chung, J H;Davidsohn, N;Guye, P;Lienert, F;Lou, C B;Lunyak, V V;Miest, T S;Qi, L;Raab, J R;Recillas-Targa, F;Szymczak, A L;Uchida, N;Wieland, M;Xie Z.;Xie, Z;Yang, J P;Yuan, Y;Yusufzai, T M
FX3ZX
Beijing, Peoples R China
5
null
3
null
29,193,957
Chang, Chih-Chun;Chen, Bor-Sen;Liao, Weixi;Lin, Ling-Jun;Ling, Che;Liu, Bing;Xie, Zhen
ACS SYNTH BIOL
Beijing, Peoples R China;Hsinchu, Taiwan
Del Vecchio, D;Qian, Y L
10.1098/rsif.2017.0902
20170902
6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
5u5z5p4k1n2a3vh3w6g3w4y5c1p5n2v2m5rt55
Realizing 'integral control' in living cells: how to overcome leaky integration due to dilution?
MIT
null
Del Vecchio, D (corresponding author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
null
Del Vecchio, Domitilla;Qian, Yili
Multidisciplinary Sciences
AFOSR [FA9550-140-1-0060]
WOS
Del Vecchio, D
MIT, Cambridge, MA USA
15
'integral;:;?;Cells;control';dilution;due;how;in;integration;leaky;living;overcome;realizing;to
1
/0000-0002-1097-0401;Del Vecchio, Domitilla
ROYAL SOC
MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA
Article
MIT
LONDON
null
null
Dept Mech Engn;MIT
AFOSR
Del Vecchio, D (corresponding author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
null
Del Vecchio, Domitilla;Qian, Yili
4
2
426,464,000,013
AFOSR [FA9550-140-1-0060]
USA
JOURNAL OF THE ROYAL SOCIETY INTERFACE
USA
null
null
MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
1742-5689
Del Vecchio, D;Qian, Y L
FEB
ddv@mit.edu
'integral control';dilution;leaky integration;living cells
2
J
Science & Technology - Other Topics
'integral control';'leaky' memory;'memory' element;ability;accumulation (integral);adaptation;adaptation error;adaptation property;biomolecular;biomolecules;cells;cellular resources;concrete guidance;consequence;CONSTRAINTS;CONTEXT;DESIGN;design principle;designing integral controllers;desired set-point;dilution;disturbances;error;fades;finding approaches;fluctuations;gene expression;GENE-EXPRESSION;general principle;Genetic circuits;growth;homeostasis;integral control;integral controller;integral controllers;integration leakiness;key aspect;leaky integration;living cells;lost;major problem;memory element;negligible;output;perturbations;process;reaching adaptation;reactions;recent years;results;RNA;ROBUST PERFECT ADAPTATION;ROBUSTNESS;significant efforts;synthetic biology;synthetic genetic circuits;time-scale separation;two synthetic genetic circuits;uncertainty;unique ability
Qian, Y L
adaptation;CONSTRAINTS;CONTEXT;DESIGN;GENE-EXPRESSION;GROWTH;HOMEOSTASIS;integral control;RNA;ROBUST PERFECT ADAPTATION;ROBUSTNESS;Synthetic biology;time-scale separation
null
[Qian, Yili; Del Vecchio, Domitilla] MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Del Vecchio, Domitilla] MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA.
This work is supported by AFOSR grant no. FA9550-140-1-0060.
'leaky' memory;'memory' element;ability;accumulation (integral);adaptation error;adaptation property;biomolecular;biomolecules;cells;cellular resources;concrete guidance;consequence;design principle;designing integral controllers;desired set-point;dilution;disturbances;error;fades;finding approaches;fluctuations;gene expression;general principle;genetic circuits;integral control;integral controller;integral controllers;integration leakiness;key aspect;living cells;lost;major problem;memory element;negligible;output;perturbations;process;reaching adaptation;reactions;recent years;results;robustness;significant efforts;synthetic genetic circuits;two synthetic genetic circuits;uncertainty;unique ability
10.1002/biot.201200085;10.1016/0005-1098(76)90006-6;10.1016/0006-3002(52)90227-8;10.1016/j.bpj.2012.12.015;10.1016/j.bpj.2015.06.034;10.1016/j.cell.2009.04.047;10.1016/j.cell.2009.12.001;10.1016/j.cels.2017.06.001;10.1016/j.ifacol.2017.08.2466;10.1016/j.jtbi.2010.07.034;10.1016/j.jtbi.2016.06.036;10.1016/S0022-2836(02)00994-4;10.1016/S0167-6911(03)00136-1;10.1021/acssynbio.6b00014;10.1021/acssynbio.6b00361;10.1021/acssynbio.7b00119;10.1021/jp3004568;10.1038/msb.2008.58;10.1038/msb4100181;10.1038/nature11478;10.1038/nbt.2461;10.1038/nprot.2013.105;10.1038/nrm2698;10.1038/nrmicro2930;10.1049/sb:20045016;10.1073/pnas.97.9.4649;10.1093/nar/gks439;10.1098/rsif.2015.1062;10.1098/rsif.2016.0380;10.1101/222042;10.1101/gad.1127103;10.1109/CDC.2010.5717525;10.1109/CDC.2014.7039358;10.1371/journal.pbio.0050229;10.23943/PRINCETON/9780691161532.001.0001;[10.1016/j.cels.2016.01.004, 10.1016/j.cels.2016.02.010]
MIT
Del Vecchio, D;Qian, Y L
Qian, Y L: MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
Qian, Yili
FA9550-140-1-0060
41
null
USA
MIT
Qian, Yili
Green Submitted, Bronze, Green Published
CONSTRAINTS;CONTEXT;DESIGN;GENE-EXPRESSION;GROWTH;HOMEOSTASIS;RNA;ROBUST PERFECT ADAPTATION;SYNTHETIC BIOLOGY
Qian, Yili; Del Vecchio, Domitilla;
null
MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA
MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, 500 Technol Sq, Cambridge, MA 02139 USA
1742-5662
adaptation;integral control;robustness;Synthetic biology;time-scale separation
139
1952;1976;1995;2000;2002;2003;2004;2006;2007;2008;2009;2010;2012;2013;2014;2015;2016;2017
65
MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
J. R. Soc. Interface
Del Vecchio, Domitilla
ROYAL SOC
'leaky';'memory';(integral);,;a;ability;accumulation;adapt;adaptation;aimed;all;an;and;any;approaches;appropriate;are;as;aspect;at;away;because;becomes;been;between;biomolecular;biomolecules;by;cells;cellular;challenged;challenging;circuits;concrete;consequence;control;controller;controllers;design;designing;desired;dilute;dilution;disturbances;due;efforts;element;error;exemplify;expression;fact;fades;faster;finding;fluctuations;for;fundamentally;gene;general;genetic;gradually;grow;guidance;have;here;however;if;implement;implementing;in;integral;integration;is;its;key;leakiness;living;lost;major;make;mathematically;memory;most;much;negligible;of;on;our;output;particular;perfectly;performance;perturbations;practically;principle;problem;process;processes;property;propose;prove;provide;reaching;reactions;realize;recent;resources;resulting;results;robustness;set-point;significant;stores;such;synthetic;than;that;the;then;there;this;to;two;unaffected;uncertainty;unique;we;with;years
MIT
A major problem in the design of synthetic genetic circuits is robustness to perturbations and uncertainty. Because of this, there have been significant efforts in recent years in finding approaches to implement integral control in genetic circuits. Integral controllers have the unique ability to make the output of a process adapt perfectly to disturbances. However, implementing an integral controller is challenging in living cells. This is because a key aspect of any integral controller is a 'memory' element that stores the accumulation (integral) of the error between the output and its desired set-point. The ability to realize such a memory element in living cells is fundamentally challenged by the fact that all biomolecules dilute as cells grow, resulting in a 'leaky' memory that gradually fades away. As a consequence, the adaptation property is lost. Here, we propose a general principle for designing integral controllers such that the performance is practically unaffected by dilution. In particular, we mathematically prove that if the reactions implementing the integral controller are all much faster than dilution, then the adaptation error due to integration leakiness becomes negligible. We exemplify this design principle with two synthetic genetic circuits aimed at reaching adaptation of gene expression to fluctuations in cellular resources. Our results provide concrete guidance on the biomolecular processes that are most appropriate for implementing integral controllers in living cells.
L-5558-2019
CONSTRAINTS;CONTEXT;DESIGN;GENE-EXPRESSION;GROWTH;HOMEOSTASIS;RNA;ROBUST PERFECT ADAPTATION;SYNTHETIC BIOLOGY
0
null
adaptation;integral control;robustness;Synthetic biology;time-scale separation
8
adaptation;CONSTRAINTS;CONTEXT;DESIGN;GENE-EXPRESSION;GROWTH;HOMEOSTASIS;integral control;RNA;ROBUST;ROBUST PERFECT ADAPTATION;Synthetic biology;time-scale separation
WOS:000426464000013
MIT, Cambridge, MA USA
USA
2,018
null
0000-0001-6472-8576;0000-0002-1097-0401
null
null
English
null
ACS SYNTH BIOL;AUTOMATICA;BIOCHIM BIOPHYS ACTA;BIOPHYS J;BioRxiv;BIOTECHNOL J;CELL;CELL SYST;FEMS MICROBIOL REV;GENE DEV;IEEE DECIS CONTR P;IFAC PAPERSONLINE;INTRO SYSTEMS BIOL D;J MOL BIOL;J PHYS CHEM B;J R SOC INTERFACE;J THEOR BIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT PROTOC;NAT REV MICROBIOL;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS BIOL;SINGULAR PERTURBATIO;SYST CONTROL LETT;SYSTEMS BIOL
Del Vecchio, Domitilla;Qian, Yili
2024-03-11 ER
Alon U.;Ang, J;Astrom K. J.;Briat, C;Cardinale, S;Del Vecchio D.;Del Vecchio, D;Drengstig, T;Francis, B A;Giladi, H;Gyorgy, A;Hussein, R;Klavins, E;Klumpp, S;Kokotovic P. K.;Levine, E;Lu, T;Mackie, G A;Massé, E;Mehta, P;Monod, J;Muzzey, D;Na, D;Olsman Noah.;Peralta-Yahya, P P;Purnick, P E M;Qian, Y L;Raveh, A;Ren, X;Rivera-Ortiz, P;Rosenfeld, N;Samaniego, C C;Shimoni, Y;Shopera, T;Sontag, E D;Tang, Z F;Yeung, E;Yi, T M;Yoo, S M
FX9XJ
Cambridge, MA USA
71
null
1
null
29,436,515
Del Vecchio, Domitilla;Qian, Yili
J R SOC INTERFACE
Cambridge, MA USA
Bleris, L;Ehrhardt, K;Kannan, S;Lee, J;Li, Y;Ma, L;Quarton, T
10.1038/s41540-017-0043-y
6
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
526f342t1li3t423h1v5x5v2d22331p2jwg6s
Mapping the operational landscape of microRNAs in synthetic gene circuits
Univ Texas Dallas
null
Bleris, L (corresponding author), Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA.;Bleris, L (corresponding author), Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA.;Bleris, L (corresponding author), Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA.
null
Bleris, Leonidas;Ehrhardt, Kristina;Kannan, Srijaa;Lee, James;Li, Yi;Ma, Lan;Quarton, Tyler
Mathematical & Computational Biology
US National Science Foundation (NSF) CAREER grant [1351354]; NSF [1361355]; University of Texas at Dallas; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [1361355] Funding Source: National Science Foundation; Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [1351354] Funding Source: National Science Foundation
WOS
Bleris, L
Univ Texas Dallas, Richardson, TX USA
4
circuits;gene;in;landscape;Mapping;microRNAs;of;operational;synthetic;the
1
Li, Yi;Quarton, Tyler
NATURE PUBLISHING GROUP
Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA;Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA.; Bleris, L (corresponding author), Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA.; Bleris, L (corresponding author), Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA;Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA;Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA;Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA
Article
Univ Texas Dallas
LONDON
null
null
Univ Texas Dallas
Direct For Mathematical & Physical Scien;Directorate For Engineering;Div Of Chem, Bioeng, Env, & Transp Sys;Division Of Mathematical Sciences;NSF;University of Texas at Dallas;US National Science Foundation (NSF) CAREER grant
Bleris, L (corresponding author), Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA.; Bleris, L (corresponding author), Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA.; Bleris, L (corresponding author), Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA.
null
Bleris, Leonidas;Ehrhardt, Kristina;Kannan, Srijaa;Lee, James;Li, Yi;Ma, Lan;Quarton, Tyler
8
4
459,652,500,002
Direct For Mathematical & Physical Scien;Directorate For Engineering [1351354] Funding Source: National Science Foundation;Div Of Chem, Bioeng, Env, & Transp Sys;Division Of Mathematical Sciences [1361355] Funding Source: National Science Foundation;NSF [1361355];University of Texas at Dallas;US National Science Foundation (NSF) CAREER grant [1351354]
USA
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
USA;USA.;
null
null
Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA
null
Bleris, L;Ehrhardt, K;Kannan, S;Lee, J;Li, Y;Ma, L;Quarton, T
JAN 11
bleris@utdallas.edu
microRNAs;operational landscape;synthetic gene circuits
7
J
Mathematical & Computational Biology
abundances;BIOLOGY;characterization;class;combination;complete operational landscape;development;disease;endogenous information;endogenous microRNAs;endogenous milieu;engineering;expression;extensive trial-and-error;function;gene expression;homeostasis;human embryonic kidney cells;input genetic template abundance;insight;interface;mathematical models;mediators;microRNA concentration;microRNA control;microRNA function;microRNA targets;MICRORNAS;miRNAs;multi-component genetic circuits;NETWORK;new insights;noncoding RNAs;observed nonlinearities;OPERATION;operational landscape;output;perfect complementarity;phenomenological;points;PROTEIN-SYNTHESIS;quantitative analysis;regulators;regulatory modules;relationship;RNA;ROBUSTNESS;ROLES;sensor systems;sequence;short;single-cell level;stepwise development;synthetic biology;synthetic biology experimentation;Synthetic gene circuit;synthetic gene circuits;ubiquitous modulators
Quarton, T
BIOLOGY;EXPRESSION;MIRNAS;NETWORK;PROTEIN-SYNTHESIS;RNA;ROBUSTNESS;SEQUENCE
null
[Quarton, Tyler; Ehrhardt, Kristina; Li, Yi; Ma, Lan; Bleris, Leonidas] Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA. [Quarton, Tyler; Ehrhardt, Kristina; Li, Yi; Bleris, Leonidas] Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA. [Lee, James; Bleris, Leonidas] Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA. [Kannan, Srijaa] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA.
This work was funded by the US National Science Foundation (NSF) CAREER grant 1351354, NSF 1361355, and the University of Texas at Dallas.
abundances;characterization;class;combination;complete operational landscape;development;disease;endogenous information;endogenous microRNAs;endogenous milieu;engineering;extensive trial-and-error;function;gene expression;homeostasis;human embryonic kidney cells;input genetic template abundance;insight;interface;mathematical models;mediators;microRNA concentration;microRNA control;microRNA function;microRNA targets;microRNAs;multi-component genetic circuits;new insights;noncoding RNAs;observed nonlinearities;operation;output;perfect complementarity;phenomenological;points;quantitative analysis;regulators;regulatory modules;relationship;roles;sensor systems;short;single-cell level;stepwise development;synthetic biology;synthetic biology experimentation;synthetic gene circuit;synthetic gene circuits;ubiquitous modulators
10.1007/978-1-61779-412-4_10;10.1016/j.bios.2015.07.035;10.1016/j.cbpa.2012.05.192;10.1016/j.cell.2007.05.045;10.1016/j.cell.2009.01.002;10.1016/j.cell.2009.01.035;10.1016/j.cell.2009.01.058;10.1016/j.cell.2011.01.030;10.1016/j.cell.2012.04.005;10.1016/j.cels.2017.01.003;10.1016/j.molcel.2007.05.018;10.1016/j.tcb.2006.12.007;10.1021/sb4001596;10.1021/sb4001867;10.1038/35888;10.1038/msb.2008.62;10.1038/msb.2011.49;10.1038/nature02872;10.1038/nature07242;10.1038/nature09267;10.1038/nbt1307;10.1038/ncb0309-228;10.1038/ncomms2471;10.1038/ng.905;10.1038/nrg1328;10.1038/nrg3094;10.1038/nrm3611;10.1038/srep32823;10.1039/c3mb70043g;10.1073/pnas.1205693109;10.1073/pnas.1304840111;10.1073/pnas.1413896112;10.1126/science.1190544;10.1126/science.1205527;10.1126/science.1206843;10.1126/science.aaa1738;10.1371/journal.pcbi.1001101;10.1371/journal.pcbi.1004653;10.15252/msb.20167265;10.2307/2965437;[10.1038/nnano.2010.135, 10.1038/NNANO.2010.135]
Univ Texas Dallas
Bleris, L;Ehrhardt, K;Kannan, S;Lee, J;Li, Y;Ma, L;Quarton, T
Quarton, T: Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA
Bleris, Leonidas
1351354;1361355
42
null
USA
Univ Texas Dallas
Quarton, Tyler
gold, Green Published
BIOLOGY;EXPRESSION;MIRNAS;NETWORK;PROTEIN-SYNTHESIS;RNA;ROBUSTNESS;SEQUENCE
Quarton, Tyler; Ehrhardt, Kristina; Lee, James; Kannan, Srijaa; Li, Yi; Ma, Lan; Bleris, Leonidas;
null
Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA;Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA;Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA;Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA
Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA;Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA;Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA;Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA
2056-7189
null
null
1995;1998;2004;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
12
Univ Texas Dallas, Bioengn Dept, Richardson, TX 75083 USA;Univ Texas Dallas, Ctr Syst Biol, Richardson, TX 75083 USA;Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75083 USA
npj Syst. Biol. Appl.
Bleris, Leonidas
NATURE PUBLISHING GROUP
,;a;abundance;abundances;an;analysis;and;are;as;at;between;biology;cells;characterization;circuit;circuits;class;combination;complementarity;complete;concentration;contains;control;derive;development;disease;embryonic;employs;enables;endogenous;engineered;engineering;equipped;establish;experimentally;experimentation;expression;extensive;facilitates;features;framework;frequently;function;gene;genetic;here;homeostasis;human;in;information;input;insight;insights;interface;into;investigate;is;kidney;landscape;level;mathematical;mediators;microRNA;microRNAs;milieu;model;models;modulators;modules;moreover;multi-component;new;noncoding;nonlinearities;now;observed;of;on;operation;operational;optimized;our;output;perfect;phenomenological;points;provide;quantitative;recapitulates;regulators;regulatory;relationship;RNAs;roles;sensor;short;single-cell;specifically;stepwise;synthetic;systems;targets;template;that;the;through;to;trial-and-error;typically;ubiquitous;under;used;using;various;we;with;work
Univ Texas Dallas
MicroRNAs are a class of short, noncoding RNAs that are ubiquitous modulators of gene expression, with roles in development, homeostasis, and disease. Engineered microRNAs are now frequently used as regulatory modules in synthetic biology. Moreover, synthetic gene circuits equipped with engineered microRNA targets with perfect complementarity to endogenous microRNAs establish an interface with the endogenous milieu at the single-cell level. The function of engineered microRNAs and sensor systems is typically optimized through extensive trial-and-error. Here, using a combination of synthetic biology experimentation in human embryonic kidney cells and quantitative analysis, we investigate the relationship between input genetic template abundance, microRNA concentration, and output under microRNA control. We provide a framework that employs the complete operational landscape of a synthetic gene circuit and enables the stepwise development of mathematical models. We derive a phenomenological model that recapitulates experimentally observed nonlinearities and contains features that provide insight into the microRNA function at various abundances. Our work facilitates the characterization and engineering of multi-component genetic circuits and specifically points to new insights on the operation of microRNAs as mediators of endogenous information and regulators of gene expression in synthetic biology.
A-6761-2009
BIOLOGY;EXPRESSION;MIRNA;NETWORKS;PROTEIN-SYNTHESIS;RNA;ROBUST;SEQUENCE
0
null
null
7
BIOLOGY;EXPRESSION;miRNA;NETWORKS;PROTEIN-SYNTHESIS;RNA;ROBUST;SEQUENCE
WOS:000459652500002
Univ Texas Dallas, Richardson, TX USA
USA
2,018
null
0000-0001-6389-7888;0000-0003-2086-3519
null
null
English
null
ACS SYNTH BIOL;BIOSENS BIOELECTRON;CELL;CELL SYST;CURR OPIN CHEM BIOL;J Biol Eng;METHODS MOL BIOL;MOL BIOSYST;MOL CELL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CELL BIOL;NAT COMMUN;NAT GENET;NAT NANOTECHNOL;NAT REV GENET;NAT REV MOL CELL BIO;NATURE;P NATL ACAD SCI USA;PLOS COMPUT BIOL;SCI REP-UK;SCIENCE;TRENDS CELL BIOL
Bleris, Leonidas;Ehrhardt, Kristina;Kannan, Srijaa;Lee, James;Li, Yi;Ma, Lan;Quarton, Tyler
2024-03-11 ER
Acar, M;Ameres, S L;Baek, D;Balázsi, G;Bartel, D P;Beisel, C L;Benenson, Y;Bishop C.M.;Bleris, L;Bloom R., J;Carthew, R W;Deans, T L;Del Rosario, R C H;Ebert, M S;Egbert, R G;Ehrhardt, K;Fire, A;Guinn, M;Guo, H L;Kashyap, N;Lee, J;Leisner, M;Li, X;Mello, C C;Mohammadi, P;Moore, R;Mukherji, S;Nevozhay, D;Osella, M;Pillai, R S;Rinaudo, K;Ruder, W C;Schmiedel, J M;Schreiber, J;Strovas, T J;Tsang, J;Weber, W;Winter, J;Xie, Z;Yuan, Y
HM7IT
Richardson, TX USA;Richardson, TX USA.
14
null
1
null
29,354,284
Bleris, Leonidas;Ehrhardt, Kristina;Kannan, Srijaa;Lee, James;Li, Yi;Ma, Lan;Quarton, Tyler
NPJ SYST BIOL APPL
Richardson, TX USA
Bashor, C J;Collins, J J
10.1146/annurev-biophys-070816-033903
null
4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
1a271g2p3k256v392c5d6t1l4oy1d1k314f3p13
Understanding Biological Regulation Through Synthetic Biology
MIT
Annual Review of Biophysics
Bashor, CJ (corresponding author), MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA.;Bashor, CJ (corresponding author), MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA.
null
Bashor, Caleb J;Collins, James J
Biophysics
null
WOS
Bashor, C J
Broad Inst MIT & Harvard, Cambridge, MA USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Boston, MA USA;MIT, Cambridge, MA USA
47
biological;biology;regulation;synthetic;through;understanding
1
null
ANNUAL REVIEWS
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA;Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA;MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA.; Bashor, CJ (corresponding author), MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA
Review; Book Chapter
MIT
PALO ALTO
null
null
Broad Inst MIT & Harvard;Harvard MIT Program Hlth Sci & Technol;Harvard Univ;Inst Med Engn & Sci;MIT
null
Bashor, CJ (corresponding author), MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA.; Bashor, CJ (corresponding author), MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA.
423
Bashor, Caleb J;Collins, James J
63
5
433,056,800,019
null
USA
ANNUAL REVIEW OF BIOPHYSICS, VOL 47
USA;USA.;
null
null
MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA
1936-122X
Bashor, C J;Collins, J J
null
cbashor@mit.edu;jimjc@mit.edu
synthetic biology;understanding Biological Regulation
2
S
Biophysics
biological discovery;building;cellular phenotype;cellular regulation;cellular regulation serves;circuit engineering;CIRCUITS;engineering cycle;engineering synthetic gene regulatory circuits;ESCHERICHIA-COLI;furnished biologists;gene circuit engineering;initial circuit designs;iterative cycles;living cells;logic gates;MAMMALIAN-CELLS;motif;natural network function;natural systems;network structure;networks;observed circuit behavior;often-incomplete models;POSITIVE-FEEDBACK;precision manipulation;predictively;process;PROTEIN MODULES;reductive inquiry-biochemistry;refactoring;regulation;REGULATORY NETWORK;rely;resynthesis;single-cell level;STOCHASTIC GENE-EXPRESSION;synthetic biology;Synthetic gene circuit;synthetic gene circuit engineering research;systems biology;systems-level network function;testing;toolkit;turn;ultimate means;understanding;understanding Biological Regulation
Bashor, C J
CIRCUITS;engineering cycle;ESCHERICHIA-COLI;LIVING CELLS;logic gates;MAMMALIAN-CELLS;motif;NETWORKS;POSITIVE-FEEDBACK;PROTEIN MODULES;refactoring;REGULATORY NETWORK;SINGLE-CELL LEVEL;STOCHASTIC GENE-EXPRESSION;Synthetic biology;Synthetic gene circuit
399
[Bashor, Caleb J.; Collins, James J.] MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA. [Bashor, Caleb J.; Collins, James J.] MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA. [Collins, James J.] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA. [Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Collins, James J.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA.
null
biological discovery;building;cellular phenotype;cellular regulation;cellular regulation serves;circuit engineering;engineering cycle;engineering synthetic gene regulatory circuits;furnished biologists;gene circuit engineering;initial circuit designs;iterative cycles;natural network function;natural systems;network structure;observed circuit behavior;often-incomplete models;precision manipulation;predictively;process;reductive inquiry-biochemistry;regulation;rely;resynthesis;synthetic gene circuit engineering research;systems biology;systems-level network function;testing;toolkit;turn;ultimate means;understanding
10.1002/biot.201000181;10.1016/j.cell.2005.06.006;10.1016/j.cell.2008.06.030;10.1016/j.cell.2009.07.046;10.1016/j.cell.2010.12.014;10.1016/j.cell.2011.01.032;10.1016/j.cell.2012.05.045;10.1016/j.cell.2012.08.040;10.1016/j.cell.2013.02.022;10.1016/j.cell.2014.04.047;10.1016/j.cell.2014.10.002;10.1016/j.cell.2014.10.004;10.1016/j.cell.2015.02.009;10.1016/j.cell.2016.02.004;10.1016/j.cell.2016.04.059;10.1016/j.cell.2016.09.013;10.1016/j.cels.2017.06.001;10.1016/j.copbio.2006.08.001;10.1016/j.copbio.2009.07.009;10.1016/j.molcel.2016.06.006;10.1016/j.sbi.2007.12.002;10.1016/j.sbi.2016.06.012;10.1016/j.tibtech.2015.12.014;10.1016/S0006-3495(00)76519-2;10.1016/S0022-2836(61)80072-7;10.1016/S0092-8674(00)80566-8;10.1038/35002125;10.1038/35002131;10.1038/35011540;10.1038/35014651;10.1038/373573a0;10.1038/468889a;10.1038/nature01546;10.1038/nature02870;10.1038/nature04342;10.1038/nature04473;10.1038/nature04588;10.1038/nature05851;10.1038/nature06847;10.1038/nature07389;10.1038/nature08753;10.1038/nature09906;10.1038/nature13238;10.1038/nature19841;10.1038/nature20777;10.1038/nbt.2510;10.1038/nbt.3053;10.1038/nbt.3063;10.1038/nbt.3199;10.1038/nbt.3805;10.1038/nbt986;10.1038/nchembio.1411;10.1038/ng869;10.1038/nrg2499;10.1038/nrg2775;10.1038/nrm2203;10.1038/nrm2698;10.1038/nrm2746;10.1038/nrmicro3239;10.1038/scientificamerican1182-128;10.1039/c0ib00070a;10.1073/pnas.1009747107;10.1073/pnas.1202344109;10.1073/pnas.1332628100;10.1073/pnas.1508521112;10.1073/pnas.1610973113;10.1073/pnas.1934711100;10.1073/pnas.94.3.814;10.1073/pnas.95.15.8420;10.1088/1468-6996/15/1/014401;10.1093/emboj/20.10.2528;10.1093/nar/25.6.1203;10.1098/rsif.2016.0380;10.1101/cshperspect.a023978;10.1101/sqb.2015.80.027557;10.1103/PhysRevLett.88.148101;10.1113/jphysiol.1952.sp004764;10.1126/science.1063127;10.1126/science.1070919;10.1126/science.1076979;10.1126/science.1085945;10.1126/science.1089072;10.1126/science.1106914;10.1126/science.1109090;10.1126/science.1137455;10.1126/science.1151153;10.1126/science.1172005;10.1126/science.1205527;10.1126/science.1206843;10.1126/science.1232758;10.1126/science.1255301;10.1126/science.1256272;10.1126/science.131.3412.1503;10.1126/science.298.5594.824;10.1126/science.aaa3794;10.1126/science.aab2956;10.1126/science.aac7341;10.1126/science.aad8559;10.1126/scitranslmed.3005568;10.1146/annurev.bioeng.5.040202.121553;10.1146/annurev.biophys.050708.133652;10.1529/biophysj.107.118687;[10.1038/NMETH.2969, 10.1038/nmeth.2969];[10.1038/NMETH.3312, 10.1038/nmeth.3312];[10.1038/NMETH.3339, 10.1038/nmeth.3339];[10.1038/NMETH.3585, 10.1038/nmeth.3585];[10.1038/nprot.2013.021, 10.1038/nprot.nprot.2013.021]
MIT
Bashor, C J;Collins, J J
Bashor, C J: MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA
null
null
108
978-0-8243-1847-5
USA
Broad Inst MIT & Harvard;Harvard MIT Program Hlth Sci & Technol;Harvard Univ;MIT
Bashor, Caleb J
Bronze, Green Published
CIRCUITS;ESCHERICHIA-COLI;LIVING CELLS;LOGIC GATES;MAMMALIAN-CELLS;NETWORKS;POSITIVE-FEEDBACK;PROTEIN MODULES;SINGLE-CELL LEVEL;STOCHASTIC GENE-EXPRESSION
Bashor, Caleb J.; Collins, James J.;
null
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA;Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA;MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA;Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA;MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA
null
engineering cycle;motif;refactoring;regulatory network;Synthetic biology;Synthetic gene circuit
null
1952;1960;1961;1982;1995;1997;1998;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
65
MIT, Inst Med Engn & Sci, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA
Annu. Rev. Biophys.
Collins, James J
ANNUAL REVIEWS
,;a;advance;and;are;as;at;be;behavior;biological;biologists;biology;building;but;by;can;cellular;circuit;circuits;cycle;cycles;design;designed;designs;differences;directed;discovery;discuss;each;emerges;encountered;engineering;established;exact;experimentally;fields;force;from;function;furnished;gene;has;here;how;in;inevitably;initial;inquiry-biochemistry;investigated;iterative;manipulation;means;models;molecular;must;natural;network;not;observed;of;often-incomplete;on;only;our;outline;phenotype;precision;predictively;proceeds;process;reconstruct;reductive;refined;regulation;regulatory;rely;reorganize;research;resolved;resynthesis;rewire;serves;structure;synthetic;systems;systems-level;testing;that;the;through;to;toolkit;turn;ultimate;understanding;uses;using;we;with
MIT
Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.
null
CIRCUITS;ESCHERICHIA-COLI;LIVING CELLS;LOGIC GATES;MAMMALIAN-CELLS;NETWORKS;POSITIVE FEEDBACK;PROTEIN MODULES;SINGLE-CELL LEVEL;STOCHASTIC GENE-EXPRESSION
2
null
engineering cycle;motif;refactoring;regulatory network;Synthetic biology;Synthetic gene circuit
25
ESCHERICHIA-COLI;CIRCUITS;engineering cycle;LIVING CELLS;logic gates;MAMMALIAN-CELLS;MOTIFS;NETWORKS;Positive feedback;PROTEIN MODULES;refactoring;REGULATORY NETWORKS;SINGLE-CELL LEVEL;STOCHASTIC GENE-EXPRESSION;Synthetic biology;synthetic gene circuits
WOS:000433056800019
Broad Inst MIT & Harvard, Cambridge, MA USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Boston, MA USA;MIT, Cambridge, MA USA
USA
2,018
null
null
null
Dill, KA
English
null
ANNU REV BIOMED ENG;ANNU REV BIOPHYS;BIOPHYS J;BIOTECHNOL J;CELL;CELL SYST;COLD SH Q B;CSH PERSPECT BIOL;CURR OPIN BIOTECH;CURR OPIN STRUC BIOL;EMBO J;INTEGR BIOL-UK;J MOL BIOL;J PHYSIOL-LONDON;J R SOC INTERFACE;MOL CELL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT GENET;NAT METHODS;NAT PROTOC;NAT REV GENET;NAT REV MICROBIOL;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV LETT;SCI AM;SCI TECHNOL ADV MAT;SCI TRANSL MED;SCIENCE;TRENDS BIOTECHNOL
Bashor, Caleb J;Collins, James J
2024-03-11 ER
Alon, U;Appleton, E;Barrett, C L;Bashor, C J;Becskei, A;Bintu, L;Blake, W J;Bonnet, J;Brophy, J A N;Callura, J M;Cameron, D E;Carroll, S B;Ceroni, F;Chau, A H;Chavez, A;Chen, Y;Danino, T;Del Vecchio, D;Detwiler, P B;Dueber, J E;Dunlap, J C;Ellis, T;Elowitz, M;Elowitz, M B;Endy, D;Ernst, J;Erwin, D H;Farzadfard, F;Fischbach, M;Fischbach, M A;Frieda, K L;Friedland, A E;Gardner, T S;Gordley, R M;Green, A A;Guido, N J;Hannon, G J;Hartwell, L H;Hasty, J;Hilton, I B;Hodgkin, A L;Howard, P L;Isaacs, F J;Isalan, M;Jacob, F;Jenuwein, T;Jones, D L;Jusiak, B;Keung, A J;Khalil, A S;Kiani, S;Kirschner, M;Kornberg, A;Kærn, M;Lee, J W;Liu, A P;Lutz, R;Mcadams, H H;Milo, R;Nielsen, A A K;Nielsen, J;Nocedal, I;O'Shaughnessy, E C;Ozbudak, E M;Panne, D;Pardee, K;Park, S H;Pawson, T;Pedraza, J M;Potvin-Trottier, L;Prindle, A;Ptashne, M;Purnick, P E M;Qi, L S;Razooky, B S;Rice, M K;Roquet, N;Rosenfeld, N;Ruder, W C;Siuti, P;Slomovic, S;Smanski, M J;Stanton, B C;Stricker, J;Süel, G M;Tigges, M;Toprak, E;Ubersax, J A;Weinberg, B H;Weinberger, L S;Xie, Z;Yeh, B J;Yeung, E;Young, R A
BK2KQ
Cambridge, MA USA;Cambridge, MA USA.
78
null
4
null
29,547,341
Bashor, Caleb J;Collins, James J
ANNU REV BIOPHYS
Boston, MA USA;Cambridge, MA USA
Ellis, T;Pothoulakis, G
10.1038/s42003-017-0008-0
7
75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
m6n5s2e2o4x6x4i414o136c7133712v2t6o6k3z
Synthetic gene regulation for independent external induction of the <i>Saccharomyces cerevisiae</i> pseudohyphal growth phenotype
Imperial Coll London
null
Ellis, T (corresponding author), Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England.;Ellis, T (corresponding author), Imperial Coll London, Dept Bioengn, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England.
null
Ellis, Tom;Pothoulakis, Georgios
Biology;Multidisciplinary Sciences
Leverhulme Trust [RPG-2012-562]; BBSRC [BB/K006290/1]; BBSRC [BB/K006290/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/K006290/1] Funding Source: researchfish
WOS
Ellis, T
Imperial Coll London, London, England
1
<i>Saccharomyces;cerevisiae</i>;external;for;gene;growth;Independent;induction;of;phenotype;pseudohyphal;regulation;synthetic;the
1
Pothoulakis, Georgios
NATURE PUBLISHING GROUP
Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England;Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England.; Ellis, T (corresponding author), Imperial Coll London, Dept Bioengn, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England;Imperial Coll London, Dept Bioengn, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England
Article
Imperial Coll London
NEW YORK
null
null
Imperial Coll London
BBSRC;Biotechnology and Biological Sciences Research Council;Leverhulme Trust
Ellis, T (corresponding author), Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England.; Ellis, T (corresponding author), Imperial Coll London, Dept Bioengn, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England.
null
Ellis, Tom;Pothoulakis, Georgios
4
2
461,126,500,007
BBSRC [BB/K006290/1];BBSRC [BB/K006290/1] Funding Source: UKRI;Biotechnology and Biological Sciences Research Council [BB/K006290/1] Funding Source: researchfish;Leverhulme Trust [RPG-2012-562]
UK
COMMUNICATIONS BIOLOGY
UK
null
null
Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England
null
Ellis, T;Pothoulakis, G
null
t.ellis@imperial.ac.uk
<i>Saccharomyces cerevisiae</i> pseudohyphal growth phenotype;independent external induction;Synthetic Gene Regulation
2
J
Life Sciences & Biomedicine - Other Topics;Science & Technology - Other Topics
<i>Saccharomyces cerevisiae</i> pseudohyphal growth phenotype;branched filament structures;BUD gene family control filamentation;BUD-SITE-SELECTION;complex multigene phenotype;connected cells;CONSTRUCTION;control;different types;differentiation;diploid;expression;external induction;FILAMENTOUS GROWTH;FLO8 genes;gene regulation;gross changes;haploid cells;HAPLOID INVASIVE GROWTH;haploid yeast;independent external induction;members;multicellular phenotype;natural PHD1;networks;offers opportunities;pattern;PROTEIN;pseudohyphal growth;response;resulting multicellular structure;reversibility;rich media;Saccharomyces cerevisiae;Stress;Synthetic Gene Regulation;synthetic gene regulation systems;synthetic genetic timer network;synthetic regulation;SYSTEM;TRANSCRIPTION;unicellular yeast cells;wild budding yeast cells;yeast
Pothoulakis, G
BUD-SITE-SELECTION;CONSTRUCTION;EXPRESSION;FILAMENTOUS GROWTH;HAPLOID INVASIVE GROWTH;NETWORKS;PATTERN;PROTEIN;TRANSCRIPTION;YEAST
null
[Pothoulakis, Georgios; Ellis, Tom] Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England. [Pothoulakis, Georgios; Ellis, Tom] Imperial Coll London, Dept Bioengn, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England.
The authors wish to thank William Shaw (Imperial College London) for his assistance on the implementation of the Yeast ToolKit and providing certain YTK part plasmids. We also thank Marios Tomazou, Felix Jonas and all other helpful members of CSynBI at Imperial College London. This work was funded by The Leverhulme Trust under project grant RPG-2012-562 and by the BBSRC via grant BB/K006290/1.
branched filament structures;BUD gene family control filamentation;complex multigene phenotype;connected cells;control;different types;differentiation;diploid;expression;external induction;FLO8 genes;gene regulation;gross changes;haploid cells;haploid yeast;members;multicellular phenotype;natural PHD1;offers opportunities;pseudohyphal growth;response;resulting multicellular structure;reversibility;rich media;Saccharomyces cerevisiae;stress;synthetic gene regulation systems;synthetic genetic timer network;synthetic regulation;system;unicellular yeast cells;wild budding yeast cells
10.1002/j.1460-2075.1991.tb04901.x;10.1007/s004380050220;10.1016/j.febslet.2012.01.053;10.1016/j.ymeth.2012.08.004;10.1016/S0168-6445(00)00056-5;10.1016/S1369-5274(02)00300-4;10.1021/sb500366v;10.1038/274765a0;10.1038/nbt.1536;10.1038/nbt1162;10.1038/nrmicro1578;10.1046/j.1365-2958.2003.03478.x;10.1073/pnas.0407097102;10.1073/pnas.0608451104;10.1073/pnas.1305423110;10.1073/pnas.1522679113;10.1073/pnas.240345197;10.1083/jcb.134.2.413;10.1091/mbc.11.3.833;10.1091/mbc.12.7.2147;10.1091/mbc.12.8.2497;10.1091/mbc.5.9.1003;10.1091/mbc.E02-03-0151;10.1093/nar/gks1313;10.1093/nar/gkt1402;10.1101/PDB.T0P065482;10.1111/j.1574-6976.2011.00275.x;10.1111/jam.13078;10.1126/science.1224339;10.1128/AEM.00425-07;10.1128/EC.00284-06;10.1128/EC.4.6.1018-1028.2005;10.1128/EC.4.8.1328-1342.2005;10.1128/MCB.05420-11;10.1128/MCB.10.9.4757;10.1128/MCB.14.3.2100;10.1128/MCB.8.10.4048;10.1128/MMBR.00037-06;10.1128/MMBR.69.2.326-356.2005;10.1242/dev.00425;10.1371/journal.pgen.1005684;10.1534/genetics.111.127456
Imperial Coll London
Ellis, T;Pothoulakis, G
Pothoulakis, G: Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England
Pothoulakis, Georgios
BB/K006290/1;RPG-2012-562
45
null
UK
Imperial Coll London
Pothoulakis, Georgios
Green Published, gold
BUD-SITE-SELECTION;CONSTRUCTION;EXPRESSION;FILAMENTOUS GROWTH;HAPLOID INVASIVE GROWTH;NETWORKS;PATTERN;PROTEIN;TRANSCRIPTION;YEAST
Pothoulakis, Georgios; Ellis, Tom;
null
Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England;Imperial Coll London, Dept Bioengn, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England
Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England;Imperial Coll London, Dept Bioengn, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England
2399-3642
null
null
1978;1988;1990;1991;1994;1996;1997;2000;2001;2002;2003;2005;2007;2009;2011;2012;2013;2014;2015;2016
14
Imperial Coll London, Ctr Synthet Biol & Innovat, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England;Imperial Coll London, Dept Bioengn, South Kensington Campus,Exhibit Rd, London SW7 2AZ, England
Commun. Biol.
Ellis, Tom
NATURE PUBLISHING GROUP
,;a;able;also;and;are;both;branched;BUD;budding;by;can;cells;cerevisiae;changes;complex;connected;consisting;construct;control;controlling;demonstrates;different;differentiation;diploid;elongate;employ;enable;even;exert;explore;expression;external;family;filament;filamentation;finally;FLO8;for;form;further;gene;genes;genetic;gross;growth;haploid;here;how;in;induction;investigate;is;media;members;modifying;multicellular;multigene;natural;naturally;network;of;offers;opportunities;our;over;performed;PHD1;phenotype;pseudohyphal;rationally;regulation;response;resulting;reversibility;rich;Saccharomyces;stress;structure;structures;synthetic;system;systems;that;the;their;this;timer;to;trigger;types;undergo;unicellular;using;we;wild;work;yeast
Imperial Coll London
Pseudohyphal growth is a multicellular phenotype naturally performed by wild budding yeast cells in response to stress. Unicellular yeast cells undergo gross changes in their gene regulation and elongate to form branched filament structures consisting of connected cells. Here, we construct synthetic gene regulation systems to enable external induction of pseudohyphal growth in Saccharomyces cerevisiae. By controlling the expression of the natural PHD1 and FLO8 genes we are able to trigger pseudohyphal growth in both diploid and haploid yeast, even in different types of rich media. Using this system, we also investigate how members of the BUD gene family control filamentation in haploid cells. Finally, we employ a synthetic genetic timer network to control pseudohyphal growth and further explore the reversibility of differentiation. Our work demonstrates that synthetic regulation can exert control over a complex multigene phenotype and offers opportunities for rationally modifying the resulting multicellular structure.
HLQ-6280-2023
BUD-SITE-SELECTION;CONSTRUCTION;EXPRESSION;FILAMENTOUS GROWTH;HAPLOID INVASIVE GROWTH;NETWORKS;PATTERNS;PROTEIN;TRANSCRIPTION;YEAST
0
null
null
11
YEAST;BUD-SITE-SELECTION;CONSTRUCTION;EXPRESSION;FILAMENTOUS GROWTH;HAPLOID INVASIVE GROWTH;NETWORKS;PATTERNS;PROTEIN;TRANSCRIPTION
WOS:000461126500007
Imperial Coll London, London, England
UK
2,018
null
0000-0003-2950-3990
null
null
English
null
ACS SYNTH BIOL;APPL ENVIRON MICROB;Cold Spring Harb Protoc;CURR OPIN MICROBIOL;DEVELOPMENT;EMBO J;EUKARYOT CELL;FEBS LETT;FEMS MICROBIOL REV;GENETICS;J APPL MICROBIOL;J CELL BIOL;METHODS;MICROBIOL MOL BIOL R;MOL BIOL CELL;MOL CELL BIOL;MOL GEN GENET;MOL MICROBIOL;NAT BIOTECHNOL;NAT REV MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS GENET;SCIENCE
Ellis, Tom;Pothoulakis, Georgios
2024-03-11 ER
Albers, E;Ashe, M P;Bahn, Y S;Basu, S;Blount, B A;Brückner, S;Casamayor, A;Chen, M T;Cullen, P J;Dang, C V;Douglas, L M;Dranginis, A M;Ellis, T;Farabaugh, P J;Flick, J S;Gancedo, J M;Gimeno, C J;Harkins, H A;Hughes, R M;Kim, J;Kobayashi, O;Kron, S J;Kumamoto, C A;Lee, M E;Liu, H P;Mcisaac, R S;Mosch, H U;Murphy, K F;Nehlin, J O;Ni, L;Park, Y N;Raithatha, S;Ramos, J L;Rines Danielr.;Ryan, O;Salazar-Ciudad, I;Sanders, S L;Sharma, G;Voth, W P;Wu, M;Yin, Z K;Zahner, J E
HO7LC
London, England;London, England.
15
null
1
null
30,271,894
Ellis, Tom;Pothoulakis, Georgios
COMMUN BIOL
London, England
Arangundy-Franklin, S;Holliger, P;Houlihan, G
10.1016/j.copbio.2017.04.004
null
THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
6v366y246u4b5p1c2dp51u2034o1t143u5s23
Engineering and application of polymerases for synthetic genetics
MRC Lab Mol Biol
null
Holliger, P (corresponding author), MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
null
Arangundy-Franklin, Sebastian;Holliger, Philipp;Houlihan, Gillian
Biochemical Research Methods;Biotechnology & Applied Microbiology
Medical Research Council [MC_U105178804]; MRC-AstraZeneca/MedImmune Blue Sky Grant; Medical Research Council [MC_U105178804] Funding Source: researchfish; MRC [MC_U105178804] Funding Source: UKRI
WOS
Holliger, P
MRC Lab Mol Biol, Cambridge, England
48
and;application;engineering;for;Genetics;of;polymerases;synthetic
1
null
ELSEVIER SCI LTD
MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
Review
MRC Lab Mol Biol
OXFORD
null
null
MRC Lab Mol Biol
Medical Research Council;MRC;MRC-AstraZeneca/MedImmune Blue Sky Grant
Holliger, P (corresponding author), MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
179
Arangundy-Franklin, Sebastian;Holliger, Philipp;Houlihan, Gillian
55
1
418,313,200,023
Medical Research Council [MC_U105178804];Medical Research Council [MC_U105178804] Funding Source: researchfish;MRC [MC_U105178804] Funding Source: UKRI;MRC-AstraZeneca/MedImmune Blue Sky Grant
UK
CURRENT OPINION IN BIOTECHNOLOGY
UK
null
null
MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
0958-1669
Arangundy-Franklin, S;Holliger, P;Houlihan, G
DEC
ph1@mrc-lmb.cam.ac.uk
application;engineering;polymerases;Synthetic Genetics
3
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
application;backbone moieties;chemical determinants;COMBINATORIAL SELECTION;concomitantly;conjunction;crosstalk;CRYSTAL-STRUCTURE;directed evolution;discovery;DNA-POLYMERASE;engineering;engineering polymerases;ENZYMATIC-SYNTHESIS;evolution;exploration;function;genetic alphabet;genetic information;given rise;IN-VITRO SELECTION;information exchange;investigation;modified nucleotide analogs;molecular biology;natural genetic system;new field;novel;novel unnatural basepairs;nucleic acids;NUCLEIC-ACIDS;nucleobase;nucleotide chemistry;organic chemistry;polymerases;progress;PROPAGATION;protein engineering;recent progress;reverse transcription;REVERSE-TRANSCRIPTASE;SEMISYNTHETIC ORGANISM;STORAGE;sugar ring;synthetic genetic polymers;synthetic genetics;synthetic nucleic acids;T7 RNA-POLYMERASE;templated synthesis;two lines;variation
Houlihan, G
COMBINATORIAL SELECTION;CRYSTAL-STRUCTURE;directed evolution;DNA-POLYMERASE;ENZYMATIC-SYNTHESIS;IN-VITRO SELECTION;NUCLEIC-ACIDS;REVERSE-TRANSCRIPTASE;SEMISYNTHETIC ORGANISM;T7 RNA-POLYMERASE
168
[Houlihan, Gillian; Arangundy-Franklin, Sebastian; Holliger, Philipp] MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
The authors acknowledge support by the Medical Research Council (G.H., P.H., program no. MC_U105178804) and an MRC-AstraZeneca/MedImmune Blue Sky Grant supporting the salary of S.A-F.
backbone moieties;chemical determinants;concomitantly;conjunction;crosstalk;discovery;engineering polymerases;evolution;exploration;function;genetic alphabet;genetic information;given rise;information exchange;investigation;modified nucleotide analogs;molecular biology;natural genetic system;new field;novel;novel unnatural basepairs;nucleic acids;nucleobase;nucleotide chemistry;organic chemistry;polymerases;progress;propagation;protein engineering;recent progress;reverse transcription;storage;sugar ring;synthetic genetic polymers;synthetic genetics;synthetic nucleic acids;templated synthesis;two lines;variation
10.1002/1439-7633(20010302)2:3<212::AID-CBIC212>3.0.CO;2-R;10.1002/anie.201503652;10.1002/anie.201508678;10.1002/anie.201606242;10.1002/cbdv.200900185;10.1002/cbic.201000384;10.1002/cbic.201600136;10.1002/j.1460-2075.1995.tb00140.x;10.1007/s00216-013-7350-y;10.1007/s00253-015-6781-0;10.1016/j.bbrc.2014.09.053;10.1016/j.bbrc.2015.03.019;10.1016/j.biomaterials.2014.08.046;10.1016/j.cbpa.2008.06.028;10.1016/j.cbpa.2016.08.001;10.1016/j.cell.2013.04.046;10.1016/j.chembiol.2004.10.017;10.1016/j.jbiotec.2013.07.005;10.1016/j.jmb.2006.06.050;10.1016/S0040-4020(98)00094-5;10.1021/acs.biochem.5b00689;10.1021/acschembio.5b00949;10.1021/acssynbio.6b00228;10.1021/ar040004z;10.1021/bi0507074;10.1021/bi1009503;10.1021/bi101915z;10.1021/bi400558c;10.1021/ja038525p;10.1021/ja0428255;10.1021/ja045364w;10.1021/ja412079b;10.1021/ja508015a;10.1021/ja9039696;10.1021/ja906186f;10.1021/jacs.5b02251;10.1021/jacs.5b03482;10.1021/jacs.6b10767;10.1038/nature12306;10.1038/nature13314;10.1038/nature13982;10.1038/nature21022;10.1038/nbt.2556;10.1038/nbt1001;10.1038/nbt974;10.1038/ncomms11235;10.1038/ncomms7923;10.1038/nrd.2016.199;10.1038/nrd1955;10.1039/c4mb00436a;10.1039/c5mb00045a;10.1042/EBC20160013;10.1073/pnas.071052198;10.1073/pnas.102577799;10.1073/pnas.1120964109;10.1073/pnas.1311778111;10.1073/pnas.132067399;10.1073/pnas.1616443114;10.1074/jbc.M112.442350;10.1074/jbc.M113.532697;10.1074/jbc.R400006200;10.1093/molbev/msu271;10.1093/nar/gkn1070;10.1093/nar/gkn956;10.1093/nar/gkv1057;10.1093/nar/gkv1472;10.1093/nar/gkv367;10.1093/nar/gkv719;10.1093/nar/gkv734;10.1093/nar/gkv798;10.1093/nar/gkx079;10.1093/nar/gnf138;10.1126/science.1217622;10.1126/science.290.5495.1347;10.1126/science.aad9633;10.1126/science.aaf5409;10.1146/annurev.biochem.66.1.337;10.1371/journal.pone.0015004;10.3389/fmicb.2014.00305;10.4161/rna.27447;[10.1038/NCHEM.1241, 10.1038/nchem.1241];[10.1038/NCHEM.2493, 10.1038/nchem.2493];[10.1038/NCHEM.2517, 10.1038/nchem.2517];[10.1038/NCHEMBIO.277, 10.1038/nchembio.277]
MRC Lab Mol Biol
Arangundy-Franklin, S;Holliger, P;Houlihan, G
Houlihan, G: MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
Houlihan, Gillian
MC_U105178804
89
null
UK
MRC Lab Mol Biol
Houlihan, Gillian
null
COMBINATORIAL SELECTION;CRYSTAL-STRUCTURE;DIRECTED EVOLUTION;DNA-POLYMERASE;ENZYMATIC-SYNTHESIS;IN-VITRO SELECTION;NUCLEIC-ACIDS;REVERSE-TRANSCRIPTASE;SEMISYNTHETIC ORGANISM;T7 RNA-POLYMERASE
Houlihan, Gillian; Arangundy-Franklin, Sebastian; Holliger, Philipp;
null
MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
1879-0429
null
null
1995;1997;1998;2000;2001;2002;2004;2005;2006;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
34
MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
Curr. Opin. Biotechnol.
Holliger, Philipp
ELSEVIER SCI LTD
,;a;acids;advanced;allow;alphabet;analogs;and;as;backbone;basepairs;biology;build;by;capable;capacity;chemical;chemistry;concomitantly;conjunction;crosstalk;dedicated;design;determinants;discovery;engineering;evolution;exchange;expand;exploration;field;for;function;genetic;genetics;given;has;here;in;information;investigation;is;lines;modified;moieties;molecular;natural;new;novel;nucleic;nucleobase;nucleotide;of;organic;polymerases;polymers;probed;progress;propagation;protein;recent;reverse;ring;rise;specifically;storage;sugar;summarize;synthesis;synthetic;system;systematically;templated;that;the;these;to;transcription;two;unnatural;utilizing;variation;we;well;with
MRC Lab Mol Biol
Organic chemistry has systematically probed the chemical determinants of function in nucleic acids by variation to the nucleobase, sugar ring and backbone moieties to build synthetic genetic polymers. Concomitantly, protein engineering has advanced to allow the discovery of polymerases capable of utilizing modified nucleotide analogs. A conjunction of these two lines of investigation in nucleotide chemistry and molecular biology has given rise to a new field of synthetic genetics dedicated to the exploration of the capacity of these novel, synthetic nucleic acids for the storage and propagation of genetic information, for evolution and for crosstalk, that is, information exchange with the natural genetic system. Here we summarize recent progress in synthetic genetics, specifically in the design of novel unnatural basepairs to expand the genetic alphabet as well as progress in engineering polymerases capable of templated synthesis, reverse transcription and evolution of synthetic genetic polymers.
Y-6197-2019
COMBINATORIAL SELECTION;CRYSTAL-STRUCTURE;DIRECTED EVOLUTION;DNA-POLYMERASE;ENZYMATIC-SYNTHESIS;IN-VITRO SELECTION;NUCLEIC-ACIDS;REVERSE-TRANSCRIPTASE;SEMISYNTHETIC ORGANISM;T7 RNA-POLYMERASE
3
null
null
12
COMBINATORIAL SELECTION;CRYSTAL-STRUCTURE;directed evolution;DNA-POLYMERASE;ENZYMATIC-SYNTHESIS;IN-VITRO SELECTION;NUCLEIC-ACIDS;REVERSE-TRANSCRIPTASE;SEMISYNTHETIC ORGANISM;T7 RNA-POLYMERASE
WOS:000418313200023
MRC Lab Mol Biol, Cambridge, England
UK
2,017
null
null
null
null
English
null
ACCOUNTS CHEM RES;ACS CHEM BIOL;ACS SYNTH BIOL;ANAL BIOANAL CHEM;ANGEW CHEM INT EDIT;ANNU REV BIOCHEM;APPL MICROBIOL BIOT;BIOCHEM BIOPH RES CO;BIOCHEMISTRY-US;BIOMATERIALS;CELL;CHEM BIODIVERS;CHEM BIOL;CHEMBIOCHEM;COLD SPRING HARBOR P;COLD SPRING HERB PER;CURR OPIN CHEM BIOL;CURR PROTOC NUCL ACI;EMBO J;ESSAYS BIOCHEM;FRONT MICROBIOL;J AM CHEM SOC;J BIOL CHEM;J BIOTECHNOL;J MOL BIOL;J SYST CHEM;MOL BIOL EVOL;MOL BIOSYST;NAT BIOTECHNOL;NAT CHEM;NAT CHEM BIOL;NAT COMMUN;NAT REV DRUG DISCOV;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;POLYM ENG PCR SEQUEN;RNA BIOL;SCIENCE;TETRAHEDRON
Arangundy-Franklin, Sebastian;Holliger, Philipp;Houlihan, Gillian
2024-03-11 ER
Ablasser, A;Anosova, I;Benner, S A;Brakmann, S;Brown, J A;Burmeister, P E;Chelliserrykattil, J;Chen, C Y;Chen, T;Chen, T J;Cozens, C;Delespaul, W;Dunn, M R;Elle, I C;Ellefson, J W;Fa, M;Ferreira-Bravo, I A;Friedman, A D;Gandham, S H A;Gao, P;Gao, Y;Gelinas, A D;Georgiadis, M M;Ghadessy, F J;Gold, L;Hagiwara, K;Herdewijn, P;Hollenstein, M;Horhota, A;Ibach, J;Ichida, J K;Keefe, A D;Khanal, A;Kimoto, M;Koshkin, A A;Kreil, G;Kunkel, T A;Laos, R;Larsen, A C;Li, L;Loakes, D;Maiti, M;Malyshev, D A;Matsunaga, K;Matsuura, M F;Mauer, J;Meyer, A J;Meyer, C;Mi, J;Millar, D;Murciano-Calles, J;Ng, E W M;Oberthür, D;Ong, J L;Padilla, R;Pech, A;Pinheiro, V B;Schultz, H J;Schöning, K U;Sefah, K;Sheng, J;Somasunderam, A;Sousa, R;Staiger, N;Svobodova, M;Szostak, J W;Taylor, A I;Tolle, F;Torres, L;Wang, Z M;Wlotzka, B;Xia, G;Yu, H Y;Zhang, L K;Zhang, L Q;Zhang, Y K;Zhou, J H;Zhu, B
FQ4FN
Cambridge, England
36
null
1
null
28,601,700
Arangundy-Franklin, Sebastian;Holliger, Philipp;Houlihan, Gillian
CURR OPIN BIOTECH
Cambridge, England
Blanchard, A E;Liao, C;Lu, T
10.1038/s41564-017-0022-5
null
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
3i566u6e446r691961l674t5m5gh1d384t2i24
An integrative circuit-host modelling framework for predicting synthetic gene network behaviours
Univ Illinois
null
Lu, T (corresponding author), Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA.;Lu, T (corresponding author), Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA.;Lu, T (corresponding author), Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.;Lu, T (corresponding author), Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
null
Blanchard, Andrew E;Liao, Chen;Lu, Ting
Microbiology
National Science Foundation [1553649, 1227034]; Office of Naval Research [N000141612525]; American Heart Association [12SDG12090025]; Brain and Behavior Research Foundation (NARSAD Young Investigator Award); National Center for Supercomputing Applications (Faculty Fellowship); Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1553649] Funding Source: National Science Foundation; Div Of Engineering Education and Centers; Directorate For Engineering [1227034] Funding Source: National Science Foundation; U.S. Department of Defense (DOD) [N000141612525] Funding Source: U.S. Department of Defense (DOD)
WOS
Lu, T
Univ Illinois, Urbana, IL USA
2
an;behaviours;circuit-host;for;Framework;gene;integrative;modelling;network;predicting;synthetic
1
Liao, Chen
NATURE PUBLISHING GROUP
Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA;Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Dept Phys, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Phys, Urbana, IL 61801 USA
Article
Univ Illinois
LONDON
null
null
Univ Illinois
American Heart Association;Brain and Behavior Research Foundation (NARSAD Young Investigator Award);Direct For Biological Sciences;Directorate For Engineering;Div Of Engineering Education and Centers;Div Of Molecular and Cellular Bioscience;National Center for Supercomputing Applications (Faculty Fellowship);National Science Foundation;Office of Naval Research;U.S. Department of Defense (DOD)
Lu, T (corresponding author), Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Dept Phys, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA.
1666
Blanchard, Andrew E;Liao, Chen;Lu, Ting
27
4
417,976,600,017
American Heart Association [12SDG12090025];Brain and Behavior Research Foundation (NARSAD Young Investigator Award);Direct For Biological Sciences;Directorate For Engineering [1227034] Funding Source: National Science Foundation;Div Of Engineering Education and Centers;Div Of Molecular and Cellular Bioscience [1553649] Funding Source: National Science Foundation;National Center for Supercomputing Applications (Faculty Fellowship);National Science Foundation [1553649, 1227034];Office of Naval Research [N000141612525];U.S. Department of Defense (DOD) [N000141612525] Funding Source: U.S. Department of Defense (DOD)
USA
NATURE MICROBIOLOGY
USA;USA.;
null
null
Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA
2058-5276
Blanchard, A E;Liao, C;Lu, T
DEC
luting@illinois.edu
integrative circuit-host modelling framework;synthetic gene network behaviours
3
J
Microbiology
behaviours;bidirectional circuit-host coupling;BIOLOGY;challenge;circuit behaviours;circuit-host interactions;CIRCUITS;complex interdependence;detailed kinetic module;dynamic resource partitioning;DYNAMICS;ESCHERICHIA-COLI;exogenous circuits;experimental data;expression;extended version;foreign gene overexpression;gene circuit behaviours;gene circuit modelling framework;Gene circuits;growth-modulating feedback;GROWTH-RATE;host;host physiology;IN-VIVO;integrative circuit-host modelling framework;lack;large set;leading cause;mechanistic description;multilayered circuit-host coupling;multiple factors;one fundamental challenge;population structure;PPGPP;PROTEIN-SYNTHESIS;quantitative understanding;rational design;single-cell dynamics;SOURCE SHIFT-DOWN;spatial ecology;synthetic biology;synthetic gene network behaviours;synthetic gene networks;system-specific interactions;toggle switch;toggle switch across scales;training;TRANSCRIPTION INITIATION;utility
Liao, C
BIOLOGY;ESCHERICHIA-COLI;EXPRESSION;GROWTH-RATE;IN-VIVO;PPGPP;PROTEIN-SYNTHESIS;SOURCE SHIFT-DOWN;toggle switch;TRANSCRIPTION INITIATION
1658
[Liao, Chen; Lu, Ting] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Liao, Chen; Blanchard, Andrew E.; Lu, Ting] Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA. [Blanchard, Andrew E.; Lu, Ting] Univ Illinois, Dept Phys, Urbana, IL 61801 USA. [Lu, Ting] Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA.
This work was supported by the National Science Foundation (No. 1553649 and 1227034), the Office of Naval Research (No. N000141612525), the American Heart Association (No. 12SDG12090025), the Brain and Behavior Research Foundation (NARSAD Young Investigator Award), and the National Center for Supercomputing Applications (Faculty Fellowship).
behaviours;bidirectional circuit-host coupling;challenge;circuit behaviours;circuit-host interactions;circuits;complex interdependence;detailed kinetic module;dynamic resource partitioning;dynamics;exogenous circuits;experimental data;extended version;foreign gene overexpression;gene circuit behaviours;gene circuit modelling framework;gene circuits;growth-modulating feedback;host;host physiology;lack;large set;leading cause;mechanistic description;multilayered circuit-host coupling;multiple factors;one fundamental challenge;population structure;quantitative understanding;rational design;single-cell dynamics;spatial ecology;synthetic biology;synthetic gene networks;system-specific interactions;toggle switch across scales;training;utility
10.1002/biot.201200085;10.1006/jmbi.2000.4327;10.1016/0022-2836(71)90336-6;10.1016/0734-9750(95)00004-A;10.1016/j.cbpa.2013.09.012;10.1016/j.cell.2004.07.009;10.1016/j.cell.2009.04.048;10.1016/j.cell.2009.10.025;10.1016/j.cell.2009.12.001;10.1016/j.cell.2012.05.044;10.1016/j.cell.2014.02.033;10.1016/j.febslet.2008.02.057;10.1016/S1097-2765(03)00266-1;10.1021/j100540a008;10.1038/35002125;10.1038/35002131;10.1038/463288a;10.1038/468889a;10.1038/msb.2013.14;10.1038/msb4100173;10.1038/nature03461;10.1038/nature10317;10.1038/nature11478;10.1038/nbt.1591;10.1038/nchembio.218;10.1038/ncomms15128;10.1038/nrg2775;10.1039/c5ib00275c;10.1073/pnas.0706115104;10.1073/pnas.0804953105;10.1073/pnas.1416533112;10.1073/pnas.1421138111;10.1099/00221287-19-3-592;10.1099/mic.0.26560-0;10.1111/j.1365-2958.2008.06229.x;10.1111/j.1462-2920.2010.02357.x;10.1126/science.1192588;10.1126/science.1206843;10.1126/science.1237435;10.1128/AAC.34.1.111;10.1128/JB.131.1.18-29.1977;10.1128/JB.131.1.7-17.1977;10.1128/jb.177.6.1497-1504.1995;10.1128/MMBR.55.2.316-333.1991;10.1146/annurev.micro.62.081307.162903;10.1186/1741-7007-4-30;10.1186/s12918-015-0188-5;[10.1038/NMETH.2926, 10.1038/nmeth.2926]
Univ Illinois
Blanchard, A E;Liao, C;Lu, T
Liao, C: Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA
null
1227034;12SDG12090025;1553649;N000141612525
50
null
USA
Univ Illinois
Liao, Chen
null
BIOLOGY;ESCHERICHIA-COLI;EXPRESSION;GROWTH-RATE;IN-VIVO;PPGPP;PROTEIN-SYNTHESIS;SOURCE SHIFT-DOWN;TOGGLE SWITCH;TRANSCRIPTION INITIATION
Liao, Chen; Blanchard, Andrew E.; Lu, Ting;
null
Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA;Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA;Univ Illinois, Dept Phys, Urbana, IL 61801 USA
Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA;Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA;Univ Illinois, Dept Phys, Urbana, IL 61801 USA
null
null
12
1958;1971;1975;1977;1990;1991;1995;2000;2001;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
54
Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA;Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA;Univ Illinois, Dept Phys, Urbana, IL 61801 USA
NAT. MICROBIOL
Lu, Ting
NATURE PUBLISHING GROUP
,;a;able;accurately;across;advances;also;altered;among;an;and;applied;arises;behaviours;benefits;bidirectional;biology;both;but;by;capture;cause;challenge;circuit;circuit-host;circuits;coarse-grained;complex;concerning;consists;coupling;data;demonstrate;describe;description;design;detailed;dynamic;dynamics;ecology;engineered;examine;exogenous;experimental;explicitly;extended;factors;feedback;following;foreign;framework;from;fundamental;further;gene;generic;growth-modulating;here;host;in;including;integrates;interactions;interdependence;involves;is;its;kinetic;lack;large;leading;mechanistic;modelling;module;multilayered;multiple;networks;of;one;our;overexpression;partitioning;physiology;population;predict;present;qualitatively;quantitative;rational;resource;revealed;scales;set;showed;single-cell;spatial;structure;switch;synthetic;system-specific;systematically;that;the;their;this;through;to;toggle;tools;training;understanding;using;utility;version;was;we;which;whose;with;work
Univ Illinois
One fundamental challenge in synthetic biology is the lack of quantitative tools that accurately describe and predict the behaviours of engineered gene circuits. This challenge arises from multiple factors, among which the complex interdependence of circuits and their host is a leading cause. Here we present a gene circuit modelling framework that explicitly integrates circuit behaviours with host physiology through bidirectional circuit-host coupling. The framework consists of a coarse-grained but mechanistic description of host physiology that involves dynamic resource partitioning, multilayered circuit-host coupling including both generic and system-specific interactions, and a detailed kinetic module of exogenous circuits. We showed that, following training, the framework was able to capture and predict a large set of experimental data concerning the host and its foreign gene overexpression. To demonstrate its utility, we applied the framework to examine a growth-modulating feedback circuit whose dynamics is qualitatively altered by circuit-host interactions. Using an extended version of the framework, we further systematically revealed the behaviours of a toggle switch across scales from single-cell dynamics to population structure and to spatial ecology. This work advances our quantitative understanding of gene circuit behaviours and also benefits the rational design of synthetic gene networks.
null
BIOLOGY;ESCHERICHIA-COLI;EXPRESSION;GROWTH-RATE;IN-VIVO;PPGPP;PROTEIN-SYNTHESIS;SOURCE SHIFT-DOWN;TOGGLE SWITCH;TRANSCRIPTION INITIATION
1
null
null
9
ESCHERICHIA-COLI;BIOLOGY;EXPRESSION;GROWTH-RATE;IN-VIVO;PPGPP;PROTEIN-SYNTHESIS;SOURCE SHIFT-DOWN;toggle switch;TRANSCRIPTION INITIATION
WOS:000417976600017
Univ Illinois, Urbana, IL USA
USA
2,017
null
0000-0001-8474-1196
null
null
English
null
ANNU REV MICROBIOL;ANTIMICROB AGENTS CH;BIOTECHNOL ADV;BIOTECHNOL J;BMC BIOL;BMC SYST BIOL;CELL;CURR OPIN CHEM BIOL;ECOSAL PLUS;ENVIRON MICROBIOL;FEBS LETT;INTEGR BIOL-UK;J BACTERIOL;J BIOL CHEM;J GEN MICROBIOL;J MOL BIOL;J PHYS CHEM-US;MICROBIOL REV;MICROBIOL-SGM;MOL CELL;MOL MICROBIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT REV GENET;NATURE;P NATL ACAD SCI USA;SCIENCE
Blanchard, Andrew E;Liao, Chen;Lu, Ting
2024-03-11 ER
Anderson, J C;Arkin, A P;Barker, M M;Basu, S;Blanchard, A E;Bollenbach, T;Bremer H.;Brophy, J A N;Cardinale, S;Chopra, I;Cox, R A;Deris, J B;Dong, H J;Elowitz, M;Elowitz, M B;Friesen, J D;Gardner, T S;Gerosa, L;Gillespie, D T;Glick, B R;Hartl, F U;Johnsen, K;Karpinets, T V;Karr, J R;Khalil, A S;Klumpp, S;Koch, A L;Kwok, R;Li, G W;Lu, T;Lu, T K;Maitra, A;Marr, A G;Molin, S;Murray, H D;Paul, B J;Peralta-Yahya, P P;Potrykus, K;Ruder, W C;Schaechter, M;Scott, M;Tabor, J J;Tan, C;Tozaki, H;Traxler, M F;Venturelli, O S;Weisse, A Y;Zhang, C
FP9NU
Urbana, IL USA;Urbana, IL USA.
61
null
1
null
28,947,816
Blanchard, Andrew E;Liao, Chen;Lu, Ting
NAT MICROBIOL
Urbana, IL USA
Cambray, G;Cardinale, S
10.1186/s12918-017-0494-1
112
CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
35gq3k23o63156o5v1kx1k06f1e422m4i4s
Genome-wide analysis of <i>E</i>. <i>coli</i> cell-gene interactions
Univ Calif Berkeley
null
Cardinale, S (corresponding author), Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Bldg 220, DK-2800 Lyngby, Denmark.;Cardinale, S (corresponding author), Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
null
Cambray, G;Cardinale, S
Mathematical & Computational Biology
National Science Foundation as part of the Synthetic Biology Engineering Research Center [04570/0540879]; Novo Nordisk Foundation (NNF) [11355-444]; Human Frontier Science Program [LT000873/2011-L]
WOS
Cardinale, S
Tech Univ Denmark, Lyngby, Denmark;Univ Calif Berkeley, Berkeley, CA USA;Univ Montpellier, Montpellier, France
11
<i>E</i>;Analysis;cell-gene;genome-wide;i>coli</i>;interactions;of
3
Cambray, Guillaume;Cardinale, Stefano
BMC
Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Bldg 220, DK-2800 Lyngby, Denmark;Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA;Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA;Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.; Cardinale, S (corresponding author), Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Bldg 220, DK-2800 Lyngby, Denmark;Univ Montpellier, INRA, DGIMI, Montpellier, France
Article
Tech Univ Denmark;Univ Calif Berkeley
LONDON
null
null
Tech Univ Denmark;Univ Calif Berkeley;Univ Montpellier
Human Frontier Science Program;National Science Foundation as part of the Synthetic Biology Engineering Research Center;Novo Nordisk Foundation (NNF)
Cardinale, S (corresponding author), Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.; Cardinale, S (corresponding author), Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Bldg 220, DK-2800 Lyngby, Denmark.
null
Cambray, G;Cardinale, S
8
4
416,045,700,001
Human Frontier Science Program [LT000873/2011-L];National Science Foundation as part of the Synthetic Biology Engineering Research Center [04570/0540879];Novo Nordisk Foundation (NNF) [11355-444]
Denmark;France;USA
BMC SYSTEMS BIOLOGY
Denmark;USA.;
null
null
Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
null
Cambray, G;Cardinale, S
NOV 23
cardinale.stefano@gmail.com
<i>E</i>;genome-wide analysis;i>coli</i> cell-gene interactions
2
J
Mathematical & Computational Biology
3822 single-gene deletion strains;<i>E</i>;background;biological circuits;BIOLOGY;Biosynthesis (DB) system led;cell division;Cell growth;cell size;cellular endogenous systems;cellular functions;cellular size;Cellular systems;conclusions;contrast;development;disruptions;distinct primary influence;division;dual fluorescent reporter gene;dual impact;effect;Energy;ESCHERICHIA-COLI;existence;expression;expression-specific;FEEDBACK;feedbacks;foundations;functions;gene disruptions proximally affect one component;gene expression;gene-specific effects;generic Size-Expression interaction;genes;genome-wide analysis;growth;high-expression phenotype;high-throughput screening methods;i>coli</i> cell-gene interactions;KEIO collection;KEIO gene knockouts;large-cell;low-expression phenotypes;Membrane;model prokaryote Escherichia coli;Motility (MM) system;number;perturbations;physiological systems;Positive feedback;predictable genetic parts;protein synthesis;pursuit;putting;recent years;regression analyses;reliability;results;ribosomal content;Ribosome (EPR) system;ribosome function;single cells via flow cytometry;Size-Expression interaction;Size-Expression map;small-cell;smaller cells;standardization;study;synthetic;synthetic biology;Synthetic gene expression;synthetic genes;systematic perturbations;systematic understanding;three systems;tight control;TRANSCRIPTION;whole-cell models;widespread across cell systems
Cardinale, S
BIOLOGY;Cell growth;Cellular systems;ESCHERICHIA-COLI;EXPRESSION;KEIO gene knockouts;Positive feedback;Synthetic gene expression;TRANSCRIPTION
null
[Cardinale, S.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. [Cardinale, S.] Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Bldg 220, DK-2800 Lyngby, Denmark. [Cambray, G.] Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA. [Cambray, G.] Univ Montpellier, INRA, DGIMI, Montpellier, France.
This work was funded by the National Science Foundation as part of the Synthetic Biology Engineering Research Center grant number 04570/0540879. SC also acknowledges funding from the Novo Nordisk Foundation (NNF) grant no. 11355-444 "Biobase". GC acknowledges funding by the Human Frontier Science Program (LT000873/2011-L).
3822 single-gene deletion strains;background;biological circuits;Biosynthesis (DB) system led;cell division;cell growth;cell size;cellular endogenous systems;cellular functions;cellular size;conclusions;contrast;development;disruptions;distinct primary influence;division;dual fluorescent reporter gene;dual impact;effect;Energy;existence;expression;expression-specific;Feedback;feedbacks;foundations;functions;gene disruptions proximally affect one component;gene expression;gene-specific effects;generic Size-Expression interaction;genes;genome-wide analysis;growth;high-expression phenotype;high-throughput screening methods;KEIO collection;large-cell;low-expression phenotypes;Membrane;model prokaryote Escherichia coli;Motility (MM) system;number;perturbations;physiological systems;positive feedback;predictable genetic parts;protein synthesis;pursuit;putting;recent years;regression analyses;reliability;results;ribosomal content;Ribosome (EPR) system;ribosome function;single cells via flow cytometry;Size-Expression interaction;Size-Expression map;small-cell;smaller cells;standardization;study;synthetic;synthetic biology;synthetic genes;systematic perturbations;systematic understanding;three systems;tight control;whole-cell models;widespread across cell systems
10.1002/biot.201200085;10.1016/j.cbpa.2013.09.012;10.1016/j.cell.2009.12.001;10.1016/j.celrep.2013.06.023;10.1016/j.celrep.2017.07.015;10.1016/j.cels.2016.04.004;10.1016/j.copbio.2014.01.001;10.1016/j.molcel.2016.11.007;10.1016/j.ymben.2013.01.006;10.1038/msb4100050;10.1038/nbt.3177;10.1038/nprot.2008.211;10.1093/bioinformatics/btr465;10.1128/JB.00259-17;10.1128/JB.130.1.212-222.1977;10.1128/jb.177.16.4696-4702.1995;10.1146/annurev.genet.38.072902.091347;10.1186/1754-1611-4-12;10.1186/1754-1611-7-22;10.15252/msb.20145379;[10.1038/NMETH.2404, 10.1038/nmeth.2404]
Univ Calif Berkeley
Cambray, G;Cardinale, S
Cardinale, S: Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
Cambray, Guillaume;Cardinale, Stefano
04570/0540879;11355-444;LT000873/2011-L
28
null
USA
Tech Univ Denmark;Univ Calif Berkeley;Univ Montpellier
Cardinale, S
Green Published, gold, Green Submitted
BIOLOGY;ESCHERICHIA-COLI;EXPRESSION;TRANSCRIPTION
Cardinale, S.; Cambray, G.;
null
Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Bldg 220, DK-2800 Lyngby, Denmark;Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA;Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA;Univ Montpellier, INRA, DGIMI, Montpellier, France
Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Bldg 220, DK-2800 Lyngby, Denmark;Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA;Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA;Univ Montpellier, INRA, DGIMI, Montpellier, France
1752-0509
Cell growth;Cellular systems;KEIO gene knockouts;Positive feedback;Synthetic gene expression
null
1977;1995;1996;1998;2000;2003;2004;2006;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
2
Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Bldg 220, DK-2800 Lyngby, Denmark;Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
BMC Syst. Biol.
Cambray, G
BMC
(DB);(EPR);(MM);,;3822;:;a;achieved;across;advances;affect;affected;all;an;analyses;analysis;and;aspects;associated;background;between;biological;biology;biosynthesis;both;broadly;by;caused;cell;cells;cellular;circuits;coli;collection;component;comprised;conclusions;construct;content;contrast;control;cytometry;deleted;deletion;describe;design;development;discriminate;disruptions;distinct;division;dual;each;effect;effects;elucidate;endogenous;energy;Escherichia;even;existence;expression;expression-specific;feedback;feedbacks;finally;flow;fluorescent;for;forward;found;foundations;function;functions;gene;gene-specific;generic;genes;genetic;genome-wide;growth;has;high-expression;high-throughput;how;however;impact;in;indirectly;influence;inserting;interaction;interacts;into;is;it;KEIO;large-cell;led;low-expression;map;mapped;measured;Membrane;methods;model;models;modulate;more;most;motility;not;number;of;on;one;onto;parts;perturbations;phenotype;phenotypes;physiological;positive;possible;predict;predictable;predominantly;presents;primary;prokaryote;propagates;protein;provides;proximally;pursuit;putting;quantified;recent;regression;reliability;reliably;reporter;results;ribosomal;Ribosome;screening;single;single-gene;size;Size-Expression;small-cell;smaller;specifically;standardization;still;strains;study;swarming;synthesis;synthetic;system;systematic;systems;that;the;therefore;this;though;three;through;tight;to;ultimately;understanding;used;via;was;we;were;whole-cell;widespread;with;work;years
Tech Univ Denmark;Univ Calif Berkeley
Background: The pursuit of standardization and reliability in synthetic biology has achieved, in recent years, a number of advances in the design of more predictable genetic parts for biological circuits. However, even with the development of high-throughput screening methods and whole-cell models, it is still not possible to predict reliably how a synthetic genetic construct interacts with all cellular endogenous systems. This study presents a genome-wide analysis of how the expression of synthetic genes is affected by systematic perturbations of cellular functions. We found that most perturbations modulate expression indirectly through an effect on cell size, putting forward the existence of a generic Size-Expression interaction in the model prokaryote Escherichia coli. Results: The Size-Expression interaction was quantified by inserting a dual fluorescent reporter gene construct into each of the 3822 single-gene deletion strains comprised in the KEIO collection. Cellular size was measured for single cells via flow cytometry. Regression analyses were used to discriminate between expression-specific and gene-specific effects. Functions of the deleted genes broadly mapped onto three systems with distinct primary influence on the Size-Expression map. Perturbations in the Division and Biosynthesis (DB) system led to a large-cell and high-expression phenotype. In contrast, disruptions of the Membrane and Motility (MM) system caused small-cell and low-expression phenotypes. The Energy, Protein synthesis and Ribosome (EPR) system was predominantly associated with smaller cells and positive feedback on ribosome function. Conclusions: Feedback between cell growth and gene expression is widespread across cell systems. Even though most gene disruptions proximally affect one component of the Size-Expression interaction, the effect therefore ultimately propagates to both. More specifically, we describe the dual impact of growth on cell size and gene expression through cell division and ribosomal content. Finally, we elucidate aspects of the tight control between swarming, gene expression and cell growth. This work provides foundations for a systematic understanding of feedbacks between genetic and physiological systems.
A-9476-2015;F-4024-2014
BIOLOGY;ESCHERICHIA-COLI;EXPRESSION;TRANSCRIPTION
1
null
Cell growth;Cellular systems;KEIO gene knockouts;Positive feedback;Synthetic gene expression
8
ESCHERICHIA-COLI;BIOLOGY;CELL-GROWTH;Cellular systems;EXPRESSION;KEIO gene knockouts;Positive feedback;Synthetic gene expression;TRANSCRIPTION
WOS:000416045700001
Tech Univ Denmark, Lyngby, Denmark;Univ Calif Berkeley, Berkeley, CA USA;Univ Montpellier, Montpellier, France
Denmark;France;USA
2,017
null
0000-0003-0087-2469;0000-0003-4357-9246
null
null
English
null
ANNU REV GENET;APPL ENVIRON MICROB;BIOINFORMATICS;BioRxiv;BIOTECHNOL J;CELL;CELL REP;CELL SYST;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;ECOSAL PLUS;J BACTERIOL;J Biol Eng;METAB ENG;MOL CELL;MOL SYST BIOL;NAT BIOTECHNOL;NAT METHODS;NAT PROTOC;PRACTICAL APPROACH F;PRACTICAL SH CYTOMET
Cambray, G;Cardinale, S
2024-03-11 ER
[Anonymous];Arkin A. P.;Arkin, A P;Baba, T;Brunk, E;Cardinale, S;Castle S.;Dennis, P P;Frumkin, I;Hintsche, M;Huang, D W;Klumpp, S;Mutalik, V K;Ormerod M.;Paul, B J;Pruss, B M;Prüss, B M;Robertson, B R;Scott, M;Shin, S;Sleight Sean, C;Wanner, B L;Woodruff, L B A;Wu, C H;Zeitoun, R I
FN5KG
Berkeley, CA USA.;Lyngby, Denmark
3
null
3
null
29,169,395
Cambray, G;Cardinale, S
BMC SYST BIOL
Berkeley, CA USA;Lyngby, Denmark;Montpellier, France
Gemperlein, K;Hoffmann, M;Huo, L J;Müller, R;Petzke, L;Pilak, P;Wenzel, S C
10.1016/j.ymben.2017.09.009
null
525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
2bj6l4j3l595p29201d332w6240t14256kr3z
Synthetic biology approaches to establish a heterologous production system for coronatines
Univ Saarland
null
Wenzel, SC (corresponding author), Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany.;Wenzel, SC (corresponding author), Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany.
null
Gemperlein, Katja;Hoffmann, Michael;Huo, Liujie;Mueller, Rolf;Petzke, Lutz;Pilak, Patrick;Wenzel, Silke C
Biotechnology & Applied Microbiology
BASF SE
WOS
Wenzel, S C
BASF SE, Ludwigshafen, Germany;Saarland Univ, Saarbrucken, Germany;Shandong Univ Helmholtz Joint Inst Biotechnol, Qingdao, Peoples R China;Tech Univ Munich, Weihenstephan, Germany
44
a;approaches;biology;coronatines;Establish;for;Heterologous;production;synthetic;system;to
2
Huo, Liujie;Muller, Rolf
ACADEMIC PRESS INC ELSEVIER SCIENCE
BASF SE, D-67056 Ludwigshafen, Germany;Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany;Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany;Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany.; Wenzel, SC (corresponding author), Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany;Shandong Univ Helmholtz Joint Inst Biotechnol, Qingdao, Peoples R China;Tech Univ Munich, Chair Biol Chem, D-85354 Freising Weihenstephan, Weihenstephan, Germany;Tech Univ Munich, Munich Ctr Integrated Prot Sci CiPSM, D-85354 Freising Weihenstephan, Weihenstephan, Germany
Article
Univ Saarland
SAN DIEGO
null
null
BASF SE;Saarland Univ;Shandong Univ Helmholtz Joint Inst Biotechnol;Tech Univ Munich
BASF SE
Wenzel, SC (corresponding author), Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany.; Wenzel, SC (corresponding author), Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany.
222
Gemperlein, Katja;Hoffmann, Michael;Huo, Liujie;Mueller, Rolf;Petzke, Lutz;Pilak, Patrick;Wenzel, Silke C
20
6
416,513,600,023
BASF SE
China;Germany
METABOLIC ENGINEERING
Germany
null
null
Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany
1096-7176
Gemperlein, K;Hoffmann, M;Huo, L J;Müller, R;Petzke, L;Pilak, P;Wenzel, S C
NOV
silke.wenzel@helmholtz-hzi.de
coronatines;heterologous production system;synthetic biology approaches
7
J
Biotechnology & Applied Microbiology
>90 mg/l;additional engineering;amide bond;applied constructional design facilitated versatile pathway modifications;ARABIDOPSIS-THALIANA;ASSEMBLY-LINE;bicyclic polyketide moiety;BIOSYNTHETIC GENE-CLUSTER;CARRIER PROTEIN DOMAINS;CFA;CFA production platforms;COMPLETE GENOME SEQUENCE;constitutive PrpsH promoter;COR;COR biosynthesis;COR biosynthetic gene cluster;Coronafacic acid;coronafacic acid (CFA);coronamic acid (CMA);Coronatine;coronatine (COR);coronatines;derivatives;development;engineering;expression;expression strain;expression vector features;function;gene cluster composition production profiles;genetic information;heterologous COR;heterologous expression;heterologous production system;host;IMPACT;led;modifications;multiple virulence activities;native producer P. syringae pv;P. putida KT2440;p15Aori-based transposon backbone;phytotoxin;PHYTOTOXIN CORONATINE;plant stress hormone jasmonoyl-L-isoleucine;Polyketide synthase;production;promising CFA production yields;Pseudomonads;Pseudomonas syringae;PSEUDOMONAS-PUTIDA KT2440;PV. TOMATO DC3000;reconstituted;selected pathway proteins;several pathovars;studies;synthetic biology approaches;synthetic DNA fragments;Synthetic gene cluster;target compounds;tomato DC3000;unusual ethylcyclopropyl amino acid moiety;use;valuable information;via
Gemperlein, K
ARABIDOPSIS-THALIANA;ASSEMBLY-LINE;BIOSYNTHETIC GENE-CLUSTER;CARRIER PROTEIN DOMAINS;COMPLETE GENOME SEQUENCE;Coronafacic acid;Coronatine;heterologous expression;PHYTOTOXIN CORONATINE;Polyketide synthase;Pseudomonads;PSEUDOMONAS-PUTIDA KT2440;PV. TOMATO DC3000;Synthetic gene cluster
213
[Gemperlein, Katja; Hoffmann, Michael; Mueller, Rolf; Wenzel, Silke C.] Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany. [Gemperlein, Katja; Hoffmann, Michael; Mueller, Rolf; Wenzel, Silke C.] Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany. [Huo, Liujie] Shandong Univ Helmholtz Joint Inst Biotechnol, Qingdao, Peoples R China. [Pilak, Patrick] Tech Univ Munich, Munich Ctr Integrated Prot Sci CiPSM, D-85354 Freising Weihenstephan, Weihenstephan, Germany. [Pilak, Patrick] Tech Univ Munich, Chair Biol Chem, D-85354 Freising Weihenstephan, Weihenstephan, Germany. [Petzke, Lutz] BASF SE, D-67056 Ludwigshafen, Germany.
We thank Nestor Zaburannyi for analysis of Illumina sequence data. We also thank Hubert S. Bernauer and Gregor Zipf from ATG:biosynthetics GmbH for the competent service regarding COR gene cluster design and DNA synthesis. This work was generously funded by BASF SE, we gratefully acknowledge all members of the project consortium for constant support of this study.
>90 mg/l;additional engineering;amide bond;applied constructional design facilitated versatile pathway modifications;bicyclic polyketide moiety;CFA;CFA production platforms;constitutive PrpsH promoter;COR;COR biosynthesis;COR biosynthetic gene cluster;coronafacic acid (CFA);coronamic acid (CMA);coronatine (COR);derivatives;development;engineering;expression;expression strain;expression vector features;function;gene cluster composition production profiles;genetic information;heterologous COR;host;impact;led;modifications;multiple virulence activities;native producer P. syringae pv;P. putida KT2440;p15Aori-based transposon backbone;phytotoxin;plant stress hormone jasmonoyl-L-isoleucine;production;promising CFA production yields;Pseudomonas syringae;reconstituted;selected pathway proteins;several pathovars;studies;synthetic DNA fragments;target compounds;tomato DC3000;unusual ethylcyclopropyl amino acid moiety;use;valuable information;via
10.1006/plas.1997.1294;10.1007/s00203-005-0059-3;10.1007/s00253-004-1836-7;10.1007/s00253-014-5952-8;10.1016/0048-4059(82)90026-1;10.1016/0378-1119(94)00661-B;10.1016/j.cell.2006.06.054;10.1016/j.chembiol.2004.12.012;10.1016/j.chembiol.2006.09.014;10.1016/j.chembiol.2012.01.007;10.1016/j.micres.2012.09.006;10.1016/j.pbi.2008.05.004;10.1016/j.ymben.2015.11.001;10.1016/S0031-9422(00)80702-5;10.1016/S0031-9422(00)81049-3;10.1016/S0031-9422(00)85028-1;10.1016/S0040-4020(98)01002-3;10.1016/S0378-1119(01)00476-0;10.1021/bi061930j;10.1021/bi700243h;10.1021/cr0503097;10.1021/ja00444a067;10.1021/ja8077945;10.1021/ja9536330;10.1021/sb3000657;10.1038/nature03797;10.1038/nchembio.161;10.1038/nchembio.734;10.1046/j.1365-2958.1999.01249.x;10.1046/j.1462-2920.2002.00366.x;10.1071/BI9700585;10.1073/pnas.0409450102;10.1073/pnas.1731982100;10.1073/pnas.95.26.15469;10.1073/pnas.96.4.1645;10.1093/nar/gkn499;10.1094/MPMI-8-0165;10.1094/MPMI.2004.17.2.162;10.1099/00221287-146-10-2447;10.1099/mic.0.2008/018820-0;10.1101/PDB.PROT4022;10.1104/pp.114.239061;10.1111/J.1364-3703.2005.00311.X;10.1111/j.1462-2920.2011.02430.x;10.1111/j.1574-6968.1997.tb12625.x;10.1111/j.1751-7915.2009.00107.x;10.1128/AEM.01503-06;10.1128/AEM.02315-08;10.1128/JB.01352-12;10.1128/JB.134.3.1141-1156.1978;10.1128/jb.172.7.3859-3867.1990;10.1128/JB.186.1.35-42.2004;10.1128/MMBR.63.2.266-292.1999;10.1186/1471-2091-10-26
Saarland Univ
Gemperlein, K;Hoffmann, M;Huo, L J;Müller, R;Petzke, L;Pilak, P;Wenzel, S C
Gemperlein, K: Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany
Huo, Liujie;Muller, Rolf
null
56
null
Germany
BASF SE;Saarland Univ;Shandong Univ Helmholtz Joint Inst Biotechnol;Tech Univ Munich
Gemperlein, Katja
null
ARABIDOPSIS-THALIANA;ASSEMBLY-LINE;BIOSYNTHETIC GENE-CLUSTER;CARRIER PROTEIN DOMAINS;COMPLETE GENOME SEQUENCE;CORONAFACIC ACID;PHYTOTOXIN CORONATINE;POLYKETIDE SYNTHASE;PSEUDOMONAS-PUTIDA KT2440;PV. TOMATO DC3000
Gemperlein, Katja; Hoffmann, Michael; Huo, Liujie; Pilak, Patrick; Petzke, Lutz; Mueller, Rolf; Wenzel, Silke C.;
null
BASF SE, D-67056 Ludwigshafen, Germany;Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany;Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany;Shandong Univ Helmholtz Joint Inst Biotechnol, Qingdao, Peoples R China;Tech Univ Munich, Chair Biol Chem, D-85354 Freising Weihenstephan, Weihenstephan, Germany;Tech Univ Munich, Munich Ctr Integrated Prot Sci CiPSM, D-85354 Freising Weihenstephan, Weihenstephan, Germany
BASF SE, D-67056 Ludwigshafen, Germany;Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany;Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany;Shandong Univ Helmholtz Joint Inst Biotechnol, Qingdao, Peoples R China;Tech Univ Munich, Chair Biol Chem, D-85354 Freising Weihenstephan, Weihenstephan, Germany;Tech Univ Munich, Munich Ctr Integrated Prot Sci CiPSM, D-85354 Freising Weihenstephan, Weihenstephan, Germany
1096-7184
Coronafacic acid;Coronatine;heterologous expression;Polyketide synthase;Pseudomonads;Synthetic gene cluster
null
1970;1977;1978;1982;1984;1985;1986;1990;1995;1996;1997;1998;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2011;2012;2013;2014;2016
13
Saarland Univ, Dept Pharmaceut Biotechnol, D-66123 Saarbrucken, Germany;Saarland Univ, Helmholtz Ctr Infect Res, Helmholtz Inst Pharmaceut Res Saarland, Dept Microbial Nat Prod, D-66123 Saarbrucken, Germany
Metab. Eng.
Wenzel, Silke C
ACADEMIC PRESS INC ELSEVIER SCIENCE
(CFA);(CMA);(COR);,;>90;a;about;acid;activities;additional;aimed;amide;amino;an;and;applied;as;at;backbone;based;bicyclic;biosynthesis;biosynthetic;bond;by;CFA;cluster;composition;compounds;consists;constitutive;constructional;constructs;COR;coronafacic;coronamic;coronatine;DC3000;derivatives;design;designed;development;directed;DNA;engineering;establishing;ethylcyclopropyl;evaluated;expression;facilitated;features;for;fragments;from;function;gene;generation;genetic;heterologous;hormone;host;impact;in;including;information;is;it;its;jasmonoyl-L-isoleucine;KT2440;led;linked;mediates;mg/L;mimicking;modifications;moiety;multiple;native;obtained;of;on;our;P.;p15Aori-based;pathovars;pathway;phytotoxin;plant;platforms;polyketide;produced;producer;production;profiles;promising;promoter;proteins;PrpsH;Pseudomonas;putida;pv;reconstituted;represents;selected;several;strain;stress;structurally;studies;synthetic;syringae;target;the;to;tomato;towards;transposon;unusual;use;using;valuable;various;vector;versatile;via;virulence;was;we;were;which;with;yields
Saarland Univ
Coronatine (COR) represents a phytotoxin produced by several pathovars of Pseudomonas syringae. It mediates multiple virulence activities by mimicking the plant stress hormone jasmonoyl-L-isoleucine. Structurally, COR consists of a bicyclic polyketide moiety, coronafacic acid (CFA), which is linked via an amide bond to an unusual ethylcyclopropyl amino acid moiety, coronamic acid (CMA). In our studies, we aimed at establishing and engineering of heterologous COR and CFA production platforms using P. putida KT2440 as host. Based on genetic information of the native producer P. syringae pv. tomato DC3000 a COR biosynthetic gene cluster was designed and reconstituted from synthetic DNA fragments. The applied constructional design facilitated versatile pathway modifications and the generation of various expression constructs, which were evaluated for the production of CFA, COR and its derivatives. By modifications of the gene cluster composition production profiles were directed towards target compounds and valuable information about the function and impact of selected pathway proteins on COR biosynthesis were obtained. Additional engineering of expression vector features, including the use of the constitutive PrpsH promoter and a p15Aori-based transposon backbone, led to the development of an expression strain with promising CFA production yields of >90 mg/l.
B-1559-2008;GSN-6252-2022;L-6090-2019
ARABIDOPSIS-THALIANA;ASSEMBLY-LINE;BIOSYNTHETIC GENE-CLUSTER;CARRIER PROTEIN DOMAINS;COMPLETE GENOME SEQUENCE;CORONAFACIC ACID;PHYTOTOXIN CORONATINE;POLYKETIDE SYNTHASE;PSEUDOMONAS-PUTIDA KT2440;PV. TOMATO DC3000
1
null
Coronafacic acid;Coronatine;heterologous expression;Polyketide synthase;Pseudomonads;Synthetic gene cluster
10
ARABIDOPSIS-THALIANA;ASSEMBLY-LINE;BIOSYNTHETIC GENE-CLUSTER;CARRIER PROTEIN DOMAINS;COMPLETE GENOME SEQUENCE;Coronafacic acid;Coronatine;heterologous expression;PHYTOTOXIN CORONATINE;Polyketide synthase;Pseudomonads;PSEUDOMONAS-PUTIDA KT2440;PV. TOMATO DC3000;Synthetic gene cluster
WOS:000416513600023
BASF SE, Ludwigshafen, Germany;Saarland Univ, Saarbrucken, Germany;Shandong Univ Helmholtz Joint Inst Biotechnol, Qingdao, Peoples R China;Tech Univ Munich, Weihenstephan, Germany
China;Germany
2,017
null
0000-0002-1042-5665;0000-0002-1406-8466
null
null
English
null
ACS SYNTH BIOL;APPL ENVIRON MICROB;APPL MICROBIOL BIOT;ARCH MICROBIOL;AUST J BIOL SCI;BIOCHEMISTRY-US;BMC BIOCHEM;CELL;CHEM BIOL;CHEM REV;CURR OPIN PLANT BIOL;ENVIRON MICROBIOL;FEMS MICROBIOL LETT;GENE;J AM CHEM SOC;J BACTERIOL;J GEN MICROBIOL;J MOL MICROB BIOTECH;METAB ENG;MICROB BIOTECHNOL;MICROBIOL MOL BIOL R;MICROBIOL RES;MICROBIOL-SGM;MOL CLONING LAB MANU;MOL MICROBIOL;MOL PLANT MICROBE IN;MOL PLANT PATHOL;NAT CHEM BIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYSIOL PLANT PATHOL;PHYTOCHEMISTRY;PLANT PHYSIOL;PLASMID;TETRAHEDRON
Gemperlein, Katja;Hoffmann, Michael;Huo, Liujie;Mueller, Rolf;Petzke, Lutz;Pilak, Patrick;Wenzel, Silke C
2024-03-11 ER
Bakke, I;Bender, C L;Berg, L;Blatny, J M;Braun, Y;Brooks, D M;Buell, C R;Chai, Y;Chang, A C Y;Couch, R;Cui, J;Dayan, F E;Dudnik, A;Durland, R H;Fischbach, M A;Fonseca, S;Frank, S;Fu, J;Gemperlein, K;Gross, F;Ichihara, A;Jiralerspong, S;Katsir, L;Keane, P J;Kelly, W L;Kotowska, M;Liyanage, H;Loeschcke, A;Marqués, S;Melotto, M;Mitchell, R E;Mittal, S;Nelson, K E;Parry, R J;Patel, J;Perlova, O;Peñaloza-Vázquez, A;Quade, N;Ramel, C;Rangaswamy, V;Rubin, E J;Sambrook J.;Smirnova, A V;Strieter, E R;Vaillancourt, F H;Wenzel, S C;Worley, J N
FO1IX
Saarbrucken, Germany;Saarbrucken, Germany.
16
null
4
null
28,951,265
Gemperlein, Katja;Hoffmann, Michael;Huo, Liujie;Mueller, Rolf;Petzke, Lutz;Pilak, Patrick;Wenzel, Silke C
METAB ENG
Ludwigshafen, Germany;Qingdao, Peoples R China;Saarbrucken, Germany;Weihenstephan, Germany
Chen, W C W;Higashikuni, Y;Lu, T K
10.1016/j.copbio.2017.06.011
null
THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
1j1f5h4t3c572kd6c5j4f5c246j5v28vp6j71
Advancing therapeutic applications of synthetic gene circuits
MIT
null
Lu, TK (corresponding author), MIT, Dept Biol Engn, Cambridge, MA 02139 USA.;Lu, TK (corresponding author), MIT, Elect Res Lab, Cambridge, MA 02139 USA.
null
Chen, William C W;Higashikuni, Yasutomi;Lu, Timothy K
Biochemical Research Methods;Biotechnology & Applied Microbiology
Japan Heart Foundation; Uehara Memorial Foundation; NIH Ruth L Kirschstein NRSA postdoctoral fellowship [5T32HL007208]; American Heart Association Collaborative Sciences Award [14CSA20500002]
WOS
Lu, T K
Massachusetts Gen Hosp, Boston, MA USA;MIT, Cambridge, MA USA
47
advancing;applications;circuits;gene;of;synthetic;therapeutic
1
HIGASHIKUNI, YASUTOMI
ELSEVIER SCI LTD
Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;MIT, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Dept Biol Engn, Cambridge, MA 02139 USA
Review
MIT
OXFORD
null
null
Elect Res Lab;Massachusetts Gen Hosp;MIT
American Heart Association Collaborative Sciences Award;Japan Heart Foundation;NIH Ruth L Kirschstein NRSA postdoctoral fellowship;Uehara Memorial Foundation
Lu, TK (corresponding author), MIT, Elect Res Lab, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
141
Chen, William C W;Higashikuni, Yasutomi;Lu, Timothy K
59
3
413,381,100,017
American Heart Association Collaborative Sciences Award [14CSA20500002];Japan Heart Foundation;NIH Ruth L Kirschstein NRSA postdoctoral fellowship [5T32HL007208];Uehara Memorial Foundation
USA
CURRENT OPINION IN BIOTECHNOLOGY
USA;USA.;
null
null
MIT, Elect Res Lab, Cambridge, MA 02139 USA
0958-1669
Chen, W C W;Higashikuni, Y;Lu, T K
OCT
timlu@mit.edu
advancing therapeutic applications;synthetic gene circuits
3
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
acid;advancing therapeutic applications;BACTERIA;biomedicine;Boolean logic gate circuits;cells;challenges;closed loop circuits;DESIGN;development;devices;disease;effector screening technologies;expression;extracellular environment;future opportunities;gene networks;homeostasis;inflammation;intracellular signaling;living cells;local delivery;mammalian cells;MICROBIOME;modified microbes;new sense-and-respond capabilities;novel therapeutic strategies;ORGANISMS;recent advances;regulatory elements;researchers;response;restoration;review;spatiotemporal control;specific functions;synthetic biology aims;synthetic gene circuits;T-CELLS;therapeutic applications;therapeutic molecules;tools
Higashikuni, Y
ACID;BACTERIA;DESIGN;DISEASE;EXPRESSION;HOMEOSTASIS;INFLAMMATION;MICROBIOME;T-CELLS;TOOLS
133
[Higashikuni, Yasutomi; Chen, William C. W.; Lu, Timothy K.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Higashikuni, Yasutomi; Chen, William C. W.; Lu, Timothy K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Chen, William C. W.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
YH was supported in part by the research fellowships from the Japan Heart Foundation and the Uehara Memorial Foundation. WC was supported by the NIH Ruth L Kirschstein NRSA postdoctoral fellowship (5T32HL007208). This work was supported by the American Heart Association Collaborative Sciences Award (14CSA20500002).
biomedicine;Boolean logic gate circuits;cells;challenges;closed loop circuits;development;devices;effector screening technologies;extracellular environment;future opportunities;gene networks;homeostasis;intracellular signaling;living cells;local delivery;mammalian cells;modified microbes;new sense-and-respond capabilities;novel therapeutic strategies;organisms;recent advances;regulatory elements;researchers;response;restoration;review;spatiotemporal control;specific functions;synthetic biology aims;synthetic gene circuits;therapeutic applications;therapeutic molecules
10.1002/anie.201507634;10.1002/anie.201507978;10.1002/biot.201400642;10.1002/biot.201600099;10.1016/j.addr.2016.04.006;10.1016/j.cell.2015.02.010;10.1016/j.cell.2016.01.011;10.1016/j.cell.2016.01.012;10.1016/j.cell.2016.09.011;10.1016/j.cell.2016.09.013;10.1016/j.cell.2017.03.041;10.1016/j.cell.2017.03.045;10.1016/j.cels.2015.06.001;10.1016/j.ejphar.2017.04.021;10.1016/j.it.2015.06.004;10.1016/j.jhep.2016.03.020;10.1016/j.jmb.2015.10.004;10.1016/j.molcel.2014.03.030;10.1016/j.neuron.2015.03.065;10.1016/j.pharmthera.2013.12.014;10.1016/j.tig.2014.09.004;10.1016/j.ymthe.2016.10.005;10.1016/S0140-6736(07)61128-3;10.1021/acschembio.6b00234;10.1021/sb400077j;10.1021/sb400128g;10.1021/sb500090b;10.1021/sb500173f;10.1038/boneres.2016.9;10.1038/mi.2013.73;10.1038/nature18930;10.1038/nbt.3301;10.1038/nbt.3326;10.1038/ncomms10624;10.1038/ncomms15028;10.1038/npp.2015.293;10.1038/nrd.2016.245;10.1038/nrendo.2013.193;10.1038/nrendo.2015.227;10.1038/srep18950;10.1039/c5mb00763a;10.1056/NEJMra1110560;10.1056/NEJMra1600266;10.1073/pnas.1508521112;10.1073/pnas.1514383113;10.1073/pnas.1517883113;10.1093/nar/gkw117;10.1097/MOG.0000000000000139;10.1098/rsif.2014.1000;10.1101/gad.284828.116;10.1111/j.1440-1746.2010.06549.x;10.1126/science.aab4077;10.1126/science.aac7341;10.1126/science.aaf4006;10.1126/scisignal.aaf7593;10.1126/scitranslmed.3005975;10.1126/scitranslmed.aac4964;10.1146/annurev-pharmtox-010814-124803;10.1152/physrev.00030.2013;10.1155/2015/375187;10.1172/JCI72517;10.1586/14760584.2015.997714;10.2337/db13-1236;10.2337/db14-0635;10.3748/wjg.v19.i25.3931;10.4161/hv.28549;[10.1038/NMETH.3585, 10.1038/nmeth.3585]
MIT
Chen, W C W;Higashikuni, Y;Lu, T K
Higashikuni, Y: MIT, Elect Res Lab, Cambridge, MA 02139 USA
Lu, Timothy K
14CSA20500002;5T32HL007208
69
null
USA
Massachusetts Gen Hosp;MIT
Higashikuni, Yasutomi
null
ACID;BACTERIA;DESIGN;DISEASE;EXPRESSION;HOMEOSTASIS;INFLAMMATION;MICROBIOME;T-CELLS;TOOLS
Higashikuni, Yasutomi; Chen, William C. W.; Lu, Timothy K.;
null
Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;MIT, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Cambridge, MA 02139 USA
Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;MIT, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Cambridge, MA 02139 USA
1879-0429
null
null
2007;2010;2011;2012;2013;2014;2015;2016;2017
19
MIT, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Cambridge, MA 02139 USA
Curr. Opin. Biotechnol.
Lu, Timothy K
ELSEVIER SCI LTD
,;addition;advances;aims;and;applications;as;be;biology;biomedicine;Boolean;can;capabilities;cells;challenges;circuits;closed;computing;control;delivery;design;designed;development;devices;discuss;effector;elements;enable;enabled;engineered;environment;extracellular;for;functions;future;gate;gene;genetically;has;homeostasis;in;including;into;intracellular;introduce;living;local;logic;loop;mammalian;many;microbes;modified;molecular;molecules;networks;new;novel;of;opportunities;or;organisms;perform;program;recent;regulatory;researchers;response;restoration;review;screening;sense-and-respond;signaling;spatiotemporal;specific;strategies;such;synthetic;technologies;the;therapeutic;this;to;used;we;well;which;will;with;would
MIT
Synthetic biology aims to introduce new sense-and-respond capabilities into living cells, which would enable novel therapeutic strategies. The development of regulatory elements, molecular computing devices, and effector screening technologies has enabled researchers to design synthetic gene circuits in many organisms, including mammalian cells. Engineered gene networks, such as closed loop circuits or Boolean logic gate circuits, can be used to program cells to perform specific functions with spatiotemporal control and restoration of homeostasis in response to the extracellular environment and intracellular signaling. In addition, genetically modified microbes can be designed as local delivery of therapeutic molecules. In this review, we will discuss recent advances in therapeutic applications of synthetic gene circuits, as well as challenges and future opportunities for biomedicine.
G-4267-2012
ACID;BACTERIA;DESIGN;DISEASE;EXPRESSION;HOMEOSTASIS;INFLAMMATION;MICROBIOME;T-CELLS;TOOL
3
null
null
9
ACID;BACTERIA;DESIGN;DISEASE;EXPRESSION;HOMEOSTASIS;INFLAMMATION;MICROBIOME;T-CELLS;TOOL
WOS:000413381100017
Massachusetts Gen Hosp, Boston, MA USA;MIT, Cambridge, MA USA
USA
2,017
null
0000-0002-2232-567X
null
null
English
null
ACS CHEM BIOL;ACS SYNTH BIOL;ADV DRUG DELIVER REV;ANGEW CHEM INT EDIT;ANNU REV PHARMACOL;BIOTECHNOL J;BONE RES;CELL;CELL SYST;COLD SPRING HARB PER;CURR OPIN GASTROEN;DIABETES;EUR J PHARMACOL;EXPERT REV VACCINES;GENE DEV;HUM VACC IMMUNOTHER;J CLIN INVEST;J GASTROEN HEPATOL;J HEPATOL;J MOL BIOL;J R SOC INTERFACE;LANCET;MOL BIOSYST;MOL CELL;MOL THER;MUCOSAL IMMUNOL;NAT BIOTECHNOL;NAT COMMUN;NAT METHODS;NAT REV DRUG DISCOV;NAT REV ENDOCRINOL;NATURE;NEURON;NEUROPSYCHOPHARMACOL;NEW ENGL J MED;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHARMACOL THERAPEUT;PHYSIOL REV;ROBBINS COTRAN PATHO;SCI REP-UK;SCI SIGNAL;SCI TRANSL MED;SCIENCE;STEM CELLS INT;TRENDS GENET;TRENDS IMMUNOL;WORLD J GASTROENTERO
Chen, William C W;Higashikuni, Yasutomi;Lu, Timothy K
2024-03-11 ER
Andries, O;Auslander S.;Ausländer, S;Bai, P;Bartalena, L;Beal, J;Bhatia, S N;Borrero, J;Bradley, R W;Braff, D;Chen, W C W;Chen, Z Y;Chovatiya, R;Daringer, N M;Din, M O;Duan, F F;Foo, J L;Gosselin, P;Griffiths, C E M;Hwang, I Y;Juillerat, A;Juillot, S;Kis, Z;Kotas, M E;Kumar, V;Lai, A C;Lim, B;Liu, K W;Lynch, S V;Marlow, G J;Maroun, C R;Martín, R;Mimee, M;Morsut, L;Mullur, R;Nakamura, T;Navarro, R;Neurath, M F;Nielsen, A A K;Niopek, D;Pardee, K;Polonsky, K S;Raman, S;Robert, S;Roybal, K T;Saxena, P;Schukur, L;Shi, Y;Shreiner, A B;Slomovic, S;Smole, A;Srivastava, S;Sun, X;Toure, M;Tuomilehto, J;Urban, D J;Vardy, E;Whitaker, W R;Wong, A S L;Wroblewska, L;Wu, C Y;Wu, M R;Xie, M;Xie, M Q
FK3JJ
Cambridge, MA USA;Cambridge, MA USA.
21
null
2
null
28,750,201
Chen, William C W;Higashikuni, Yasutomi;Lu, Timothy K
CURR OPIN BIOTECH
Boston, MA USA;Cambridge, MA USA
Boucher, N;Derbyshire, K M;Gray, T A;Judd, J;Van Roey, E
10.1128/JB.00410-17
e00410
1752 N ST NW, WASHINGTON, DC 20036-2904 USA
gz4ak561p9485w5i70d572k2v304d39576r
Application of Distributive Conjugal DNA Transfer in <i>Mycobacterium smegmatis</i> To Establish a Genome-Wide Synthetic Genetic Array
New York State Dept Hlth
null
Derbyshire, KM (corresponding author), New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA.;Derbyshire, KM (corresponding author), SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA.
null
Boucher, Nathalie;Derbyshire, Keith M;Gray, Todd A;Judd, Julius;Van Roey, Erik
Microbiology
NIAID [R21AI07258, R01AI097191]
WOS
Derbyshire, K M
New York State Dept Hlth, Albany, NY USA;SUNY Albany, Albany, NY USA
199
<i>Mycobacterium;a;application;Array;Conjugal;Distributive;DNA;Establish;genetic;genome-wide;in;of;smegmatis</i>;synthetic;to;Transfer
1
Judd, Julius
AMER SOC MICROBIOLOGY
New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA;New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA.; Derbyshire, KM (corresponding author), SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA;SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA
Article
New York State Dept Hlth;SUNY Albany
WASHINGTON
null
null
New York State Dept Hlth;SUNY Albany
NIAID
Derbyshire, KM (corresponding author), New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA.; Derbyshire, KM (corresponding author), SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA.
null
Boucher, Nathalie;Derbyshire, Keith M;Gray, Todd A;Judd, Julius;Van Roey, Erik
8
2
411,075,700,009
NIAID [R21AI07258, R01AI097191]
USA
JOURNAL OF BACTERIOLOGY
USA;USA.;
null
null
New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA
0021-9193
Boucher, N;Derbyshire, K M;Gray, T A;Judd, J;Van Roey, E
OCT
keith.derbyshire@health.ny.gov
<i>Mycobacterium smegmatis</i>;application;Distributive Conjugal DNA Transfer;Genome-Wide Synthetic Genetic Array
5
J
Microbiology
<i>Mycobacterium smegmatis</i>;advantage;analysis;application;arrayed library;chromosomal conjugation system;CHROMOSOMAL DNA;combination;combines mutations;conjugation;conserved hypothetical genes;conserved hypothetical protein annotations;defined mutations;Distributive Conjugal DNA Transfer;double mutant strains;essential process;esx3;fast-growing nonpathogenic species;feasibility;function;functions;fxbA;gene interactions;genes;genesencoding;genetic redundancy;genome-scale SGA;genome-wide scale;Genome-Wide Synthetic Genetic Array;great potential;high efficiency;high number;high-throughput mycobacterial SGA (mSGA) screen;hypothetical genes;IDENTIFICATION;identified novel;IMPORTANCE Mycobacterium smegmatis;individual donor;initial assignment;IRON;iron utilization pathways;known genes;M. smegmatis;model organism;molecular genetic approaches;mSGA;mutants;Mycobacteria;mycobacterial genomes;mycobacterial pathogens;mycobacterial pathways;mycobacterial species;Mycobacterium smegmatis;noncoding RNA (ncRNA);novel genetic interactions;obscure phenotypic effects;pathways;powerful approach;powerful genetic tool;proteins;query genes;RecA;recipient mutations;redundant biological pathways;redundant pathways;single-gene mutations;study;SURVIVAL;synthetic genetic array;synthetic genetic array (mSGA) approach;synthetic genetic arrays (SGAs);transposon mutants;TUBERCULOSIS;two gene products;two individual mutations;uncovering interactions
Judd, J
CHROMOSOMAL DNA;conjugation;IDENTIFICATION;IRON;iron utilization pathways;Mycobacteria;RecA;SURVIVAL;synthetic genetic array;TUBERCULOSIS
null
[Judd, Julius; Boucher, Nathalie; Van Roey, Erik; Gray, Todd A.; Derbyshire, Keith M.] New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA. [Gray, Todd A.; Derbyshire, Keith M.] SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA.
This work was supported by funding from NIAID R21AI07258 and R01AI097191. The Wadsworth Center Core Facilities performed the sequencing and bioinformatics and provided media.
advantage;analysis;arrayed library;chromosomal conjugation system;combination;combines mutations;conjugation;conserved hypothetical genes;conserved hypothetical protein annotations;defined mutations;double mutant strains;essential process;esx3;fast-growing nonpathogenic species;feasibility;function;functions;fxbA;gene interactions;genes;genesencoding;genetic redundancy;genome-scale SGA;genome-wide scale;great potential;high efficiency;high number;high-throughput mycobacterial SGA (mSGA) screen;hypothetical genes;identification;identified novel;IMPORTANCE Mycobacterium smegmatis;individual donor;initial assignment;known genes;M. smegmatis;model organism;molecular genetic approaches;mSGA;mutants;mycobacteria;mycobacterial genomes;mycobacterial pathogens;mycobacterial pathways;mycobacterial species;Mycobacterium smegmatis;noncoding RNA (ncRNA);novel genetic interactions;obscure phenotypic effects;pathways;powerful approach;powerful genetic tool;proteins;query genes;recA;recipient mutations;redundant biological pathways;redundant pathways;single-gene mutations;study;synthetic genetic array (mSGA) approach;synthetic genetic arrays (SGAs);transposon mutants;two gene products;two individual mutations;uncovering interactions
10.1016/j.cell.2005.08.031;10.1016/j.cell.2010.11.052;10.1016/j.mib.2009.11.006;10.1016/j.tube.2015.01.004;10.1038/nchembio.340;10.1038/ng1844;10.1038/NMETH.1240;10.1038/nmeth0908-759;10.1038/nmeth996;10.1046/j.1365-2958.1998.00818.x;10.1073/pnas.0404892101;10.1073/pnas.0503272102;10.1073/pnas.0603179103;10.1073/pnas.0900589106;10.1073/pnas.1514135112;10.1073/pnas.231275498;10.1093/nar/gkg595;10.1111/j.1365-2958.2005.04824.x;10.1111/j.1365-2958.2007.05935.x;10.1111/j.1365-2958.2008.06299.x;10.1126/science.1065810;10.1126/science.1106753;10.1126/science.1162609;10.1128/genomeA.00148-13;10.1128/JB.00024-09;10.1128/JB.00216-07;10.1128/JB.01222-07;10.1128/JB.181.11.3402-3408.1999;10.1128/JB.181.14.4266-4274.1999;10.1261/rna.034116.112;10.1371/journal.pbio.1001602;10.1371/journal.pgen.1002377;10.1371/journal.pgen.1004120;10.1371/journal.pgen.1005641;10.1371/journal.ppat.1002251;10.1371/journal.ppat.1003120;10.2144/000112601;[10.1038/nmeth.1239, 10.1038/NMETH.1239];[10.1039/B907407d, 10.1039/b907407d]
New York State Dept Hlth
Boucher, N;Derbyshire, K M;Gray, T A;Judd, J;Van Roey, E
Judd, J: New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA
null
R01AI097191;R21AI07258
40
null
USA
New York State Dept Hlth;SUNY Albany
Judd, Julius
Bronze, Green Published
CHROMOSOMAL DNA;IDENTIFICATION;IRON;SURVIVAL;TUBERCULOSIS
Judd, Julius; Boucher, Nathalie; Van Roey, Erik; Gray, Todd A.; Derbyshire, Keith M.;
null
New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA;SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA
New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA;SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA
1098-5530
conjugation;iron utilization pathways;Mycobacteria;RecA;synthetic genetic array
20
1991;1998;1999;2001;2003;2004;2005;2006;2007;2008;2009;2010;2011;2013;2014;2015
3
New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12201 USA;SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA
J. Bacteriol.
Derbyshire, Keith M
AMER SOC MICROBIOLOGY
(mSGA);(ncRNA);(SGAs);,;a;advantage;all;an;analysis;and;annotations;approach;approaches;are;array;arrayed;arrays;as;assigned;assignment;be;because;biological;both;but;by;can;choice;chromosomal;combination;combine;combined;combines;conjugation;conserved;define;defined;demonstrated;describe;donor;double;effects;efficiency;enables;essential;esx3;fast-growing;feasibility;for;found;function;functions;further;fxbA;gene;genes;genesencoding;genetic;genome-scale;genome-wide;genomes;great;had;harboring;has;here;hidden;high;high-throughput;hypothetical;identification;identified;identify;importance;importantly;in;individual;initial;interacting;interactions;is;it;known;lethal;library;linking;M.;many;may;model;molecular;most;mSGA;mutant;mutants;mutations;mycobacteria;mycobacterial;Mycobacterium;noncoding;nonpathogenic;normally;novel;number;obscure;of;offer;on;or;organism;other;pathogens;pathways;phenotypic;potential;powerful;predicted;process;products;protein;proteins;provide;query;recA;recipient;reduce;redundancy;redundant;RNA;scale;screen;separately;SGA;single-gene;smegmatis;species;strains;study;synthetic;synthetically;system;take;that;the;this;throughout;thus;to;tool;transposon;two;uncovering;using;viable;we;were;when;which;with;work
New York State Dept Hlth;SUNY Albany
Genetic redundancy can obscure phenotypic effects of single-gene mutations. Two individual mutations may be viable separately but are lethal when combined, thus synthetically linking the two gene products in an essential process. Synthetic genetic arrays (SGAs), in which defined mutations are combined, provide a powerful approach to identify novel genetic interactions and redundant pathways. A genome-scale SGA can offer an initial assignment of function to hypothetical genes by uncovering interactions with known genes or pathways. Here, we take advantage of the chromosomal conjugation system of Mycobacterium smegmatis to combine individual donor and recipient mutations on a genome-wide scale. We demonstrated the feasibility of a high-throughput mycobacterial SGA (mSGA) screen by using mutants of esx3, fxbA, and recA as query genes, which were combined with an arrayed library of transposon mutants by conjugation. The mSGA identified interacting genes that we had predicted and, most importantly, identified novel interacting genesencoding both proteins and a noncoding RNA (ncRNA). In combination with other molecular genetic approaches, the mSGA has great potential to both reduce the high number of conserved hypothetical protein annotations in mycobacterial genomes and further define mycobacterial pathways and gene interactions. IMPORTANCE Mycobacterium smegmatis is the model organism of choice for the study of mycobacterial pathogens, because it is a fast-growing nonpathogenic species harboring many genes that are conserved throughout mycobacteria. In this work, we describe a synthetic genetic array (mSGA) approach for M. smegmatis, which combines mutations on a genome-wide scale with high efficiency. Analysis of the double mutant strains enables the identification of interacting genes and pathways that are normally hidden by redundant biological pathways. The mSGA is a powerful genetic tool that enables functions to be assigned to the many conserved hypothetical genes found in all mycobacterial species.
null
CHROMOSOMAL DNA;IDENTIFICATION;IRON;SURVIVAL;TUBERCULOSIS
0
null
conjugation;iron utilization pathways;Mycobacteria;RecA;synthetic genetic array
15
CHROMOSOMAL DNA;conjugation;IDENTIFICATION;IRON;iron utilization pathways;Mycobacteria;RecA;SURVIVAL;synthetic genetic array;TUBERCULOSIS
WOS:000411075700009
New York State Dept Hlth, Albany, NY USA;SUNY Albany, Albany, NY USA
USA
2,017
null
0000-0002-4602-0205
null
null
English
null
BIOTECHNIQUES;CELL;CURR OPIN MICROBIOL;GENOME ANNOUNCEMENTS;J BACTERIOL;METHOD ENZYMOL;MOL BIOSYST;MOL MICROBIOL;NAT CHEM BIOL;NAT GENET;NAT METHODS;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS BIOL;PLOS GENET;PLOS PATHOG;RNA;SCIENCE;TUBERCULOSIS
Boucher, Nathalie;Derbyshire, Keith M;Gray, Todd A;Judd, Julius;Van Roey, Erik
2024-03-11 ER
Andries, K;Babu, M;Butland, G;Chowdhury, R P;Coros, A;Dussurget, O;Fang, Z;Fernandes, N D;Flint, J L;Gray, T A;Griffin, J E;Guo, X V;Jacobs, W R;Joshi, S M;Kalscheuer, R;Kieser, K J;Lehner, B;Li, S K;Liu, Y G;Nguyen, K T;Nichols, R J;Ojha, A;Parsons, L M;Rengarajan, J;Roguev, A;Sassetti, C M;Schuldiner, M;Shell, S S;Shiloh, M U;Siegrist, M S;Silhavy, T J;Tong, A H Y;Typas, A;Van Kessel, J C;Wang, J;Wells, R M;Zuker, M
FH3UO
Albany, NY USA;Albany, NY USA.
4
null
2
null
28,784,812
Boucher, Nathalie;Derbyshire, Keith M;Gray, Todd A;Judd, Julius;Van Roey, Erik
J BACTERIOL
Albany, NY USA
Tei, H;Uriu, K
10.1016/j.jtbi.2017.06.005
null
24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
1u2vs3458u1c2272m6e4s1y172p5l581f2n2f
Feedback loops interlocked at competitive binding sites amplify and facilitate genetic oscillations
Kanazawa Univ
null
Uriu, K (corresponding author), Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan.
null
Tei, Hajime;Uriu, Koichiro
Biology;Mathematical & Computational Biology
JSPS KAKENHI [26840085]; Grants-in-Aid for Scientific Research [26840085, 17H05762] Funding Source: KAKEN
WOS
Uriu, K
Kanazawa Univ, Ishikawa, Japan
428
amplify;and;at;binding;competitive;Facilitate;feedback;genetic;interlocked;loops;oscillations;sites
1
Uriu, Koichiro
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan
Article
Kanazawa Univ
LONDON
null
null
Kanazawa Univ
Grants-in-Aid for Scientific Research;JSPS KAKENHI
Uriu, K (corresponding author), Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan.
64
Tei, Hajime;Uriu, Koichiro
10
1
406,079,800,007
Grants-in-Aid for Scientific Research [26840085, 17H05762] Funding Source: KAKEN;JSPS KAKENHI [26840085]
Japan
JOURNAL OF THEORETICAL BIOLOGY
Japan
null
null
Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan
0022-5193
Tei, H;Uriu, K
SEP 7
tei@staff.kanazawa-u.ac.jp;uriu@staff.kanazawa-u.ac.jp
competitive binding sites;feedback loops;genetic oscillations
2
J
Life Sciences & Biomedicine - Other Topics;Mathematical & Computational Biology
activator;activator ROR;additional mechanisms;amplification;amplitude;binding sites;Bmal1;Bmal1 oscillations;Bmal1 promoter;Bmal1 regulation;C 2017 Elsevier Ltd;Circadian clock;competitive binding sites;contrast;dissociation constants;expression levels;fast activator;fast repressor;feedback loops;genetic oscillations;integration;key;key clock gene Bmal1;large time scale separation;MAMMALIAN CIRCADIAN CLOCK;mechanism;METABOLISM;MODEL;necessary;negative feedback loops;noncompetitive binding sites;noncompetitive sites;optimal ratio;oscillation;OSCILLATIONS;peak phase difference;Phase difference;positive;preference;present;previous experiments;previous study;principles;regulation;regulatory networks;relative time;relative time scales;REPRESSOR;repressor REV-ERB;results;REV-ERB;REV-ERB-ALPHA;rights reserved;ROBUST;robust oscillations;ROR;ROR peaks;same binding sites;slow activator;slow repressor;small;small phase difference;SYNCHRONIZATION;Synthetic Genetic Oscillators;time scales;TRANSCRIPTION;transcription patterns
Uriu, K
AMPLITUDE;Bmal1;Circadian clock;MAMMALIAN CIRCADIAN CLOCK;MECHANISM;METABOLISM;MODEL;Phase difference;PRINCIPLES;REV-ERB-ALPHA;ROBUST;SYNCHRONIZATION;Synthetic genetic oscillators;TRANSCRIPTION
56
[Uriu, Koichiro; Tei, Hajime] Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan.
We thank Gen Kurosawa and Andrew Oates for their helpful comments on the manuscript. This work was supported by JSPS KAKENHI [26840085] to K.U.
activator;activator ROR;additional mechanisms;amplification;amplitude;binding sites;Bmal1;Bmal1 oscillations;Bmal1 promoter;Bmal1 regulation;circadian clock;competitive binding sites;contrast;dissociation constants;expression levels;fast activator;fast repressor;feedback loops;genetic oscillations;integration;key;key clock gene Bmal1;large time scale separation;mammalian circadian clock;necessary;negative feedback loops;noncompetitive binding sites;noncompetitive sites;optimal ratio;oscillation;oscillations;peak phase difference;positive;preference;present;previous experiments;previous study;regulation;regulatory networks;relative time;relative time scales;repressor;repressor REV-ERB;results;REV-ERB;robust oscillations;ROR;ROR peaks;same binding sites;slow activator;slow repressor;small;small phase difference;synthetic genetic oscillators;time scales;transcription patterns
10.1016/j.bpj.2014.07.022;10.1016/j.bpj.2015.09.024;10.1016/j.cell.2010.12.019;10.1016/j.cell.2016.05.012;10.1016/j.celrep.2013.03.013;10.1016/j.cmet.2016.10.003;10.1016/j.jtbi.2008.04.011;10.1016/j.molcel.2015.10.024;10.1016/j.neuron.2004.07.018;10.1016/j.physa.2015.02.091;10.1016/S0092-8674(02)00825-5;10.1016/S0092-8674(03)00074-6;10.1016/S0092-8674(03)00346-5;10.1038/msb.2012.62;10.1038/nature07389;10.1038/nature07616;10.1038/nature11048;10.1038/ng1504;10.1038/nrm2530;10.1038/nrm2995;10.1038/nsmb.3324;10.1038/srep05782;10.1073/pnas.0904837106;10.1073/pnas.1132112100;10.1073/pnas.1603799113;10.1073/pnas.2036281100;10.1088/1478-3975/13/3/035005;10.1103/PhysRevE.80.011926;10.1103/PhysRevE.94.052413;10.1103/PhysRevLett.102.068105;10.1126/science.1156951;10.1126/science.1226339;10.1126/science.aab3021;10.1186/1471-2199-5-18;10.1186/1752-0509-4-66;10.1371/journal.pbio.1000595;10.1371/journal.pcbi.0020030;10.1371/journal.pcbi.0030068;10.1371/journal.pcbi.1002309;10.1371/journal.pcbi.1002787;10.1371/journal.pcbi.1005266;10.1371/journal.pone.0018663;10.1371/journal.pone.0046835;10.1371/journal.pone.0104761;10.1529/biophysj.104.058388;10.1529/biophysj.106.094086
Kanazawa Univ
Tei, H;Uriu, K
Uriu, K: Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan
Uriu, Koichiro
17H05762;26840085
48
null
Japan
Kanazawa Univ
Uriu, Koichiro
null
AMPLITUDE;MAMMALIAN CIRCADIAN CLOCK;MECHANISM;METABOLISM;MODEL;PRINCIPLES;REV-ERB-ALPHA;ROBUST;SYNCHRONIZATION;TRANSCRIPTION
Uriu, Koichiro; Tei, Hajime;
null
Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan
Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan
1095-8541
Bmal1;Circadian clock;Phase difference;synthetic genetic oscillator
null
1982;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
5
Kanazawa Univ, Grad Sch Nat Sci & Technol, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan
J. Theor. Biol.
Tei, Hajime
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
,;a;activates;activator;additional;advantageous;amplification;amplifying;amplitude;an;and;are;arises;as;at;between;binding;Bmal1;both;by;circadian;clock;compensate;compete;competitive;comprise;constants;contrast;conversely;demonstrated;depends;difference;disadvantage;dissociation;enhance;examples;experiments;expression;facilitate;fast;feedback;for;forming;from;further;gene;generate;genetic;here;in;indicate;integration;interlocked;is;key;large;larger;later;levels;likely;loops;mammalian;mathematical;mechanisms;modeling;more;moreover;necessary;negative;networks;noncompetitive;of;often;on;only;optimal;oscillation;oscillations;oscillators;our;patterns;peak;peaks;phase;positive;predict;preferable;preference;present;previous;promoter;ratio;regulated;regulation;regulatory;relative;repressor;results;REV-ERB;reveal;robust;ROR;same;scale;scales;secondly;separation;show;similar;sites;slow;small;study;synthetic;than;that;the;their;them;therefore;these;this;time;to;transcription;under;using;we;when;with
Kanazawa Univ
Positive and negative feedback loops are often present in regulatory networks for genetic oscillations. Relative time scales and integration of these feedback loops are key to robust oscillations in expression levels. Using examples from the circadian clock and synthetic genetic oscillators, we study positive and negative feedback loops interlocked at competitive binding sites. In the mammalian circadian clock, a key clock gene Bmal1 is regulated by the activator ROR and the repressor REV-ERB. Conversely, Bmal1 activates both of them, forming interlocked feedback loops. Previous experiments indicate that the activator and repressor compete for the same binding sites in the Bmal1 promoter. Transcription patterns predict that ROR peaks later than REV-ERB and, moreover, the peak phase difference between them is small. Using mathematical modeling we reveal an optimal ratio of dissociation constants of an activator and a repressor for the competitive binding sites to enhance the amplitude of Bmal1 oscillations. This optimal ratio arises only when the amplitude of the repressor is larger than that of the activator. Secondly, we reveal that the preference of binding sites for an activator and a repressor depends on their relative time scales. A previous study demonstrated that noncompetitive binding sites are preferable for synthetic genetic oscillators that comprise a fast activator and a slow repressor with a large time scale separation. Here we show that when their time scales are similar, competitive binding sites are more likely to generate oscillation than noncompetitive sites. In contrast, for a slow activator and a fast repressor with a small phase difference as in Bmal1 regulation, noncompetitive binding sites are advantageous for amplifying oscillations. Our results, therefore, predict that additional mechanisms are necessary to compensate the disadvantage of the Bmal1 promoter and further facilitate amplification under the regulation by ROR and REV-ERB.
L-3596-2015
AMPLITUDE;MAMMALIAN CIRCADIAN CLOCK;MECHANISM;METABOLISM;MODEL;PRINCIPLES;REV-ERB-ALPHA;ROBUST;SYNCHRONIZATION;TRANSCRIPTION
0
null
Bmal1;Circadian clock;Phase difference;Synthetic genetic oscillators
9
AMPLITUDE;Bmal1;Circadian clock;MAMMALIAN CIRCADIAN CLOCK;MECHANISM;METABOLISM;MODEL;Phase difference;PRINCIPLES;REV-ERB-ALPHA;ROBUST;SYNCHRONIZATION;synthetic genetic oscillator;TRANSCRIPTION
WOS:000406079800007
Kanazawa Univ, Ishikawa, Japan
Japan
2,017
null
0000-0003-1802-2470
null
null
English
null
BIOPHYS J;BMC MOL BIOL;BMC SYST BIOL;CELL;CELL METAB;CELL REP;J THEOR BIOL;Models of biological pattern formation;MOL CELL;MOL SYST BIOL;NAT GENET;NAT REV MOL CELL BIO;NAT STRUCT MOL BIOL;NATURE;NEURON;P NATL ACAD SCI USA;PAP PHYS;PHYS BIOL;PHYS REV E;PHYS REV LETT;PHYSICA A;PLOS BIOL;PLOS COMPUT BIOL;PLOS ONE;SCI REP-UK;SCIENCE
Tei, Hajime;Uriu, Koichiro
2024-03-11 ER
Ananthasubramaniam, B;Atkinson, M R;Bernard, S;Cho, H;Cyran, S A;Forger, D B;Gonze, D;Guantes, R;Huang, B;Jolley, C C;Kim, J K;Koike, N;Korencic, A;Leloup, J C;Lengyel I. M.;Li, Y;Marino, S;Mather, W;Meinhardt H.;Mirsky, H P;Monti, M;Munteanu, A;Narumi, R;Novák, B;Ogawa, Y;Papazyan, R;Pett, J P;Preitner, N;Relógio, A;Rey, G;Sato, T K;Stricker, J;Tian, X J;Tigges, M;To, T L;Tokuda, I T;Tsai, T Y C;Ueda, H R;Ukai-Tadenuma, M;Wang, J K;Webb, A B;Westermark, P O;Yamamoto, T;Zhang, E E;Zhang, Y X;Zhao, X;Zhu, B K
FB3YX
Ishikawa, Japan
6
null
1
null
28,625,476
Tei, Hajime;Uriu, Koichiro
J THEOR BIOL
Ishikawa, Japan
Aisyah;Alisjahbana, B;Damayanti, R R R;Handali, S;Ihsanawati;Natalia, D;Puspasari, F;Putri, R D;Yuwita, A
10.1016/j.apjtb.2017.07.017
null
WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S NO 1498A-2 VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA
2h5d2yk125e58394e254j1ie5t5h3a19xa6q
Construction and expression of a synthetic gene encoding nonstructural glycoprotein NS1 of dengue 2 virus in <i>Pichia</i> <i>pastoris</i>
Inst Technol Bandung
null
Natalia, D (corresponding author), Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia.
null
Aisyah;Alisjahbana, Bachti;Damayanti, Raden Roro Rika;Handali, Sukwan;Ihsanawati;Natalia, Dessy;Puspasari, Fernita;Putri, Riski Dwimalida;Yuwita, Anita
Tropical Medicine
Ministry of Research, Technology, and Higher Education of Indonesia [0400/I1/B04/SPK-WRRI/VI/2014]
WOS
Natalia, D
Inst Technol Bandung, Bandung, Indonesia;Padjadjaran State Univ, Jatinangor, Indonesia;Pakar Biomed Indonesia, Bandung, Indonesia
7
2;<i>pastoris</i>;<i>Pichia</i>;a;and;construction;dengue;encoding;expression;gene;glycoprotein;in;nonstructural;NS1;of;synthetic;virus
1
Puspasari, Fernita
WOLTERS KLUWER MEDKNOW PUBLICATIONS
Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia;Padjadjaran State Univ, Fac Med, Jl Raya Bandung Sumedang KM21, Jatinangor, Indonesia;Pakar Biomed Indonesia, Jl Rancabentang 12B, Bandung 40142, Indonesia
Article
Inst Technol Bandung
MUMBAI
null
null
Inst Technol Bandung;Padjadjaran State Univ;Pakar Biomed Indonesia
Ministry of Research, Technology, and Higher Education of Indonesia
Natalia, D (corresponding author), Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia.
693
Aisyah;Alisjahbana, Bachti;Damayanti, Raden Roro Rika;Handali, Sukwan;Ihsanawati;Natalia, Dessy;Puspasari, Fernita;Putri, Riski Dwimalida;Yuwita, Anita
3
3
408,640,800,004
Ministry of Research, Technology, and Higher Education of Indonesia [0400/I1/B04/SPK-WRRI/VI/2014]
Indonesia
ASIAN PACIFIC JOURNAL OF TROPICAL BIOMEDICINE
Indonesia
null
null
Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia
2221-1691
Aisyah;Alisjahbana, B;Damayanti, R R R;Handali, S;Ihsanawati;Natalia, D;Puspasari, F;Putri, R D;Yuwita, A
AUG
dessy@chem.itb.ac.id
<i>Pichia</i> <i>pastoris</i>;dengue 2 virus;expression;synthetic gene encoding nonstructural glycoprotein NS1
9
J
Tropical Medicine
2% (v/v) methanol;45 kDa;72 h;<i>Pichia</i> <i>pastoris</i>;antigenicity;codon;commercial rapid test;conclusions;dengue 2 virus;dengue diagnostic kit;DENV-2 NS1 amino acid sequences;development;expression;expression vector;Indonesian-specific DENV2 virus;induction;methods;molecular weight;monoclonal antibody;Ni-NTA affinity chromatography;NS1;optimal expression condition;P. pastoris KM71;P. pastoris pPICZ alpha;pastoris);Pichia pastoris (P;potential candidate;PROTEIN;purified recombinant DENV-2 NS1 protein;recombinant DENV-2 NS1 protein;resulting recombinant DENV-2 NS1 protein;results;synthetic gene;synthetic gene encoding nonstructural glycoprotein NS1;tested;use;vaccine
Puspasari, F
null
689
[Puspasari, Fernita; Putri, Riski Dwimalida; Aisyah; Damayanti, Raden Roro Rika; Ihsanawati; Natalia, Dessy] Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia. [Yuwita, Anita; Handali, Sukwan] Pakar Biomed Indonesia, Jl Rancabentang 12B, Bandung 40142, Indonesia. [Alisjahbana, Bachti] Padjadjaran State Univ, Fac Med, Jl Raya Bandung Sumedang KM21, Jatinangor, Indonesia.
We thank "Penelitian Unggulan Strategis Nasional 2013" under the contract number of 0400/I1/B04/SPK-WRRI/VI/2014, Ministry of Research, Technology, and Higher Education of Indonesia, for funding this work.
2% (v/v) methanol;45 kDa;72 h;antigenicity;codon;commercial rapid test;conclusions;dengue diagnostic kit;DENV-2 NS1 amino acid sequences;development;expression vector;Indonesian-specific DENV2 virus;induction;methods;molecular weight;monoclonal antibody;Ni-NTA affinity chromatography;NS1;optimal expression condition;P. pastoris KM71;P. pastoris pPICZ alpha;pastoris);Pichia pastoris (P;potential candidate;protein;purified recombinant DENV-2 NS1 protein;recombinant DENV-2 NS1 protein;resulting recombinant DENV-2 NS1 protein;results;synthetic gene;tested;use;vaccine
10.1007/s00253-014-5963-5;10.1007/s11262-005-0036-6;10.1007/s11262-012-0851-5;10.1016/j.antiviral.2009.11.009;10.1016/j.antiviral.2013.03.008;10.1016/j.antiviral.2013.09.013;10.1016/j.jviromet.2010.04.003;10.1016/j.pep.2009.02.003;10.1093/nar/15.3.1281;10.1155/2013/343195;10.1371/journal.pone.0080891;10.1385/MB:16:1:23;10.2144/04361DD02
Inst Technol Bandung
Aisyah;Alisjahbana, B;Damayanti, R R R;Handali, S;Ihsanawati;Natalia, D;Puspasari, F;Putri, R D;Yuwita, A
Puspasari, F: Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia
null
0400/I1/B04/SPK-WRRI/VI/2014
13
null
Indonesia
Inst Technol Bandung;Padjadjaran State Univ;Pakar Biomed Indonesia
Puspasari, Fernita
gold
null
Puspasari, Fernita; Putri, Riski Dwimalida; Aisyah; Damayanti, Raden Roro Rika; Yuwita, Anita; Alisjahbana, Bachti; Handali, Sukwan; Ihsanawati; Natalia, Dessy;
null
Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia;Padjadjaran State Univ, Fac Med, Jl Raya Bandung Sumedang KM21, Jatinangor, Indonesia;Pakar Biomed Indonesia, Jl Rancabentang 12B, Bandung 40142, Indonesia
Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia;Padjadjaran State Univ, Fac Med, Jl Raya Bandung Sumedang KM21, Jatinangor, Indonesia;Pakar Biomed Indonesia, Jl Rancabentang 12B, Bandung 40142, Indonesia
2588-9222
null
8
1987;2000;2004;2006;2009;2010;2013;2015
2
Inst Technol Bandung, Fac Math & Nat Sci, Biochem Res Div, Jl Ganesha 10, Bandung 40132, Indonesia
Asian Pac. Trop. Biomed.
Natalia, Dessy
WOLTERS KLUWER MEDKNOW PUBLICATIONS
(p;(v/v);,;2%;45;72;:;a;able;achieved;acid;affinity;alpha;amino;and;antibody;antigenicity;as;by;candidate;characterize;chromatography;codon;commercial;commercially;conclusions;condition;dengue;DENV-2;DENV2;derived;development;diagnostic;express;expression;for;from;gene;h;in;Indonesian-specific;induction;inserted;interact;into;is;its;kDa;kit;KM71;methanol;methods;molecular;monoclonal;Ni-NTA;NS1;objectives;of;optimal;optimized;P.;pastoris;pastoris);Pichia;potential;pPICZ;produced;protein;purified;rapid;recombinant;resulting;results;secreted;sequences;similar;synthesized;synthetic;test;tested;the;to;use;vaccine;vector;virus;was;weight;with
Inst Technol Bandung
Objectives: To express and characterize NS1 of Indonesian-specific DENV2 virus in Pichia pastoris (P. pastoris). Methods: A codon optimized synthetic gene derived from the DENV-2 NS1 amino acid sequences was synthesized commercially and inserted into the P. pastoris pPICZ alpha A expression vector. The recombinant DENV-2 NS1 protein was purified by Ni-NTA affinity chromatography, and its antigenicity was tested. Results: The recombinant DENV-2 NS1 protein was secreted as a protein with a molecular weight of similar to 45 kDa, and the optimal expression condition was achieved by induction with 2% (v/v) methanol for 72 h. The purified recombinant DENV-2 NS1 protein was able to interact with a monoclonal antibody of NS1 in a commercial rapid test. Conclusions: The resulting recombinant DENV-2 NS1 protein produced in P. pastoris KM71 is a potential candidate for use in the development of a dengue diagnostic kit and vaccine.
null
null
0
null
null
5
null
WOS:000408640800004
Inst Technol Bandung, Bandung, Indonesia;Padjadjaran State Univ, Jatinangor, Indonesia;Pakar Biomed Indonesia, Bandung, Indonesia
Indonesia
2,017
null
0000-0002-8953-8805
null
null
English
null
ANTIVIR RES;APPL MICROBIOL BIOT;BIOMED RES INT;BIOTECHNIQUES;J VIROL METHODS;MOL BIOTECHNOL;NUCLEIC ACIDS RES;PLOS ONE;PROTEIN EXPRES PURIF;VIRUS GENES
Aisyah;Alisjahbana, Bachti;Damayanti, Raden Roro Rika;Handali, Sukwan;Ihsanawati;Natalia, Dessy;Puspasari, Fernita;Putri, Riski Dwimalida;Yuwita, Anita
2024-03-11 ER
Amorim, J H;Athmaram, T N;Bollati, M;Bragança, C R S;Cregg, J M;Das, D;Kosasih, H;Lim, S P;Muller, D A;Sankar, S G;Sharp, P M;Wu, S X;Zhou, J M
FF1DU
Bandung, Indonesia
2
null
3
null
null
Aisyah;Alisjahbana, Bachti;Damayanti, Raden Roro Rika;Handali, Sukwan;Ihsanawati;Natalia, Dessy;Puspasari, Fernita;Putri, Riski Dwimalida;Yuwita, Anita
ASIAN PAC J TROP BIO
Bandung, Indonesia;Jatinangor, Indonesia
Beck, J L;Collins, J J;Del Vecchio, D;Dy, A J;Martin, K B;Murray, R M;Ng, A H;Yeung, E
10.1016/j.cels.2017.06.001
null
50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
3z81y1j3b2k2w684r4j2r2z6k1nl5u6nz5q31
Biophysical Constraints Arising from Compositional Context in Synthetic Gene Networks
Pacific Northwest Natl Lab
null
Yeung, E (corresponding author), Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA.
null
Beck, James L;Collins, James J;Del Vecchio, Domitilla;Dy, Aaron J;Martin, Kyle B;Murray, Richard M;Ng, Andrew H;Yeung, Enoch
Biochemistry & Molecular Biology;Cell Biology
Charles Lee Powell Foundation Fellowship; Kanel Foundation Fellowship; National Science Foundation Graduate Fellowship; National Defense Science and Engineering Graduate Fellowship; Air Force Office of Scientific Research grant (AFOSR) [FA9550-14-1-0060]; Defense Threat Reduction Agency [HDTRA1-14-1-0006]; Defense Advanced Research Projects Agency [HR0011-12-C-0065]; Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [1317694] Funding Source: National Science Foundation
WOS
Yeung, E
Broad Inst MIT & Harvard, Cambridge, MA USA;CALTECH, Pasadena, CA USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Cambridge, MA USA;MIT, Cambridge, MA USA;Pacific Northwest Natl Lab, Richland, WA USA;Univ Calif Berkeley, Berkeley, CA USA
5
Arising;biophysical;Compositional;Constraints;Context;From;gene;in;networks;synthetic
1
null
CELL PRESS
Broad Inst MIT & Harvard, Cambridge, MA USA;CALTECH, Dept Civil & Mech Engn, Pasadena, CA 91125 USA;CALTECH, Dept Comp & Math Sci, Control & Dynam Syst, Pasadena, CA 91125 USA;CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA;MIT, Inst Med Engn & Sci, Synthet Biol Ctr, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA;Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
Article
Pacific Northwest Natl Lab
CAMBRIDGE
null
null
Broad Inst MIT & Harvard;CALTECH;Harvard MIT Program Hlth Sci & Technol;Harvard Univ;MIT;Pacific Northwest Natl Lab;Univ Calif Berkeley
Air Force Office of Scientific Research grant (AFOSR);Charles Lee Powell Foundation Fellowship;Defense Advanced Research Projects Agency;Defense Threat Reduction Agency;Direct For Computer & Info Scie & Enginr;Division of Computing and Communication Foundations;Kanel Foundation Fellowship;National Defense Science and Engineering Graduate Fellowship;National Science Foundation Graduate Fellowship
Yeung, E (corresponding author), Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA.
+
Beck, James L;Collins, James J;Del Vecchio, Domitilla;Dy, Aaron J;Martin, Kyle B;Murray, Richard M;Ng, Andrew H;Yeung, Enoch
12
10
406,295,900,003
Air Force Office of Scientific Research grant (AFOSR) [FA9550-14-1-0060];Charles Lee Powell Foundation Fellowship;Defense Advanced Research Projects Agency [HR0011-12-C-0065];Defense Threat Reduction Agency [HDTRA1-14-1-0006];Direct For Computer & Info Scie & Enginr;Division of Computing and Communication Foundations [1317694] Funding Source: National Science Foundation;Kanel Foundation Fellowship;National Defense Science and Engineering Graduate Fellowship;National Science Foundation Graduate Fellowship
USA
CELL SYSTEMS
USA
null
null
Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA
2405-4712
Beck, J L;Collins, J J;Del Vecchio, D;Dy, A J;Martin, K B;Murray, R M;Ng, A H;Yeung, E
JUL 26
enoch.yeung@pnnl.gov
biophysical Constraints;Compositional Context;synthetic gene networks
8
J
Biochemistry & Molecular Biology;Cell Biology
30%;400% higher expression;biophysical Constraints;cells;coding sequences;Compositional Context;convergent genes;divergent-;DNA TOPOLOGY;DNA);dynamic range;Effects;ELEMENTS;entire genes;ESCHERICHIA-COLI;expression;expression levels;FLUORESCENT PROTEIN;gene expression;genes;greater ultrasensitivity;gyrase;hypothesis;ILVYC OPERON;induced;induced genes;induction;intergenic compositional context (spatial arrangement;intergenic context effects;intragenic compositional context (promoter structure;modeling;one;orientation;PROMOTER;promoters;ribosome binding sites);RNA;spacing regions;supercoiling;supercoiling effects;switch stability;Synthetic gene expression;synthetic gene networks;taking advantage;tandem genes;tandem orientations;tandem- oriented genes;threshold detection;toggle switch;TRANSCRIPTION;transcriptional interference;treatment;vitro supercoiling relaxation experiments
Yeung, E
CELLS;DNA TOPOLOGY;ELEMENTS;ESCHERICHIA-COLI;EXPRESSION;FLUORESCENT PROTEIN;ILVYC OPERON;PROMOTERS;RNA;TRANSCRIPTION
11
[Yeung, Enoch] Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA. [Murray, Richard M.] CALTECH, Dept Comp & Math Sci, Control & Dynam Syst, Pasadena, CA 91125 USA. [Dy, Aaron J.; Collins, James J.] MIT, Inst Med Engn & Sci, Synthet Biol Ctr, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Martin, Kyle B.; Murray, Richard M.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Ng, Andrew H.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. [Del Vecchio, Domitilla] MIT, Synthet Biol Ctr, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Beck, James L.] CALTECH, Dept Civil & Mech Engn, Pasadena, CA 91125 USA. [Collins, James J.] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA. [Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. [Dy, Aaron J.; Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA USA.
We thank Ophelia Venturelli for her invaluable inspiration and guidance in this project; Victoria Hsiao, Jin Park, Anu Thubagere, and Adam Rosenthal for great advice on imaging; David Younger, Ania Baetica, Vincent Noireaux, Clarmyra Hayes, and Zachary Z. Sun for guidance and assistance with TX-TL experiments; and Lea Goentoro, Johann Pauls-son, Long Cai, Jennifer Brophy, John Doyle, Eric Klavins, and Julius Lucks for insightful conversations. This work was supported in part by a Charles Lee Powell Foundation Fellowship, a Kanel Foundation Fellowship, a National Science Foundation Graduate Fellowship, a National Defense Science and Engineering Graduate Fellowship, Air Force Office of Scientific Research grant (AFOSR) FA9550-14-1-0060, Defense Threat Reduction Agency grant HDTRA1-14-1-0006, and Defense Advanced Research Projects Agency grant HR0011-12-C-0065.
30%;400% higher expression;coding sequences;convergent genes;divergent-;DNA);dynamic range;effects;entire genes;expression;expression levels;gene expression;genes;greater ultrasensitivity;gyrase;hypothesis;induced;induced genes;induction;intergenic compositional context (spatial arrangement;intergenic context effects;intragenic compositional context (promoter structure;modeling;one;orientation;promoter;ribosome binding sites);spacing regions;supercoiling;supercoiling effects;switch stability;synthetic gene expression;synthetic gene networks;taking advantage;tandem genes;tandem orientations;tandem- oriented genes;threshold detection;toggle switch;transcriptional interference;treatment;vitro supercoiling relaxation experiments
10.1002/biot.201200085;10.1016/0022-2836(92)90721-U;10.1016/0092-8674(85)90112-6;10.1016/j.bpj.2015.06.034;10.1016/j.cell.2008.01.027;10.1016/j.cell.2014.05.038;10.1016/j.chembiol.2015.04.018;10.1016/j.gde.2005.02.007;10.1016/j.tig.2005.04.009;10.1021/bi00332a018;10.1021/ja037994o;10.1021/ja411060p;10.1021/sb200016s;10.1021/sb400203p;10.1038/35002131;10.1038/msb.2011.38;10.1038/nature11516;10.1038/nbt988;10.1038/nprot.2011.432;10.1038/nrm976;10.1046/j.1365-2958.2001.02249.x;10.1073/pnas.0402940101;10.1073/pnas.1301301110;10.1073/pnas.2135496100;10.1073/pnas.84.20.7024;10.1073/pnas.96.25.14294;10.1088/1478-3975/4/4/001;10.1093/nar/25.6.1203;10.1093/nar/gkq810;10.1093/nar/gks014;10.1109/CDC.2013.6760079;10.1111/j.1365-2958.2005.05006.x;10.1126/science.1207339;10.1128/AEM.70.11.6809-6815.2004;10.1128/jb.169.10.4499-4506.1987;10.1146/annurev.genet.36.032902.111815;10.1186/1754-1611-5-12;10.1371/journal.pcbi.1003785;10.1371/journal.pone.0003647;10.15252/msb.20156540;[10.1038/NMETH.1318, 10.1038/nmeth.1318];[10.1038/nmeth.2403, 10.1038/NMETH.2403];[10.1038/NMETH.2404, 10.1038/nmeth.2404];[10.1038/NMETH.3339, 10.1038/nmeth.3339]
Pacific Northwest Natl Lab
Beck, J L;Collins, J J;Del Vecchio, D;Dy, A J;Martin, K B;Murray, R M;Ng, A H;Yeung, E
Yeung, E: Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA
Dy, Aaron J
1317694;FA9550-14-1-0060;HDTRA1-14-1-0006;HR0011-12-C-0065
47
null
USA
Broad Inst MIT & Harvard;CALTECH;Harvard MIT Program Hlth Sci & Technol;Harvard Univ;MIT;Pacific Northwest Natl Lab;Univ Calif Berkeley
Yeung, Enoch
Green Submitted, Bronze
CELLS;DNA TOPOLOGY;ELEMENTS;ESCHERICHIA-COLI;EXPRESSION;FLUORESCENT PROTEIN;ILVYC OPERON;PROMOTERS;RNA;TRANSCRIPTION
Yeung, Enoch; Dy, Aaron J.; Martin, Kyle B.; Ng, Andrew H.; Del Vecchio, Domitilla; Beck, James L.; Collins, James J.; Murray, Richard M.;
null
Broad Inst MIT & Harvard, Cambridge, MA USA;CALTECH, Dept Civil & Mech Engn, Pasadena, CA 91125 USA;CALTECH, Dept Comp & Math Sci, Control & Dynam Syst, Pasadena, CA 91125 USA;CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA;MIT, Inst Med Engn & Sci, Synthet Biol Ctr, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA;Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
Broad Inst MIT & Harvard, Cambridge, MA USA;CALTECH, Dept Civil & Mech Engn, Pasadena, CA 91125 USA;CALTECH, Dept Comp & Math Sci, Control & Dynam Syst, Pasadena, CA 91125 USA;CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA;MIT, Inst Med Engn & Sci, Synthet Biol Ctr, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA;Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
2405-4720
null
1
1985;1987;1992;1997;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2011;2012;2013;2014;2015;2016
68
Pacific Northwest Natl Lab, Computat & Stat Analyt Div, Data Sci & Analyt Grp, Richland, WA 99352 USA
Cell Syst.
Murray, Richard M
CELL PRESS
(promoter;(spatial;,;30%;400%;about;abrogated;advantage;affects;and;are;arranged;arrangement;between;binding;both;bringing;by;can;coding;compare;compositional;context;convergent;detection;differences;divergent;divergent-;DNA);dynamic;each;effects;entire;experiments;explain;expression;gene;genes;greater;gyrase;higher;highly;however;hypothesis;improve;in;induced;induction;interference;intergenic;intragenic;is;known;less;levels;mediated;modeling;much;networks;of;on;one;or;orientation;orientations;oriented;other;postulate;promoter;range;rebuilt;regions;relaxation;Ribosome;sensitive;sequences;sites);spacing;stability;structure;supercoiling;switch;synthetic;taking;tandem;tandem-;than;that;the;this;threshold;through;to;toggle;transcriptional;treatment;ultrasensitivity;up;validate;vitro;we;whether;with;within;yielded
Pacific Northwest Natl Lab
Synthetic gene expression is highly sensitive to intragenic compositional context (promoter structure, spacing regions between promoter and coding sequences, and ribosome binding sites). However, much less is known about the effects of intergenic compositional context (spatial arrangement and orientation of entire genes on DNA) on expression levels in synthetic gene networks. We compare expression of induced genes arranged in convergent, divergent, or tandem orientations. Induction of convergent genes yielded up to 400% higher expression, greater ultrasensitivity, and dynamic range than divergent- or tandem- oriented genes. Orientation affects gene expression whether one or both genes are induced. We postulate that transcriptional interference in divergent and tandem genes, mediated by supercoiling, can explain differences in expression and validate this hypothesis through modeling and in vitro supercoiling relaxation experiments. Treatment with gyrase abrogated intergenic context effects, bringing expression levels within 30% of each other. We rebuilt the toggle switch with convergent genes, taking advantage of supercoiling effects to improve threshold detection and switch stability.
H-7052-2016
CELLS;DNA TOPOLOGY;ELEMENTS;ESCHERICHIA-COLI;EXPRESSION;FLUORESCENT PROTEIN;ILVYC OPERON;PROMOTER;RNA;TRANSCRIPTION
0
null
null
26
ESCHERICHIA-COLI;CELLS;DNA TOPOLOGY;ELEMENTS;EXPRESSION;FLUORESCENT PROTEIN;ILVYC OPERON;PROMOTER;RNA;TRANSCRIPTION
WOS:000406295900003
Broad Inst MIT & Harvard, Cambridge, MA USA;CALTECH, Pasadena, CA USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Cambridge, MA USA;MIT, Cambridge, MA USA;Pacific Northwest Natl Lab, Richland, WA USA;Univ Calif Berkeley, Berkeley, CA USA
USA
2,017
null
null
null
null
English
null
ACS SYNTH BIOL;ANNU REV GENET;APPL ENVIRON MICROB;BIOCHEMISTRY-US;BIOPHYS J;BIOTECHNOL J;CELL;CHEM BIOL;CURR OPIN GENET DEV;ECOSAL PLUS;IEEE DECIS CONTR P;J AM CHEM SOC;J BACTERIOL;J Biol Eng;J BIOL METHODS;J MOL BIOL;MOL MICROBIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT METHODS;NAT PROTOC;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS BIOL;PLOS COMPUT BIOL;PLOS ONE;SCIENCE;TRENDS GENET
Beck, James L;Collins, James J;Del Vecchio, Domitilla;Dy, Aaron J;Martin, Kyle B;Murray, Richard M;Ng, Andrew H;Yeung, Enoch
2024-03-11 ER
[Anonymous];Babendure, J R;Balke, V L;Berg J.M.;Bintu, L;Brophy, J A N;Buc, H;Cardinale, S;Ceroni, F;Chong, S S;Davis, J H;Drolet, M;Edelstein A. D.;Engler, C;Filonov, G S;Gardner, T S;Gibson, D G;Gyorgy, A;Han, K Y;Hatfield, G W;Kalisky, T;Kobayashi, H;Korbel, J O;Kosuri, S;Larson, M H;Lee, T S;Liu, L F;Lutz, R;Maier, T;Meyer, S;Moon, T S;Mutalik, V K;Nelson, H C M;Noireaux, V;Opel, M L;Ouafa, Z A;Paige, J S;Rahmouni, A R;Rhee, K Y;Shearwin, K E;Shin, J;Siegal-Gaskins, D;Tuza, Z A;Veening, J W;Young, J W;Zhang, J
FB7BK
Richland, WA USA
81
null
7
null
28,734,826
Beck, James L;Collins, James J;Del Vecchio, Domitilla;Dy, Aaron J;Martin, Kyle B;Murray, Richard M;Ng, Andrew H;Yeung, Enoch
CELL SYST
Berkeley, CA USA;Cambridge, MA USA;Pasadena, CA USA;Richland, WA USA
Ding, Y F;Fan, J Z;Li, B Q;Li, J N;Pan, T R;Tan, C M;Tseng, K H;Villarreal, F;Weyers, B
10.1039/c7lc00382j
null
THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND
253k4d2f5l2k4q1r3w6x5743v39212f2p125x1u
Multi-dimensional studies of synthetic genetic promoters enabled by microfluidic impact printing
Univ Calif Davis
null
Li, BQ (corresponding author), Univ Sci & Technol China, Dept Precis Machinery Precis Instrumentat, Hefei 230027, Anhui, Peoples R China.;Li, BQ; Tan, CM; Pan, TR (corresponding author), Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA.
null
Ding, Yunfeng;Fan, Jinzhen;Li, Baoqing;Li, Jiannan;Pan, Tingrui;Tan, Cheemeng;Tseng, Kuo Hao;Villarreal, Fernando;Weyers, Brent
Biochemical Research Methods;Chemistry, Analytical;Chemistry, Multidisciplinary;Instruments & Instrumentation;Nanoscience & Nanotechnology
National Science Foundation [ECCS-0846502, DBI-1256193]; National Institute of Environmental Health Sciences of the NIH Superfund Research Program [P42ES004699]; National Natural Science Foundation of China [51675505]; Branco Weiss Fellowship
WOS
Li, B Q;Pan, T R;Tan, C M
Univ Calif Davis, Davis, CA USA;Univ Sci & Technol China, Anhui, Peoples R China
17
by;enabled;genetic;impact;Microfluidic;multi-dimensional;of;printing;promoters;studies;synthetic
2
Fan, Jinzhen;Li, Jiannan;Tan, Cheemeng;Villarreal, Fernando;Weyers, Brent William
ROYAL SOC CHEMISTRY
CM; Pan, TR (corresponding author), Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA.; Li, BQ (corresponding author), Univ Sci & Technol China, Dept Precis Machinery Precis Instrumentat, Hefei 230027, Anhui, Peoples R China;Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA;Univ Sci & Technol China, Dept Precis Machinery Precis Instrumentat, Hefei 230027, Anhui, Peoples R China
Article
Univ Calif Davis;Univ Sci & Technol China
CAMBRIDGE
null
null
Univ Calif Davis;Univ Sci & Technol China
Branco Weiss Fellowship;National Institute of Environmental Health Sciences of the NIH Superfund Research Program;National Natural Science Foundation of China;National Science Foundation
Li, BQ; Tan, CM; Pan, TR (corresponding author), Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA.; Li, BQ (corresponding author), Univ Sci & Technol China, Dept Precis Machinery Precis Instrumentat, Hefei 230027, Anhui, Peoples R China.
2207
Ding, Yunfeng;Fan, Jinzhen;Li, Baoqing;Li, Jiannan;Pan, Tingrui;Tan, Cheemeng;Tseng, Kuo Hao;Villarreal, Fernando;Weyers, Brent
41
2
404,469,800,005
Branco Weiss Fellowship;National Institute of Environmental Health Sciences of the NIH Superfund Research Program [P42ES004699];National Natural Science Foundation of China [51675505];National Science Foundation [ECCS-0846502, DBI-1256193]
China;USA
LAB ON A CHIP
China;USA.;
null
null
Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA
1473-0197
Ding, Y F;Fan, J Z;Li, B Q;Li, J N;Pan, T R;Tan, C M;Tseng, K H;Villarreal, F;Weyers, B
JUL 7
bqli@ustc.edu.cn;cmtan@ucdavis.edu;tingrui@ucdavis.edu
microfluidic impact printing;multi-dimensional studies;synthetic genetic promoters
9
J
Biochemistry & Molecular Biology;Chemistry;Instruments & Instrumentation;Science & Technology - Other Topics
1 mu L drop;1-10000-fold;100 pL-10 nL;ability;accurate direct dilutions;BIOLOGY;cell;cell-free systems;CHIP;combinatorial interactions;concentration;dilution;dose response;droplet printing;droplets;drug discovery;experimental combinations;experiments;factor;FREE PROTEIN EXPRESSION;gene regulatory modules;GENERATION;genetic promoters;GRADIENT;gradient printing system;impact printing;interactions;intractable number;limitation;major limitation;mathematical model;microfluidic impact printing;multi-dimensional data;multi-dimensional studies;multi-parametric;multifactorial design;multiple cis;multiple regulatory factors;natural genetic promoters;new frontier;parallel piezoelectric cantilever beams;platform;promoters;quantitative studies;range;scalable actuator array;SERIAL;single factor;synthetic;synthetic genetic promoter;synthetic genetic promoters;three regulatory factors;trans regulatory factors;transfer function;tunable volumes;use
Fan, J Z
BIOLOGY;CELL;CHIP;DILUTION;DRUG DISCOVERY;FREE PROTEIN EXPRESSION;GENERATION;GRADIENT;PLATFORM;SERIAL
2198
[Fan, Jinzhen; Villarreal, Fernando; Weyers, Brent; Ding, Yunfeng; Tseng, Kuo Hao; Li, Jiannan; Li, Baoqing; Tan, Cheemeng; Pan, Tingrui] Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA. [Li, Baoqing] Univ Sci & Technol China, Dept Precis Machinery Precis Instrumentat, Hefei 230027, Anhui, Peoples R China.
This research work has been supported in part by the National Science Foundation Awards ECCS-0846502 and DBI-1256193 to TP. JF acknowledges traineeship support from the National Institute of Environmental Health Sciences of the NIH Superfund Research Program (No. P42ES004699). BL acknowledges grant support from the National Natural Science Foundation of China (No. 51675505). CT acknowledges grant support from the Branco Weiss Fellowship. The authors would like to acknowledge Ray Lin for his assistance in software programming and circuit board design and Samantha Kennedy for her assistance in mechanical printer-head designs.
1 mu L drop;1-10000-fold;100 pL-10 nL;ability;accurate direct dilutions;cell-free systems;combinatorial interactions;concentration;dose response;droplet printing;droplets;experimental combinations;experiments;factor;gene regulatory modules;genetic promoters;gradient printing system;impact printing;interactions;intractable number;limitation;major limitation;mathematical model;multi-dimensional data;multi-dimensional studies;multi-parametric;multifactorial design;multiple cis;multiple regulatory factors;natural genetic promoters;new frontier;parallel piezoelectric cantilever beams;promoters;quantitative studies;range;scalable actuator array;single factor;synthetic;synthetic genetic promoter;three regulatory factors;trans regulatory factors;transfer function;tunable volumes;use
10.1002/cbic.200400321;10.1007/s10544-009-9385-6;10.1007/s11705-017-1610-x;10.1016/j.cell.2009.02.007;10.1016/j.copbio.2012.02.002;10.1016/j.ymben.2011.09.002;10.1016/S0006-3495(97)78307-3;10.1016/S0168-1605(02)00022-3;10.1016/S1359-6446(99)01388-4;10.1021/ac035114i;10.1021/ac2029198;10.1021/acssynbio.5b00296;10.1021/bp070133p;10.1021/ja037166v;10.1021/la000600b;10.1038/nature10315;10.1038/nchembio.218;10.1038/nrd1985;10.1039/b715524g;10.1039/b806140h;10.1039/b813582g;10.1039/c2ib00102k;10.1039/c5lc00432b;10.1039/c6lc00265j;10.1039/c6lc00636a;10.1039/c6ra08472a;10.1063/1.3580756;10.1063/1.4847815;10.1063/1.4928298;10.1073/pnas.0306752101;10.1073/pnas.1106752109;10.1088/1478-3975/2/3/P01;10.1093/nar/gkt052;10.1098/rsif.2009.0083.focus;10.1109/TCAD.2012.2202396;10.1109/TCAD.2013.2263035;10.1111/j.1556-4029.2010.01460.x;10.1128/JB.00994-09;10.1128/JCM.00932-16;10.1177/2211068211435302;10.2116/analsci.10.881
Univ Calif Davis
Ding, Y F;Fan, J Z;Li, B Q;Li, J N;Pan, T R;Tan, C M;Tseng, K H;Villarreal, F;Weyers, B
Fan, J Z: Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA
ding, yun;Li, baoqing;Weyers, Brent William
51675505;DBI-1256193;ECCS-0846502;P42ES004699
43
null
USA
Univ Calif Davis;Univ Sci & Technol China
Fan, Jinzhen
Green Accepted
BIOLOGY;CELL;CHIP;DILUTION;DRUG DISCOVERY;FREE PROTEIN EXPRESSION;GENERATION;GRADIENT;PLATFORM;SERIAL
Fan, Jinzhen; Villarreal, Fernando; Weyers, Brent; Ding, Yunfeng; Tseng, Kuo Hao; Li, Jiannan; Li, Baoqing; Tan, Cheemeng; Pan, Tingrui;
null
Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA;Univ Sci & Technol China, Dept Precis Machinery Precis Instrumentat, Hefei 230027, Anhui, Peoples R China
Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA;Univ Sci & Technol China, Dept Precis Machinery Precis Instrumentat, Hefei 230027, Anhui, Peoples R China
1473-0189
null
13
1994;1997;1999;2000;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2015;2016;2017
17
Univ Calif Davis, Dept Biomech Engn, Davis, CA 95616 USA;Univ Sci & Technol China, Dept Precis Machinery Precis Instrumentat, Hefei 230027, Anhui, Peoples R China
Lab Chip
Pan, Tingrui
ROYAL SOC CHEMISTRY
,;1;1-10000-fold;100;a;ability;accurate;actuator;and;apply;are;arise;array;as;at;beams;between;by;cantilever;cell-free;cis;combinations;combinatorial;comprises;concentration;constructs;creates;data;design;dilutions;direct;dose;drop;droplet;droplets;due;enable;established;experimental;experiments;facilitates;factor;factors;finally;first;for;from;frontier;function;gene;generate;genetic;gradient;has;highly;impact;in;integrate;interactions;intractable;is;L;limitation;limited;major;mathematical;model;modules;mu;multi-dimensional;multi-parametric;multifactorial;multiple;natural;new;next;nL;number;obtain;of;only;or;our;overcome;parallel;piezoelectric;pL-10;present;primarily;printing;promoter;promoters;quantitative;range;regulated;regulatory;respect;response;scalable;single;studies;study;such;synthetic;system;systems;technology;that;the;these;this;three;to;trans;transfer;tunable;typically;understand;use;using;varied;volumes;we;which;with;work
Univ Calif Davis;Univ Sci & Technol China
Natural genetic promoters are regulated by multiple cis and trans regulatory factors. For quantitative studies of these promoters, the concentration of only a single factor is typically varied to obtain the dose response or transfer function of the promoters with respect to the factor. Such design of experiments has limited our ability to understand quantitative, combinatorial interactions between multiple regulatory factors at promoters. This limitation is primarily due to the intractable number of experimental combinations that arise from multifactorial design of experiments. To overcome this major limitation, we integrate impact printing and cell-free systems to enable multi-dimensional studies of genetic promoters. We first present a gradient printing system which comprises parallel piezoelectric cantilever beams as a scalable actuator array to generate droplets with tunable volumes in the range of 100 pL-10 nL, which facilitates highly accurate direct dilutions in the range of 1-10000-fold in a 1 mu L drop. Next, we apply this technology to study interactions between three regulatory factors at a synthetic genetic promoter. Finally, a mathematical model of gene regulatory modules is established using the multi-parametric and multi-dimensional data. Our work creates a new frontier in the use of cell-free systems and droplet printing for multi-dimensional studies of synthetic genetic constructs.
ABE-8742-2021;GVR-9616-2022;HSB-4834-2023
BIOLOGY;CELLS;CHIP;DILUTION;DRUG DISCOVERY;FREE PROTEIN EXPRESSION;GENERATION;GRADIENTS;PLATFORM;SERIAL
0
null
null
10
BIOLOGY;CELLS;CHIP;DILUTION;DRUG DISCOVERY;FREE PROTEIN EXPRESSION;GENERATION;GRADIENTS;PLATFORM;SERIAL
WOS:000404469800005
Univ Calif Davis, Davis, CA USA;Univ Sci & Technol China, Anhui, Peoples R China
China;USA
2,017
null
0000-0002-1939-3401;0000-0002-4034-1243;0000-0002-6089-4785;0000-0002-7280-533X;0000-0003-1049-1192
null
null
English
null
ACS SYNTH BIOL;ANAL CHEM;ANAL SCI;BIOMED MICRODEVICES;BIOMICROFLUIDICS;BIOPHYS J;BIOTECHNOL PROGR;CELL;CHEMBIOCHEM;CURR OPIN BIOTECH;DRUG DISCOV TODAY;FRONT CHEM SCI ENG;IEEE T COMPUT AID D;INT J FOOD MICROBIOL;INTEGR BIOL-UK;J AM CHEM SOC;J BACTERIOL;J CLIN MICROBIOL;J FORENSIC SCI;J R SOC INTERFACE;JALA-J LAB AUTOM;LAB CHIP;LAB CHIP MINIATURIZE;LANGMUIR;METAB ENG;NAT CHEM BIOL;NAT REV DRUG DISCOV;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS BIOL;RSC ADV;US Pat
Ding, Yunfeng;Fan, Jinzhen;Li, Baoqing;Li, Jiannan;Pan, Tingrui;Tan, Cheemeng;Tseng, Kuo Hao;Villarreal, Fernando;Weyers, Brent
2024-03-11 ER
Angenendt, P;Bsoul, A;Cai, L F;Chappell, J;Dittrich, P S;Dutka, F;Fan, J Z;Garamella, J;Grgicak, C M;Gulati, S;Harris, D C;Hayashi, Y;Hedges, A J;Hodgman, C E;Hsieh, Y L;Hu, S W;Huang, J D;Jeon, N L;Kong, F W;La D.;Lee, K;Leung, K;Li, B Q;Li, G W;Mei, Q;Noireaux, V;Oosterbroek E.;Patterson, G H;Rose, D;Schu, D J;Seidi, A;Sharp, P A;Smith, K P;Stögbauer, T;Sun, K;Tan, C;Teh, S Y;Vaughn, B S;Villarreal, F;Yeger-Lotem, E;Zheng, B
EZ1KL
Anhui, Peoples R China;Davis, CA USA.
22
null
2
null
28,613,297
Ding, Yunfeng;Fan, Jinzhen;Li, Baoqing;Li, Jiannan;Pan, Tingrui;Tan, Cheemeng;Tseng, Kuo Hao;Villarreal, Fernando;Weyers, Brent
LAB CHIP
Anhui, Peoples R China;Davis, CA USA
Baym, M;Bronson, R T;Gerber, G K;Giessen, T W;Kerns, S J;Kotula, J W;Niederhuber, M J;Riglar, D T;Silver, P A;Way, J C
10.1038/nbt.3879
null
75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
3zi1h133p6k6d6k53g13n6zw4t3p4u3e6d34
Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation
Harvard Med Sch
null
Silver, PA (corresponding author), Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA.;Silver, PA (corresponding author), Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
null
Baym, Michael;Bronson, Roderick T;Gerber, Georg K;Giessen, Tobias W;Kerns, S Jordan;Kotula, Jonathan W;Niederhuber, Matthew J;Riglar, David T;Silver, Pamela A;Way, Jeffrey C
Biotechnology & Applied Microbiology
NCI Cancer Center Support Grant [NIH 5 P30 CA06516]; Human Frontier Science Program Long-Term Fellowship; NHMRC/RG Menzies Early Career Fellowship from Menzies Foundation through Australian National Health and Medical Research Council; Leopoldina Research Fellowship from German National Academy of Sciences Leopoldina [LPDS 2014-05]; Defense Advanced Research Projects Agency [HR0011-15-C-0094]; Wyss Institute for Biologically Inspired Engineering
WOS
Silver, P A
Emulate Inc, Boston, MA USA;Harvard Med Sch, Boston, MA USA;Harvard Univ, Boston, MA USA;SynLogic, Cambridge, MA USA
35
as;bacteria;can;diagnostics;engineered;function;gut;in;inflammation;live;long-term;mammalian;of;the
1
Baym, Michael;Giessen, Tobias;Riglar, David
NATURE PUBLISHING GROUP
Emulate Inc, Boston, MA USA;Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Massachusetts Host Microbiome Ctr, Boston, MA USA;Harvard Med Sch, Dept Biomed Informat, Boston, MA USA;Harvard Med Sch, Dept Microbiol & Immunol, Boston, MA USA;Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA;Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA.; Silver, PA (corresponding author), Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA;SynLogic, Cambridge, MA USA
Article
Harvard Med Sch;Harvard Univ
NEW YORK
null
null
Emulate Inc;Harvard Med Sch;Harvard Univ;SynLogic
Defense Advanced Research Projects Agency;Human Frontier Science Program Long-Term Fellowship;Leopoldina Research Fellowship from German National Academy of Sciences Leopoldina;NCI Cancer Center Support Grant;NHMRC/RG Menzies Early Career Fellowship from Menzies Foundation through Australian National Health and Medical Research Council;Wyss Institute for Biologically Inspired Engineering
Silver, PA (corresponding author), Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA.; Silver, PA (corresponding author), Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
+
Baym, Michael;Bronson, Roderick T;Gerber, Georg K;Giessen, Tobias W;Kerns, S Jordan;Kotula, Jonathan W;Niederhuber, Matthew J;Riglar, David T;Silver, Pamela A;Way, Jeffrey C
186
7
405,310,300,017
Defense Advanced Research Projects Agency [HR0011-15-C-0094];Human Frontier Science Program Long-Term Fellowship;Leopoldina Research Fellowship from German National Academy of Sciences Leopoldina [LPDS 2014-05];NCI Cancer Center Support Grant [NIH 5 P30 CA06516];NHMRC/RG Menzies Early Career Fellowship from Menzies Foundation through Australian National Health and Medical Research Council;Wyss Institute for Biologically Inspired Engineering
USA
NATURE BIOTECHNOLOGY
USA;USA.;
null
null
Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA
1087-0156
Baym, M;Bronson, R T;Gerber, G K;Giessen, T W;Kerns, S J;Kotula, J W;Niederhuber, M J;Riglar, D T;Silver, P A;Way, J C
JUL
pamela_silver@hms.harvard.edu
bacteria;function;inflammation;live diagnostics;mammalian gut
10
J
Biotechnology & Applied Microbiology
6 months;analysis;BACTERIA;CELL RECRUITMENT;commensal murine Escherichia coli strain;commercial translation;detected tetrathionate;diagnostic strain;diagnostics;disease;durable performance;DYNAMICS;ELECTRON-ACCEPTOR;ENTERICA SEROVAR TYPHIMURIUM;ESCHERICHIA-COLI;exposure;extended gut colonization;fecal testing;function;genetic mouse models;growth;gut;infection-induced;inflammation;live diagnostics;living diagnostics;mammalian gut;MEMORY;MICROBIOTA;mouse gut;mutation;potential;SALMONELLA-TYPHIMURIUM;stable;STRAIN;STRAINS;susceptibility;synthetic genetic circuits;technologies;tetrathionate;therapeutics;time;unpredictable function
Riglar, D T
CELL RECRUITMENT;DISEASE;DYNAMICS;ELECTRON-ACCEPTOR;ENTERICA SEROVAR TYPHIMURIUM;ESCHERICHIA-COLI;GROWTH;MICROBIOTA;SALMONELLA-TYPHIMURIUM;STRAIN
653
[Riglar, David T.; Giessen, Tobias W.; Baym, Michael; Kerns, S. Jordan; Niederhuber, Matthew J.; Kotula, Jonathan W.; Silver, Pamela A.] Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA. [Riglar, David T.; Giessen, Tobias W.; Kerns, S. Jordan; Niederhuber, Matthew J.; Kotula, Jonathan W.; Way, Jeffrey C.; Silver, Pamela A.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Baym, Michael] Harvard Med Sch, Dept Biomed Informat, Boston, MA USA. [Bronson, Roderick T.] Harvard Med Sch, Dept Microbiol & Immunol, Boston, MA USA. [Gerber, Georg K.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Massachusetts Host Microbiome Ctr, Boston, MA USA. [Kerns, S. Jordan] Emulate Inc, Boston, MA USA. [Kotula, Jonathan W.] SynLogic, Cambridge, MA USA.
We thank A. Graveline and L. Bry for discussions and assistance with mouse experiments and A. Verdegaal for experimental assistance. S. typhimurium TT22470 was a gift from J. Roth. We thank Dana-Farber/Harvard Cancer Center in Boston for the use of the Rodent Histopathology Core, which provided histology preparation service. Dana-Farber/Harvard Cancer Center is supported in part by a NCI Cancer Center Support Grant # NIH 5 P30 CA06516. D.T.R. was supported by a Human Frontier Science Program Long-Term Fellowship and an NHMRC/RG Menzies Early Career Fellowship from the Menzies Foundation through the Australian National Health and Medical Research Council. T.W.G. was supported by a Leopoldina Research Fellowship (LPDS 2014-05) from the German National Academy of Sciences Leopoldina. The research was funded by Defense Advanced Research Projects Agency Grant HR0011-15-C-0094 (P.A.S.) and the Wyss Institute for Biologically Inspired Engineering.
6 months;analysis;bacteria;commensal murine Escherichia coli strain;commercial translation;detected tetrathionate;diagnostic strain;diagnostics;durable performance;exposure;extended gut colonization;fecal testing;function;genetic mouse models;gut;infection-induced;inflammation;living diagnostics;mammalian gut;memory;mouse gut;mutation;potential;stable;strain;strains;susceptibility;synthetic genetic circuits;technologies;tetrathionate;therapeutics;time;unpredictable function
10.1007/978-1-4939-0554-6_12;10.1007/s00011-008-7062-5;10.1016/j.addr.2016.04.032;10.1016/j.cels.2015.06.001;10.1016/j.chom.2015.12.006;10.1016/S0008-6215(00)90109-5;10.1021/sb3000595;10.1021/sb3000832;10.1021/sb400055h;10.1021/sb4001245;10.1038/35002131;10.1038/embor.2013.27;10.1038/ismej.2014.3;10.1038/nature09415;10.1038/nature11225;10.1038/ncomms10039;10.1046/j.1365-2958.1999.01345.x;10.1073/pnas.120163297;10.1073/pnas.1210309109;10.1073/pnas.1321321111;10.1086/315497;10.1097/MIB.0000000000000468;10.1111/mmi.12176;10.1126/science.1256272;10.1128/IAI.71.5.2839-2858.2003;10.1128/JB.183.8.2463-2475.2001;10.1136/gut.34.7.865;10.1186/1754-1611-4-12;10.1186/s13059-016-0980-6;10.1371/journal.pone.0044328;10.1371/journal.pone.0128036;10.4049/jimmunol.168.2.869;[10.1038/NMETH.3147, 10.1038/nmeth.3147];[10.1038/NMETH.3339, 10.1038/nmeth.3339]
Harvard Med Sch
Baym, M;Bronson, R T;Gerber, G K;Giessen, T W;Kerns, S J;Kotula, J W;Niederhuber, M J;Riglar, D T;Silver, P A;Way, J C
Riglar, D T: Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA
Young, Richard A
HR0011-15-C-0094;LPDS 2014-05;NIH 5 P30 CA06516
36
null
USA
Emulate Inc;Harvard Med Sch;Harvard Univ;SynLogic
Riglar, David T
Green Accepted
CELL RECRUITMENT;DISEASE;DYNAMICS;ELECTRON-ACCEPTOR;ENTERICA SEROVAR TYPHIMURIUM;ESCHERICHIA-COLI;GROWTH;MICROBIOTA;SALMONELLA-TYPHIMURIUM;STRAIN
Riglar, David T.; Giessen, Tobias W.; Baym, Michael; Kerns, S. Jordan; Niederhuber, Matthew J.; Bronson, Roderick T.; Kotula, Jonathan W.; Gerber, Georg K.; Way, Jeffrey C.; Silver, Pamela A.;
null
Emulate Inc, Boston, MA USA;Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Massachusetts Host Microbiome Ctr, Boston, MA USA;Harvard Med Sch, Dept Biomed Informat, Boston, MA USA;Harvard Med Sch, Dept Microbiol & Immunol, Boston, MA USA;Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA;SynLogic, Cambridge, MA USA
Emulate Inc, Boston, MA USA;Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Massachusetts Host Microbiome Ctr, Boston, MA USA;Harvard Med Sch, Dept Biomed Informat, Boston, MA USA;Harvard Med Sch, Dept Microbiol & Immunol, Boston, MA USA;Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA;SynLogic, Cambridge, MA USA
1546-1696
null
7
1980;1986;1993;1998;1999;2000;2001;2002;2003;2008;2010;2012;2013;2014;2015;2016
202
Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
Nat. Biotechnol.
Silver, Pamela A
NATURE PUBLISHING GROUP
,;6;a;accomplish;analysis;and;as;bacteria;bacterial;be;been;both;but;by;can;circuits;coli;colonization;commensal;commercial;confirms;detect;detected;diagnostic;diagnostics;durable;during;engineered;Escherichia;exposure;extended;fecal;for;function;functioned;genetic;genetically;gut;has;here;hindered;in;infection-induced;inflammation;intended;is;living;maintain;mammalian;memory;models;months;mouse;murine;mutation;of;or;our;over;performance;potential;produced;report;retains;stable;strain;strains;susceptibility;synthetic;technologies;testing;tetrathionate;that;the;their;therapeutics;these;this;time;to;translation;unpredictable;using;we;were;which
Harvard Med Sch;Harvard Univ
Bacteria can be engineered to function as diagnostics or therapeutics in the mammalian gut but commercial translation of technologies to accomplish this has been hindered by the susceptibility of synthetic genetic circuits to mutation and unpredictable function during extended gut colonization. Here, we report stable, engineered bacterial strains that maintain their function for 6 months in the mouse gut. We engineered a commensal murine Escherichia coli strain to detect tetrathionate, which is produced during inflammation. Using our engineered diagnostic strain, which retains memory of exposure in the gut for analysis by fecal testing, we detected tetrathionate in both infection-induced and genetic mouse models of inflammation over 6 months. The synthetic genetic circuits in the engineered strain were genetically stable and functioned as intended over time. The durable performance of these strains confirms the potential of engineered bacteria as living diagnostics.
F-6495-2012
CELL RECRUITMENT;DISEASE;DYNAMICS;ELECTRON-ACCEPTOR;ENTERICA SEROVAR TYPHIMURIUM;ESCHERICHIA-COLI;GROWTH;MICROBIOTA;SALMONELLA-TYPHIMURIUM;STRAINS
17
null
null
8
ESCHERICHIA-COLI;CELL RECRUITMENT;DISEASE;DYNAMICS;ELECTRON-ACCEPTOR;ENTERICA SEROVAR TYPHIMURIUM;GROWTH;MICROBIOTA;SALMONELLA-TYPHIMURIUM;STRAINS
WOS:000405310300017
Emulate Inc, Boston, MA USA;Harvard Med Sch, Boston, MA USA;Harvard Univ, Boston, MA USA;SynLogic, Cambridge, MA USA
USA
2,017
null
0000-0001-6328-2031;0000-0002-5004-4373;0000-0003-1303-5598
null
null
English
null
ACS SYNTH BIOL;ADV BACTERIAL GENET;ADV DRUG DELIVER REV;CARBOHYD RES;CELL HOST MICROBE;CELL SYST;EMBO REP;GENETICS;GENOME BIOL;GUT;INFECT IMMUN;INFLAMM BOWEL DIS;INFLAMM RES;ISME J;J BACTERIOL;J Biol Eng;J IMMUNOL;J INFECT DIS;METHODS MOL BIOL;MOL MICROBIOL;NAT COMMUN;NAT METHODS;NATURE;P NATL ACAD SCI USA;PLOS ONE;SCIENCE
Baym, Michael;Bronson, Roderick T;Gerber, Georg K;Giessen, Tobias W;Kerns, S Jordan;Kotula, Jonathan W;Niederhuber, Matthew J;Riglar, David T;Silver, Pamela A;Way, Jeffrey C
2024-03-11 ER
Archer, E J;Barthel, M;Baym, M;Bucci, V;Ceroni, F;Chassaing, B;Clairmont, C;Datsenko, K A;Davis R.W.;Deatherage, D E;Devkota, S;Drake, J W;Farzadfard, F;Gardner, T S;Gorochowski, T E;Hensel, M;Hoover-Plow, J L;Kamdar, K;Keubler, L M;Kotula, J W;Kuo, M S;Lee, H;Liu, Y W;Mimee, M;Moser, F;Myhrvold, C;Price-Carter, M;Rooks, M G;Simmonds, N J;Sleight Sean, C;Sleight, S C;White, P;Winter, S E;Yang, L
FA2ZJ
Boston, MA USA;Boston, MA USA.
264
null
4
null
28,553,941
Baym, Michael;Bronson, Roderick T;Gerber, Georg K;Giessen, Tobias W;Kerns, S Jordan;Kotula, Jonathan W;Niederhuber, Matthew J;Riglar, David T;Silver, Pamela A;Way, Jeffrey C
NAT BIOTECHNOL
Boston, MA USA;Cambridge, MA USA
Dana, S K;Hellen, E H;Kurths, J
10.1140/epjst/e2016-60396-5
null
TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
3h3d734633m6n4gh6b56u663414r16k61s
Electronic circuit analog of synthetic genetic networks: Revisited
Univ North Carolina Greensboro
null
Hellen, EH (corresponding author), Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA.
null
Dana, Syamal K;Hellen, Edward H;Kurths, Jurgen
Physics, Multidisciplinary
University Grants Commission (India) Emeritus Fellowship
WOS
Hellen, E H
Jadavpur Univ, Kolkata, India;Potsdam Inst Climate Impact Res, Potsdam, Germany;Univ North Carolina Greensboro, Greensboro, NC USA
226
:;analog;circuit;electronic;genetic;networks;of;Revisited;synthetic
3
Hellen, Edward
SPRINGER HEIDELBERG
Jadavpur Univ, Dept Math, Kolkata 700032, India;Potsdam Inst Climate Impact Res, Potsdam, Germany;Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA
Article
Univ North Carolina Greensboro
HEIDELBERG
null
null
Jadavpur Univ;Potsdam Inst Climate Impact Res;Univ North Carolina Greensboro
University Grants Commission (India) Emeritus Fellowship
Hellen, EH (corresponding author), Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA.
1828
Dana, Syamal K;Hellen, Edward H;Kurths, Jurgen
4
3
403,684,400,010
University Grants Commission (India) Emeritus Fellowship
Germany;India;USA
EUROPEAN PHYSICAL JOURNAL-SPECIAL TOPICS
USA
null
null
Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA
1951-6355
Dana, S K;Hellen, E H;Kurths, J
JUN
ehhellen@uncg.edu
electronic circuit analog;synthetic genetic networks
3
J
Physics
3-gene Repressilator;additive noise;chemical kinetics;circuit design;circuit models;conversions;coupled Repressilators;dynamical behavior's complexity;DYNAMICAL BEHAVIORS;dynamical systems' behavior;electrical systems;electronic analog;electronic circuit analog;electronic circuits;experiment;experiments;extrinsic noise;Hill function inhibition;important features;improved electronic analog;improved version;incorporation;initial conditions;investigations;isolated Repressilator;model parameters;multistability;networks;numerical results;numerical simulations;previous design;quorum sensing coupling;real circuit component values;REPRESSILATORS;studies;studying potential dynamical behaviors;SYNCHRONIZATION;synthetic genetic network;synthetic genetic networks;systematic change;useful tools;verification
Hellen, E H
REPRESSILATORS;SYNCHRONIZATION
1811
[Hellen, Edward H.] Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA. [Kurths, Jurgen] Potsdam Inst Climate Impact Res, Potsdam, Germany. [Dana, Syamal K.] Jadavpur Univ, Dept Math, Kolkata 700032, India.
S.K.D. acknowledges support by the University Grants Commission (India) Emeritus Fellowship. The authors thank Evgeny Volkov for valuable contributions.
3-gene Repressilator;additive noise;chemical kinetics;circuit design;circuit models;conversions;coupled Repressilators;dynamical behavior's complexity;dynamical behaviors;dynamical systems' behavior;electrical systems;electronic analog;electronic circuits;experiment;experiments;extrinsic noise;Hill function inhibition;important features;improved electronic analog;improved version;incorporation;initial conditions;investigations;isolated Repressilator;model parameters;multistability;networks;numerical results;numerical simulations;previous design;quorum sensing coupling;real circuit component values;studies;studying potential dynamical behaviors;synthetic genetic network;synthetic genetic networks;systematic change;useful tools;verification
10.1038/35002125;10.1038/35002131;10.1038/468889a;10.1038/nrg3197;10.1038/scientificamerican1293-102;10.1063/1.1345702;10.1063/1.1786683;10.1063/1.2173048;10.1063/1.4705085;10.1073/pnas.0307095101;10.1103/PhysRevE.78.031904;10.1103/PhysRevE.83.031901;10.1103/PhysRevE.95.022408;10.1103/PhysRevLett.99.148103;10.1142/S0218127407019275;10.1142/S0218127410026800;10.1146/annurev.cellbio.21.012704.131001;10.1371/journal.pone.0023286;10.1371/journal.pone.0062997;10.1371/journal.pone.0076032
Univ North Carolina Greensboro
Dana, S K;Hellen, E H;Kurths, J
Hellen, E H: Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA
Hellen, Edward
null
21
null
USA
Jadavpur Univ;Potsdam Inst Climate Impact Res;Univ North Carolina Greensboro
Hellen, Edward H
Green Submitted
REPRESSILATORS;SYNCHRONIZATION
Hellen, Edward H.; Kurths, Jurgen; Dana, Syamal K.;
null
Jadavpur Univ, Dept Math, Kolkata 700032, India;Potsdam Inst Climate Impact Res, Potsdam, Germany;Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA
Jadavpur Univ, Dept Math, Kolkata 700032, India;Potsdam Inst Climate Impact Res, Potsdam, Germany;Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA
1951-6401
null
9
1993;2000;2001;2002;2004;2005;2006;2007;2008;2010;2011;2012;2013;2017
4
Univ North Carolina Greensboro, Dept Phys & Astron, Greensboro, NC 27402 USA
Eur. Phys. J.-Spec. Top.
Dana, Syamal K
SPRINGER HEIDELBERG
,;3-gene;a;additive;allows;an;analog;and;are;behavior;behavior's;behaviors;between;change;chemical;circuit;circuits;complementary;complexity;component;conditions;conversions;coupled;coupling;critically;design;dynamical;electrical;electronic;especially;experiment;experiments;extend;extrinsic;features;for;framework;from;function;genetic;here;Hill;important;improved;in;include;includes;incorporation;inhibition;initial;intrinsic;investigations;is;isolated;it;kinetics;make;mimic;model;models;multistability;network;networks;noise;numerical;of;our;parameters;particularly;potential;presence;present;previous;providing;quorum;real;representing;repressilator;Repressilators;results;reveal;sensing;show;shows;simulations;studies;studying;synthetic;systematic;systems;systems';that;the;this;to;tools;us;useful;values;verification;version;we;when;which
Univ North Carolina Greensboro
Electronic circuits are useful tools for studying potential dynamical behaviors of synthetic genetic networks. The circuit models are complementary to numerical simulations of the networks, especially providing a framework for verification of dynamical behaviors in the presence of intrinsic and extrinsic noise of the electrical systems. Here we present an improved version of our previous design of an electronic analog of genetic networks that includes the 3-gene Repressilator and we show conversions between model parameters and real circuit component values to mimic the numerical results in experiments. Important features of the circuit design include the incorporation of chemical kinetics representing Hill function inhibition, quorum sensing coupling, and additive noise. Especially, we make a circuit design for a systematic change of initial conditions in experiment, which is critically important for studies of dynamical systems' behavior, particularly, when it shows multistability. This improved electronic analog of the synthetic genetic network allows us to extend our investigations from an isolated Repressilator to coupled Repressilators and to reveal the dynamical behavior's complexity.
AAN-7714-2021
REPRESSILATORS;SYNCHRONIZATION
0
null
null
18
repressilator;SYNCHRONIZATION
WOS:000403684400010
Jadavpur Univ, Kolkata, India;Potsdam Inst Climate Impact Res, Potsdam, Germany;Univ North Carolina Greensboro, Greensboro, NC USA
Germany;India;USA
2,017
null
0000-0001-5060-7220
null
null
English
null
ANNU REV CELL DEV BI;CHAOS;INT J BIFURCAT CHAOS;NAT REV GENET;NATURE;P NATL ACAD SCI USA;PHYS REV E;PHYS REV LETT;PLOS ONE;SCI AM;SIMULATING ANAL ANIM
Dana, Syamal K;Hellen, Edward H;Kurths, Jurgen
2024-03-11 ER
Benenson, Y;Buldu, J M;Elowitz, M;Elowitz, M B;Ermentrout G. B.;Garcia-Ojalvo, J;Gardner, T S;Hasty, J;Hellen, E H;Mason, J;Potapov, I;Strogatz, S H;Tokuda, I T;Ullner, E;Wagemakers, A;Waters, C M
EY0XO
Greensboro, NC USA
4
null
3
null
null
Dana, Syamal K;Hellen, Edward H;Kurths, Jurgen
EUR PHYS J-SPEC TOP
Greensboro, NC USA;Kolkata, India;Potsdam, Germany
Kurths, J;Wang, H Y;Wu, J;Xu, Y
10.1063/1.4984806
063105
1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
5w3f4a16h34176x3p1d3x2n1h20g03g343566
Information-based measures for logical stochastic resonance in a synthetic gene network under Levy flight superdiffusion
Northwestern Polytech Univ
null
Xu, Y (corresponding author), Beifang Univ Nationalities, Sch Math & Informat Sci, Yinchuan 750021, Peoples R China.;Xu, Y (corresponding author), Humboldt Univ, Dept Phys, D-12489 Berlin, Germany.;Xu, Y (corresponding author), Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China.;Xu, Y (corresponding author), Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany.
null
Kurths, Juergen;Wang, Haiyan;Wu, Juan;Xu, Yong
Mathematics, Applied;Physics, Mathematical
National Natural Science Foundation of China [11602003, 11372247]
WOS
Xu, Y
Beifang Univ Nationalities, Yinchuan, Peoples R China;Humboldt Univ, Berlin, Germany;Northwestern Polytech Univ, Xian, Peoples R China;Potsdam Inst Climate Impact Res, Potsdam, Germany
27
a;flight;for;gene;in;information-based;Levy;logical;measures;network;resonance;stochastic;superdiffusion;synthetic;under
2
Kurths, Juergen;Xu, Yong
AMER INST PHYSICS
Beifang Univ Nationalities, Sch Math & Informat Sci, Yinchuan 750021, Peoples R China;Humboldt Univ, Dept Phys, D-12489 Berlin, Germany;Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China;Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China.; Xu, Y (corresponding author), Beifang Univ Nationalities, Sch Math & Informat Sci, Yinchuan 750021, Peoples R China.; Xu, Y (corresponding author), Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany.; Xu, Y (corresponding author), Humboldt Univ, Dept Phys, D-12489 Berlin, Germany;Northwestern Polytech Univ, Sch Marine Sci & Technol, Xian 710072, Peoples R China;Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany
Article
Beifang Univ Nationalities;Humboldt Univ;Northwestern Polytech Univ;Potsdam Inst Climate Impact Res
MELVILLE
null
null
Beifang Univ Nationalities;Humboldt Univ;Northwestern Polytech Univ;Potsdam Inst Climate Impact Res
National Natural Science Foundation of China
Xu, Y (corresponding author), Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China.; Xu, Y (corresponding author), Beifang Univ Nationalities, Sch Math & Informat Sci, Yinchuan 750021, Peoples R China.; Xu, Y (corresponding author), Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany.; Xu, Y (corresponding author), Humboldt Univ, Dept Phys, D-12489 Berlin, Germany.
null
Kurths, Juergen;Wang, Haiyan;Wu, Juan;Xu, Yong
38
5
404,630,200,007
National Natural Science Foundation of China [11602003, 11372247]
China;Germany
CHAOS
China;Germany
null
null
Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China
1054-1500
Kurths, J;Wang, H Y;Wu, J;Xu, Y
JUN
hsux3@nwpu.edu.cn
information-based measures;Levy flight superdiffusion;logical stochastic resonance;synthetic gene network
4
J
Mathematics;Physics
accomplished logical stochastic resonance;AIP Publishing;DYNAMICS;information-based measures;information-based methodology;Levy flight superdiffusion;Levy noise;logic gates;logical information transmission;LOGICAL STOCHASTIC RESONANCE;MODEL;mutual information;mutual information changes;noise;noise entropy;potential;repressive proteins;square wave signal;stochastic synthetic gene network model;symbol error rate;synchronization degree;synchronization variances;synthetic gene network;SYSTEM;toggle switch;two repressive proteins
Wu, J
DYNAMICS;MODEL;NOISE;SYSTEM;toggle switch
null
[Wu, Juan; Xu, Yong] Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China. [Wu, Juan; Xu, Yong] Beifang Univ Nationalities, Sch Math & Informat Sci, Yinchuan 750021, Peoples R China. [Wu, Juan; Xu, Yong; Kurths, Juergen] Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany. [Xu, Yong; Kurths, Juergen] Humboldt Univ, Dept Phys, D-12489 Berlin, Germany. [Wang, Haiyan] Northwestern Polytech Univ, Sch Marine Sci & Technol, Xian 710072, Peoples R China.
This work was supported by the National Natural Science Foundation of China under Grant Nos. 11602003 and 11372247. Y. Xu acknowledges the Alexander von Humboldt Foundation and the Fundamental Research Funds for the Central Universities.
accomplished logical stochastic resonance;AIP Publishing;information-based methodology;Levy flight superdiffusion;Levy noise;logic gates;logical information transmission;logical stochastic resonance;mutual information;mutual information changes;noise entropy;potential;repressive proteins;square wave signal;stochastic synthetic gene network model;symbol error rate;synchronization degree;synchronization variances;synthetic gene network;two repressive proteins
10.1007/s10955-013-0782-0;10.1007/s11071-012-0473-4;10.1007/s11071-013-1136-9;10.1007/s11431-015-6001-2;10.1016/j.bpj.2011.11.4000;10.1016/j.chaos.2016.09.015;10.1016/j.cnsns.2012.07.010;10.1016/j.physa.2014.08.042;10.1016/j.physrep.2006.12.004;10.1038/35002131;10.1038/srep31505;10.1063/1.3660159;10.1063/1.4775758;10.1063/1.4945420;10.1063/1.4948461;10.1073/pnas.0402940101;10.1073/pnas.040411297;10.1088/1751-8113/40/26/005;10.1103/PhysRevE.83.041909;10.1103/PhysRevE.88.052721;10.1103/PhysRevE.94.042222;10.1103/PhysRevLett.102.104101;10.1142/S021797920603576X;10.1142/S0217979214502233;10.1142/S0218127408021877;10.1186/1752-0509-1-50;10.1209/0295-5075/113/30009;10.1209/0295-5075/93/50001;10.1371/journal.pone.0016168;10.1371/journal.pone.0076032
Northwestern Polytech Univ
Kurths, J;Wang, H Y;Wu, J;Xu, Y
Wu, J: Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China
Xu, Yong
11372247;11602003
33
null
China
Beifang Univ Nationalities;Humboldt Univ;Northwestern Polytech Univ;Potsdam Inst Climate Impact Res
Wu, Juan
null
DYNAMICS;MODEL;NOISE;SYSTEM;TOGGLE SWITCH
Wu, Juan; Xu, Yong; Wang, Haiyan; Kurths, Juergen;
null
Beifang Univ Nationalities, Sch Math & Informat Sci, Yinchuan 750021, Peoples R China;Humboldt Univ, Dept Phys, D-12489 Berlin, Germany;Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China;Northwestern Polytech Univ, Sch Marine Sci & Technol, Xian 710072, Peoples R China;Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany
Beifang Univ Nationalities, Sch Math & Informat Sci, Yinchuan 750021, Peoples R China;Humboldt Univ, Dept Phys, D-12489 Berlin, Germany;Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China;Northwestern Polytech Univ, Sch Marine Sci & Technol, Xian 710072, Peoples R China;Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany
1089-7682
null
6
1982;1986;1994;2000;2004;2006;2007;2008;2009;2011;2012;2013;2014;2016
36
Beifang Univ Nationalities, Sch Math & Informat Sci, Yinchuan 750021, Peoples R China;Humboldt Univ, Dept Phys, D-12489 Berlin, Germany;Northwestern Polytech Univ, Dept Appl Math, Xian 710072, Peoples R China;Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany
Chaos
Kurths, Juergen
AMER INST PHYSICS
";,;a;accomplished;achieve;addition;AIP;almost;an;analyze;and;as;based;between;by;calculate;can;caused;changes;complementary;consequently;degree;demonstrate;driven;entropy;error;first;flight;for;furthermore;gates;gene;in;information;information-based;investigate;Levy;logic;logical;methodology;model;mutual;network;noise;numerically;obtain;of;off;on;potential;present;proteins;published;Publishing;quantify;rate;repressive;resonance;reveal;shown;shows;signal;some;square;states;stochastic;superdiffusion;symbol;synchronization;synchronously;synthetic;that;the;then;theoretically;those;to;transmission;two;under;variances;wave;we;well;which
Beifang Univ Nationalities;Humboldt Univ;Northwestern Polytech Univ;Potsdam Inst Climate Impact Res
We investigate the logical information transmission of a synthetic gene network under Levy flight superdiffusion by an information-based methodology. We first present the stochastic synthetic gene network model driven by a square wave signal under Levy noise caused by Levy flight superdiffusion. Then, to quantify the potential of logical information transmission and logical stochastic resonance, we theoretically obtain an information-based methodology of the symbol error rate, the noise entropy, and the mutual information of the logical information transmission. Consequently, based on the complementary "on" and "off" states shown in the logical information transmission for the repressive proteins, we numerically calculate the symbol error rate for logic gates, which demonstrate that the synthetic gene network under Levy noise can achieve some logic gates as well as logical stochastic resonance. Furthermore, we calculate the noise entropy and the mutual information between the square wave signal and the logical information transmission, which reveal and quantify the potential of logical information transmission and logical stochastic resonance. In addition, we analyze the synchronization degree of the mutual information for the accomplished logical stochastic resonance of two repressive proteins of the synthetic gene network by synchronization variances, which shows that those mutual information changes almost synchronously. Published by AIP Publishing.
D-7348-2017
DYNAMICS;MODEL;NOISE;SYSTEM;TOGGLE SWITCH
1
null
null
9
DYNAMICS;MODEL;NOISE;SYSTEM;toggle switch
WOS:000404630200007
Beifang Univ Nationalities, Yinchuan, Peoples R China;Humboldt Univ, Berlin, Germany;Northwestern Polytech Univ, Xian, Peoples R China;Potsdam Inst Climate Impact Res, Potsdam, Germany
China;Germany
2,017
null
0000-0002-5926-4276;0000-0002-8407-4650
null
null
English
null
BIOPHYS J;BMC SYST BIOL;CHAOS;CHAOS SOLITON FRACT;COMMUN NONLINEAR SCI;EPL-EUROPHYS LETT;INT J BIFURCAT CHAOS;INT J MOD PHYS B;J CHEM PHYS;J PHYS A-MATH THEOR;J STAT PHYS;LEVY WALKS VERSUS LE;NATURE;NONLINEAR DYNAM;P NATL ACAD SCI USA;PHYS REP;PHYS REV E;PHYS REV LETT;PHYSICA A;PLOS ONE;SCI CHINA TECHNOL SC;SCI REP-UK;SIMULATION CHAOTIC B;The fractal geometry of nature
Kurths, Juergen;Wang, Haiyan;Wu, Juan;Xu, Yong
2024-03-11 ER
Ando, H;Andrecut, M;Bianco-Martinez, E;Chen, H;Dari, A;Daza, A;Dubkov, A A;Gardner, T S;Hasty, J;Hellen, E H;Hlavácková-Schindler, K;Janicki, A;Klafter, J;Kobayashi, H;Li, Y G;Mandelbrot B. B.;Murali, K;Nurzaman, S G;Sharma, A;Strasser, M;Wang, J W;Wang, Z Q;Xu, Y;Zeng, C H;Zeng, L Z
EZ3SH
Berlin, Germany;Potsdam, Germany.;Xian, Peoples R China.;Yinchuan, Peoples R China.
39
null
4
null
28,679,222
Kurths, Juergen;Wang, Haiyan;Wu, Juan;Xu, Yong
CHAOS
Berlin, Germany;Potsdam, Germany;Xian, Peoples R China;Yinchuan, Peoples R China
Allgöwer, F;Halter, W;Montenbruck, J M;Tuza, Z A
10.1016/j.jtbi.2017.03.004
null
24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
a4e3a4d2g2s4g364214184t2962c2x6y6s4434
A resource dependent protein synthesis model for evaluating synthetic circuits
Univ Stuttgart
null
Halter, W (corresponding author), Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany.
null
Allgoewer, Frank;Halter, Wolfgang;Montenbruck, Jan Maximilian;Tuza, Zoltan A
Biology;Mathematical & Computational Biology
Ministry for Science, Research and Art Baden-Wurttemberg
WOS
Halter, W
Univ Stuttgart, Stuttgart, Germany
420
a;circuits;dependent;evaluating;for;model;protein;resource;synthesis;synthetic
1
Allgöwer, Frank;Halter, Wolfgang
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany
Article
Univ Stuttgart
LONDON
null
null
Univ Stuttgart
Ministry for Science, Research and Art Baden-Wurttemberg
Halter, W (corresponding author), Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany.
278
Allgoewer, Frank;Halter, Wolfgang;Montenbruck, Jan Maximilian;Tuza, Zoltan A
4
1
400,952,700,027
Ministry for Science, Research and Art Baden-Wurttemberg
Germany
JOURNAL OF THEORETICAL BIOLOGY
Germany
null
null
Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany
0022-5193
Allgöwer, F;Halter, W;Montenbruck, J M;Tuza, Z A
MAY 7
wolfgang.halter@ist.uni-stuttgart.de
resource dependent protein synthesis model;synthetic circuits
4
J
Life Sciences & Biomedicine - Other Topics;Mathematical & Computational Biology
convergence properties;different loading scenarios;DNA templates;dynamic mechanisms;DYNAMICS;expression;Genetic regulatory networks;geometric considerations;host-circuit interactions;influence;limited resources;LIVE ESCHERICHIA-COLI;movement;mRNA;Normally hyperbolic manifolds;novel approaches;novel protein synthesis;present additional insights;process;protein synthesis;Resource dependence;resource dependent protein synthesis model;Ribosome Flow Model;RIBOSOMES;RNA-POLYMERASE;silico design;synthetic biology;synthetic circuits;synthetic gene circuits;synthetic gene networks
Halter, W
DYNAMICS;EXPRESSION;Genetic regulatory networks;host-circuit interactions;LIVE ESCHERICHIA-COLI;Normally hyperbolic manifolds;Resource dependence;RNA-POLYMERASE;Synthetic biology
267
[Halter, Wolfgang; Montenbruck, Jan Maximilian; Tuza, Zoltan A.; Allgoewer, Frank] Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany.
This work was supported by the research cluster BW<SUP>2</SUP> (www.bwbiosyn.de) of the Ministry for Science, Research and Art Baden-Wurttemberg.
convergence properties;different loading scenarios;DNA templates;dynamic mechanisms;geometric considerations;influence;limited resources;movement;mRNA;novel approaches;novel protein synthesis;present additional insights;process;protein synthesis;Ribosome Flow Model;ribosomes;RNA-polymerase;silico design;synthetic gene circuits;synthetic gene networks
10.1006/jsbi.1997.3845;10.1007/BF01403247;10.1016/0022-2836(77)90279-0;10.1016/j.bpj.2013.10.024;10.1016/j.bpj.2015.06.034;10.1016/j.ydbio.2008.10.043;10.1021/acssynbio.6b00040;10.1038/35002125;10.1038/ismej.2012.94;10.1073/pnas.1416533112;10.1073/pnas.94.3.814;10.1090/S0002-9939-1960-0121542-7;10.1093/nar/25.4.787;10.1093/nar/gkf549;10.1093/nar/gkp889;10.1098/rsif.2014.0713;10.1098/rsif.2015.1062;10.1103/PhysRevE.68.021910;10.1109/TBCAS.2013.2290063;10.1109/TCBB.2012.88;10.1111/j.1365-2958.2012.08081.x;10.1126/science.282.5390.902;10.1128/ecosal.5.2.3;10.1128/JB.181.20.6425-6440.1999;10.1137/0513013;10.1371/journal.pcbi.1002127;10.1371/journal.pone.0096039
Univ Stuttgart
Allgöwer, F;Halter, W;Montenbruck, J M;Tuza, Z A
Halter, W: Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany
Allgöwer, Frank;Tuza, Zoltan Andras
null
31
null
Germany
Univ Stuttgart
Halter, Wolfgang
Green Submitted
DYNAMICS;EXPRESSION;LIVE ESCHERICHIA-COLI;RNA-POLYMERASE
Halter, Wolfgang; Montenbruck, Jan Maximilian; Tuza, Zoltan A.; Allgoewer, Frank;
null
Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany
Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany
1095-8541
host-circuit interactions;Genetic regulatory networks;Normally hyperbolic manifolds;Resource dependence;Synthetic biology
null
1960;1967;1970;1977;1982;1997;1998;1999;2000;2002;2003;2008;2009;2010;2011;2012;2013;2014;2015;2016
4
Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, Stuttgart, Germany
J. Theor. Biol.
Allgoewer, Frank
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
,;a;additional;among;analyzing;and;approaches;based;be;by;can;circuits;considerations;convergence;demonstrate;describes;design;different;DNA;dynamic;evaluate;flow;from;further;gene;geometric;how;in;influence;insights;into;limited;loading;mechanisms;model;movement;mRNA;necessitates;networks;novel;of;on;originates;other;performance;present;process;properties;protein;reliable;resources;respectively;Ribosome;ribosomes;RNA-polymerase;scenarios;silico;such;synthesis;synthetic;templates;the;things;this;to;under;upon;used;we;which
Univ Stuttgart
Reliable in silico design of synthetic gene networks necessitates novel approaches to model the process of protein synthesis under the influence of limited resources. We present such a novel protein synthesis model which originates from the Ribosome Flow Model and among other things describes the movement of RNA-polymerase and ribosomes on mRNA and DNA templates, respectively. By analyzing the convergence properties of this model based upon geometric considerations, we present additional insights into the dynamic mechanisms of the process of protein synthesis. Further, we demonstrate how this model can be used to evaluate the performance of synthetic gene circuits under different loading scenarios.
F-3909-2011;G-2627-2014
DYNAMICS;EXPRESSION;LIVE ESCHERICHIA-COLI;RNA-POLYMERASE
0
null
Genetic regulatory networks;host-circuit interactions;Normally hyperbolic manifolds;Resource dependence;Synthetic biology
12
host-circuit interactions;DYNAMICS;EXPRESSION;Genetic regulatory networks;LIVE ESCHERICHIA-COLI;Normally hyperbolic manifolds;Resource dependence;RNA-POLYMERASE;Synthetic biology
WOS:000400952700027
Univ Stuttgart, Stuttgart, Germany
Germany
2,017
null
0000-0001-9902-5782;0000-0002-3702-3658
null
null
English
null
ACS SYNTH BIOL;BIOPHYS J;DEV BIOL;Die Grundlehren der mathematischen Wissenschaften;ECOSAL PLUS;IEEE ACM T COMPUT BI;IEEE T BIOMED CIRC S;INVENT MATH;ISME J;J BACTERIOL;J MOL BIOL;J R SOC INTERFACE;J STRUCT BIOL;MOL MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV E;PLOS COMPUT BIOL;PLOS ONE;Proc Amer Math Soc;SCIENCE;SIAM J MATH ANAL;The theory of matrices
Allgoewer, Frank;Halter, Wolfgang;Montenbruck, Jan Maximilian;Tuza, Zoltan A
2024-03-11 ER
[Anonymous];Bakshi, S;Bremer Hans;De-Leon, S B T;Edri, S;Elowitz, M B;Gantmacher F.R.;Gorochowski, T E;Gyorgy, A;Hahn W.;Hartman, P;Hirsch, M W;Kennell, D;Margaliot, M;Mcadams, H H;Milo, R;Moran, M A;Poker, G;Pugh, C;Raveh, A;Reuveni, S;Rogozin, I B;Selby, C P;Shaw, L B;Tao, H;Wang, M D;Weisse, A Y;Zhu, J
EU3TA
Stuttgart, Germany
4
null
1
null
28,286,216
Allgoewer, Frank;Halter, Wolfgang;Montenbruck, Jan Maximilian;Tuza, Zoltan A
J THEOR BIOL
Stuttgart, Germany
Dapper, A L;Drury, D W;Siniard, D J;Wade, M J;Zentner, G E
10.1126/sciadv.1601910
e1601910
1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
e3p4k3g38582468324z5d6j1l4u3iw4135f1f
CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations
Indiana Univ
null
Wade, MJ (corresponding author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
null
Dapper, Amy L;Drury, Douglas W;Siniard, Dylan J;Wade, Michael J;Zentner, Gabriel E
Multidisciplinary Sciences
Indiana University startup funds [NIH R01 GM084238]; NSF Doctora lDissertation Improvement Grant [1311167]; Division Of Environmental Biology; Direct For Biological Sciences [1311167] Funding Source: National Science Foundation
WOS
Wade, M J
Indiana Univ, Bloomington, IN USA;Univ Wisconsin, Madison, WI USA
3
and;CRISPR/Cas9;Drives;gene;genetically;in;mating;nonrandomly;populations;variable;wild
1
Zentner, Gabriel
AMER ASSOC ADVANCEMENT SCIENCE
Indiana Univ, Dept Biol, Bloomington, IN 47405 USA;Univ Wisconsin, Genet Lab, Madison, WI 53706 USA
Article
Indiana Univ
WASHINGTON
null
null
Indiana Univ;Univ Wisconsin
Direct For Biological Sciences;Division Of Environmental Biology;Indiana University startup funds;NSF Doctora lDissertation Improvement Grant
Wade, MJ (corresponding author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
null
Dapper, Amy L;Drury, Douglas W;Siniard, Dylan J;Wade, Michael J;Zentner, Gabriel E
23
2
401,955,300,006
Direct For Biological Sciences [1311167] Funding Source: National Science Foundation;Division Of Environmental Biology;Indiana University startup funds [NIH R01 GM084238];NSF Doctora lDissertation Improvement Grant [1311167]
USA
SCIENCE ADVANCES
USA
null
null
Indiana Univ, Dept Biol, Bloomington, IN 47405 USA
2375-2548
Dapper, A L;Drury, D W;Siniard, D J;Wade, M J;Zentner, G E
MAY
mjwade@indiana.edu
CRISPR/Cas9 gene drives;nonrandomly mating wild populations;variable
5
J
Science & Technology - Other Topics
(ITD);BINDING;Cas9;Cas9 target sites;characteristic;characterization;CRISPR/Cas9;CRISPR/Cas9 gene drives;CRISPR/Cas9-based synthetic gene drive;crop pests;designing;disease vectors;disease-vectoring arthropods;drives will;effect;efficacy;equivalent;flour beetle Tribolium castaneum;four populations;function;genetic data;genetic variability;genome-wide analysis;immune;mating system;mild inbreeding;MUTAGENIC CHAIN-REACTION;MUTATIONS;nonrandomly mating wild populations;OFF-TARGET SITES;POPULATIONS;populations harbor genetic variants;potential;rare ITD allele;RNA-GUIDED ENDONUCLEASE;synthetic gene drives;SYSTEM;TRIBOLIUM-CASTANEUM;variable;vector;wild populations
Drury, D W
BINDING;CAS9;GENOME-WIDE ANALYSIS;MUTAGENIC CHAIN-REACTION;MUTATIONS;OFF-TARGET SITES;RNA-GUIDED ENDONUCLEASE;SYSTEM;TRIBOLIUM-CASTANEUM;VECTOR
null
[Drury, Douglas W.; Dapper, Amy L.; Siniard, Dylan J.; Zentner, Gabriel E.; Wade, Michael J.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Dapper, Amy L.] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
This work was supported by Indiana University startup funds (G.E.Z.) and NIH R01 GM084238 (M.J.W.). The sequencing was supported by an NSF Doctora lDissertation Improvement Grant (1311167 to M.J.W and A.L.D).
(ITD);Cas9 target sites;characteristic;characterization;CRISPR/Cas9;CRISPR/Cas9-based synthetic gene drive;crop pests;designing;disease vectors;disease-vectoring arthropods;drives will;effect;efficacy;equivalent;flour beetle Tribolium castaneum;four populations;function;genetic data;genetic variability;immune;mating system;mild inbreeding;populations;populations harbor genetic variants;potential;rare ITD allele;synthetic gene drives;wild populations
10.1016/j.cell.2015.09.038;10.1016/j.cell.2016.10.044;10.1016/j.gene.2005.04.025;10.1016/S0005-2736(99)00064-4;10.1038/154607a0;10.1038/nature13011;10.1038/nature14299;10.1038/nature14592;10.1038/nbt.2889;10.1038/nbt.2916;10.1038/nbt.3439;10.1038/sj.hdy.6885930;10.1038/srep00288;10.1038/srep05405;10.1046/j.1365-2540.2000.00676.x;10.1073/pnas.1521077112;10.1093/bioinformatics/btp324;10.1093/bioinformatics/btr589;10.1093/bioinformatics/btu743;10.1093/emph/eow030;10.1093/nar/gkp807;10.1093/nar/gkv137;10.1111/eva.12219;10.1111/j.1420-9101.2011.02394.x;10.1126/science.122.3163.287;10.1126/science.130.3380.902;10.1126/science.aaa5945;10.1146/annurev.ge.01.120167.000345;10.1371/journal.pone.0077904;10.1371/journal.pone.0128036;10.1534/genetics.115.177592;10.4269/ajtmh.2001.65.491;10.7554/eLife.03401
Indiana Univ
Dapper, A L;Drury, D W;Siniard, D J;Wade, M J;Zentner, G E
Drury, D W: Indiana Univ, Dept Biol, Bloomington, IN 47405 USA
null
1311167;NIH R01 GM084238
40
null
USA
Indiana Univ;Univ Wisconsin
Drury, Douglas W
Green Published, gold, Green Submitted
BINDING;CAS9;GENOME-WIDE ANALYSIS;MUTAGENIC CHAIN-REACTION;MUTATIONS;OFF-TARGET SITES;RNA-GUIDED ENDONUCLEASE;SYSTEM;TRIBOLIUM-CASTANEUM;VECTOR
Drury, Douglas W.; Dapper, Amy L.; Siniard, Dylan J.; Zentner, Gabriel E.; Wade, Michael J.;
null
Indiana Univ, Dept Biol, Bloomington, IN 47405 USA;Univ Wisconsin, Genet Lab, Madison, WI 53706 USA
Indiana Univ, Dept Biol, Bloomington, IN 47405 USA;Univ Wisconsin, Genet Lab, Madison, WI 53706 USA
null
null
5
1927;1944;1955;1959;1960;1967;1979;1987;1994;1999;2000;2001;2005;2009;2010;2011;2012;2013;2014;2015;2016;2017
78
Indiana Univ, Dept Biol, Bloomington, IN 47405 USA
Sci. Adv.
Wade, Michael J
AMER ASSOC ADVANCEMENT SCIENCE
(ITD);,;a;accentuated;allele;alter;among;and;arthropods;based;beetle;but;by;can;Cas9;castaneum;characteristic;characterization;conclude;control;CRISPR/Cas9;CRISPR/Cas9-based;crop;data;designing;disease;disease-vectoring;drive;drives;effect;efficacy;eliminate;equivalent;even;flour;four;from;function;gene;genetic;harbor;have;how;immune;in;inbreeding;is;it;ITD;many;mating;mild;most;of;on;or;pests;populations;potential;rare;reduce;render;require;show;sites;some;such;suppress;synthetic;system;target;targeted;that;the;them;they;this;to;Tribolium;unclear;using;variability;variants;vectors;we;which;wild;will;within;would
Indiana Univ
Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum, we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.
null
BINDING;CAS9;GENOME-WIDE ANALYSIS;MUTAGENIC CHAIN-REACTION;MUTATIONS;OFF-TARGET SITES;RNA-GUIDED ENDONUCLEASE;SYSTEM;TRIBOLIUM-CASTANEUM;VECTORS
3
null
null
7
BINDING;CAS9;GENOME-WIDE ANALYSIS;MUTAGENIC CHAIN-REACTION;MUTATIONS;OFF-TARGET SITES;RNA-GUIDED ENDONUCLEASE;SYSTEM;Tribolium castaneum;VECTORS
WOS:000401955300006
Indiana Univ, Bloomington, IN USA;Univ Wisconsin, Madison, WI USA
USA
2,017
null
0000-0002-0801-7646
null
null
English
null
AM J TROP MED HYG;ANNU REV GENET;BBA-BIOMEMBRANES;BIOINFORMATICS;CELL;CR SOC BIOL;ELEMENTS EVOLUTIONAR;ELIFE;EVOL APPL;EVOL MED PUBLIC HLTH;GENE;GENETICS;HEREDITY;J EVOLUTION BIOL;NAT BIOTECHNOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;Phytochemical Bulletin;PLOS ONE;QUANT BIOL;SCI REP-UK;SCIENCE
Dapper, Amy L;Drury, Douglas W;Siniard, Dylan J;Wade, Michael J;Zentner, Gabriel E
2024-03-11 ER
Baym, M;Bull, J J;Bushland, R C;Chan, S W;Charlesworth B.;Dobrovolskaïa-Zavadskaïa, N;Donnelly, M J;Doyle J.J.;Drury, D W;Esvelt, K M;Gantz, V M;Hammond, A;Hiraizumi, Y;Kim, H S;Kleinstiver, B P;Knipling, E F;Kofler, R;Komor, A C;Krstic, D;Kuscu, C;Lewontin R. C.;Li, H;Lu, Y H;Mackenzie, S M;Naito, Y;O'Geen, H;Ran, F A;Robert, M A;Sternberg, S H;Turner, B C;Unckless, R L;Urbanelli, S;Vanderplank, F L;Vazeille, M;Wade, M J;Wu Xuebing;Wu, X B;Zetsche, B;Zhang, Y L
EV7KW
Bloomington, IN USA
84
null
2
null
28,560,324
Dapper, Amy L;Drury, Douglas W;Siniard, Dylan J;Wade, Michael J;Zentner, Gabriel E
SCI ADV
Bloomington, IN USA;Madison, WI USA
Andrews, B;Boone, C;Costanzo, M;Myers, C L;Tan, Y Z;Usaj, M;VanderSluis, B;Wang, W;Zou, A
10.1534/g3.117.040220
null
9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
5bl63371g2rl5v5p1e5p15f37g3j58q4o2
TheCellMap. org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network
Univ Toronto
null
Costanzo, M; Andrews, B; Boone, C (corresponding author), Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada.;Myers, CL (corresponding author), Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA.
null
Andrews, Brenda;Boone, Charles;Costanzo, Michael;Myers, Chad L;Tan, Yizhao;Usaj, Matej;VanderSluis, Benjamin;Wang, Wen;Zou, Albert
Genetics & Heredity
National Institutes of Health [R01HG005853, R01HG005084]; Canadian Institutes of Health Research [FDN-143264, FDN-143265]; National Science Foundation [DBI\0953881]; Direct For Biological Sciences; Div Of Biological Infrastructure [0953881] Funding Source: National Science Foundation
WOS
Andrews, B;Boone, C;Costanzo, M;Myers, C L
Princeton Univ, Princeton, NJ USA;Simons Fdn, New York, NY USA;Univ Minnesota Twin Cities, Minneapolis, MN USA;Univ Toronto, Toronto ON, Canada
7
:;a;and;Database;for;genetic;Global;Interaction;Mining;network;org;the;theCellMap;Visualizing;Web-Accessible;yeast
2
Usaj, Matej;Wang, Wen
GENETICS SOCIETY AMERICA
B; Boone, C (corresponding author), Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada.; Myers, CL (corresponding author), Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA;Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA;Simons Fdn, Simons Ctr Data Anal, New York, NY 10010 USA;Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA;Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada;Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada
Article
Univ Minnesota Twin Cities;Univ Toronto
BETHESDA
null
null
Princeton Univ;Simons Fdn;Univ Minnesota Twin Cities;Univ Toronto
Canadian Institutes of Health Research;Direct For Biological Sciences;Div Of Biological Infrastructure;National Institutes of Health;National Science Foundation
Costanzo, M; Andrews, B; Boone, C (corresponding author), Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada.; Myers, CL (corresponding author), Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA.
1549
Andrews, Brenda;Boone, Charles;Costanzo, Michael;Myers, Chad L;Tan, Yizhao;Usaj, Matej;VanderSluis, Benjamin;Wang, Wen;Zou, Albert
6
5
400,822,200,014
Canadian Institutes of Health Research [FDN-143264, FDN-143265];Direct For Biological Sciences;Div Of Biological Infrastructure [0953881] Funding Source: National Science Foundation;National Institutes of Health [R01HG005853, R01HG005084];National Science Foundation [DBI\0953881]
Canada;USA
G3-GENES GENOMES GENETICS
Canada;USA
null
null
Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada
2160-1836
Andrews, B;Boone, C;Costanzo, M;Myers, C L;Tan, Y Z;Usaj, M;VanderSluis, B;Wang, W;Zou, A
MAY
brenda.andrews@utoronto.ca;charlie.boone@utoronto.ca;cmyers@cs.umn.edu;michael.costanzo@utoronto.ca
Global Yeast Genetic Interaction Network;org;theCellMap;Web-Accessible Database
9
J
Genetics & Heredity
access;ANNOTATION ERRORS;budding yeast Saccharomyces cerevisiae;cell;central repository;data-driven network layouts;deletion;genetic interactions;genetic network;genome-scale Synthetic Genetic Array (SGA) experiments;Global Yeast Genetic Interaction Network;INTERACTION MAP;interactive manner;key;large-scale data validation;localization;MISSING HERITABILITY;mutants;new discoveries;ONTOLOGY;org;org serves;providing access;quantitative genetic interaction data;quantitative genomic data;SACCHAROMYCES-CEREVISIAE GENOME;storing;subnetworks;synthetic genetic array SGA;systematic Identification;theCellMap;users;Web-Accessible Database;yeast genetics
Usaj, M
ANNOTATION ERRORS;CELL;DELETION;genetic interactions;genetic network;INTERACTION MAP;LOCALIZATION;MISSING HERITABILITY;MUTANTS;ONTOLOGY;SACCHAROMYCES-CEREVISIAE GENOME;synthetic genetic array SGA;SYSTEMATIC IDENTIFICATION;yeast genetics
1539
[Usaj, Matej; Tan, Yizhao; Zou, Albert; Costanzo, Michael; Andrews, Brenda; Boone, Charles] Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada. [Andrews, Brenda; Boone, Charles] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada. [Wang, Wen; VanderSluis, Benjamin; Myers, Chad L.] Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA. [VanderSluis, Benjamin] Simons Fdn, Simons Ctr Data Anal, New York, NY 10010 USA. [VanderSluis, Benjamin] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
We thank A. Baryshnikova, D. Botstein, and members of the Andrews, Boone, and Myers labs for helpful discussions and critical comments. This work was supported by the National Institutes of Health (R01HG005853 to C.B., B.A., and C.L.M., and R01HG005084 to C.L.M.), the Canadian Institutes of Health Research (FDN-143264 and FDN-143265 to C.B. and B.A.), and the National Science Foundation (DBI\0953881 to C.L.M.). B.A., C.B., and C.L.M. are Senior Fellows in the Genetic Networks program of the Canadian Institute for Advanced Research, and C.B. is co-Director of the Program.
access;budding yeast Saccharomyces cerevisiae;central repository;data-driven network layouts;genetic interactions;genome-scale Synthetic Genetic Array (SGA) experiments;interactive manner;key;large-scale data validation;new discoveries;org;org serves;providing access;quantitative genetic interaction data;quantitative genomic data;storing;subnetworks;theCellMap;users
10.1007/978-1-4939-1363-3_10;10.1016/0092-8674(85)90154-0;10.1016/j.cels.2016.04.014;10.1016/j.copbio.2010.11.001;10.1038/75556;10.1038/msb.2013.54;10.1038/nature00935;10.1038/nature02026;10.1038/nature11867;10.1038/ncomms9712;10.1038/NMETH.1534;10.1073/pnas.0712255105;10.1073/pnas.1119675109;10.1093/nar/gkh036;10.1093/nar/gkv1284;10.1126/science.1065810;10.1126/science.1180823;10.1126/science.285.5429.901;10.1126/science.291.5506.1001;10.1126/science.aaf1420;10.1242/jcs.00611;10.1534/g3.115.017830;[10.1038/nmeth.1890, 10.1038/NMETH.1890]
Univ Toronto
Andrews, B;Boone, C;Costanzo, M;Myers, C L;Tan, Y Z;Usaj, M;VanderSluis, B;Wang, W;Zou, A
Usaj, M: Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada
Usaj, Matej;Wang, Wen;Boone, Charles
0953881;DBI\0953881;FDN-143264;FDN-143265;R01HG005084;R01HG005853
25
null
Canada
Princeton Univ;Simons Fdn;Univ Minnesota Twin Cities;Univ Toronto
Usaj, Matej
Green Published, gold
ANNOTATION ERRORS;CELL;DELETION;INTERACTION MAP;LOCALIZATION;MISSING HERITABILITY;MUTANTS;ONTOLOGY;SACCHAROMYCES-CEREVISIAE GENOME;SYSTEMATIC IDENTIFICATION
Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L.; Costanzo, Michael; Andrews, Brenda; Boone, Charles;
null
Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA;Simons Fdn, Simons Ctr Data Anal, New York, NY 10010 USA;Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA;Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada;Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada
Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA;Simons Fdn, Simons Ctr Data Anal, New York, NY 10010 USA;Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA;Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada;Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada
null
genetic interaction;Genetic networks;Synthetic genetic array (SGA);yeast genetics
5
1985;1999;2000;2001;2002;2003;2004;2008;2010;2011;2012;2013;2014;2015;2016
78
Univ Minnesota Twin Cities, Dept Comp Sci & Engn, 200 Union St, Minneapolis, MN 55455 USA;Univ Toronto, Donnelly Ctr, 160 Coll St,Room 13212, Toronto, ON M5S 3E1, Canada
G3-Genes Genomes Genet.
Boone, Charles
GENETICS SOCIETY AMERICA
(SGA);,;a;access;allows;an;analyzing;and;annotate;array;as;budding;by;central;cerevisiae;data;data-driven;discoveries;easily;ensure;experiments;explore;extract;for;functionally;genetic;genome-scale;genomic;in;interaction;interactions;interactive;intuitive;is;key;large-scale;layouts;manner;network;new;or;org;particular;produced;promote;providing;quantitative;reorganize;repository;Saccharomyces;serves;storing;subnetworks;synthetic;the;theCellMap;to;users;using;validation;visualize;with;yeast
Univ Minnesota Twin Cities;Univ Toronto
Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap. org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae. In particular, TheCellMap. org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner.
E-6320-2012;IQX-0075-2023;J-5454-2015
ANNOTATION ERRORS;CELLS;DELETION;INTERACTION MAP;LOCALIZATION;MISSING HERITABILITY;MUTANTS;ONTOLOGY;SACCHAROMYCES-CEREVISIAE GENOME;SYSTEMATIC IDENTIFICATION
0
null
genetic interactions;genetic network;synthetic genetic array SGA;yeast genetics
11
ANNOTATION ERRORS;CELLS;DELETION;genetic interactions;Genetic networks;INTERACTION MAP;LOCALIZATION;MISSING HERITABILITY;MUTANTS;ONTOLOGY;SACCHAROMYCES-CEREVISIAE GENOME;Synthetic genetic array (SGA);SYSTEMATIC IDENTIFICATION;yeast genetics
WOS:000400822200014
Princeton Univ, Princeton, NJ USA;Simons Fdn, New York, NY USA;Univ Minnesota Twin Cities, Minneapolis, MN USA;Univ Toronto, Toronto ON, Canada
Canada;USA
2,017
null
0000-0002-5812-6744;0000-0003-0675-2847
null
null
English
null
CELL;CELL SYST;CURR OPIN BIOTECH;Epistasis and the Evolutionary Process;J CELL SCI;METHODS MOL BIOL;MOL SYST BIOL;NAT COMMUN;NAT GENET;NAT METHODS;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;SCIENCE;SPRING EMBEDDERS FOR
Andrews, Brenda;Boone, Charles;Costanzo, Michael;Myers, Chad L;Tan, Yizhao;Usaj, Matej;VanderSluis, Benjamin;Wang, Wen;Zou, Albert
2024-03-11 ER
Ashburner, M;Atias, N;Baryshnikova, A;Ben-Shitrit, T;Bloom, J S;Costanzo, M;Evangelista, M;Giaever, G;Harris, M A;Hartman, J L;Huh, W K;Kobourov S. G.;Koh, J L Y;Kuzmin, E;Mani, R;Novick, P;Phillips Pc.;Tong, A H Y;Vizeacoumar, F J;Winzeler, E A;Zuk, O
EU1YN
Minneapolis, MN USA;Toronto ON, Canada.
95
null
4
null
28,325,812
Andrews, Brenda;Boone, Charles;Costanzo, Michael;Myers, Chad L;Tan, Yizhao;Usaj, Matej;VanderSluis, Benjamin;Wang, Wen;Zou, Albert
G3-GENES GENOM GENET
Minneapolis, MN USA;New York, NY USA;Princeton, NJ USA;Toronto ON, Canada
Arangundy-Franklin, S;Holliger, P;Houlihan, G
10.1021/acs.accounts.7b00056
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
31s4m1a10681um4i3a3q2m1q2l70121f3t6j4z
Exploring the Chemistry of Genetic Information Storage and Propagation through Polymerase Engineering
MRC
null
Holliger, P (corresponding author), MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
null
Arangundy-Franklin, Sebastian;Holliger, Philipp;Houlihan, Gillian
Chemistry, Multidisciplinary
Medical Research Council [MC_U105178804]; MRC-AstraZeneca/MedImmune Blue Sky Grant; MRC [MC_U105178804] Funding Source: UKRI; Medical Research Council [MC_U105178804] Funding Source: researchfish
WOS
Holliger, P
MRC, Cambridge, England
50
and;chemistry;engineering;exploring;genetic;Information;of;polymerase;Propagation;Storage;the;through
1
Holliger, Philipp
AMER CHEMICAL SOC
MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
Review
MRC
WASHINGTON
null
null
Lab Mol Biol;MRC
Medical Research Council;MRC;MRC-AstraZeneca/MedImmune Blue Sky Grant
Holliger, P (corresponding author), MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
1087
Arangundy-Franklin, Sebastian;Holliger, Philipp;Houlihan, Gillian
46
1
399,859,800,045
Medical Research Council [MC_U105178804];Medical Research Council [MC_U105178804] Funding Source: researchfish;MRC [MC_U105178804] Funding Source: UKRI;MRC-AstraZeneca/MedImmune Blue Sky Grant
UK
ACCOUNTS OF CHEMICAL RESEARCH
UK
null
null
MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
0001-4842
Arangundy-Franklin, S;Holliger, P;Houlihan, G
APR
phl@mrc-lmb.cam.ac.uk
Chemistry;Genetic Information Storage;Polymerase Engineering;Propagation
3
J
Chemistry
3D folding;ability;analysis;applications;area will;backbone linkages;basic level;biological information;biopolymers;biotechnology;carriers;catalysis;catalysts;CHEMICAL ETIOLOGY;chemical parameter range;CHEMISTRY;chemists;CONSPECTUS;decoding information;degree;described;determination;devices;different chemistries;directed evolution;distinct form;DNA;DNA-POLYMERASE;en-;encoding genetic information;engineering;enzymatic synthesis;ENZYMATIC-SYNTHESIS;established DNA designs;evolution;exploration;fidelity;first tentative forays;function;fundamental property;genetic information;genetic information (molecular heredity);Genetic Information Storage;Goldilocks;good efficiency;high throughput plate-based screens;ideal;inception;information transfer;investigation;large (if finite) number;lead;leads;least;life;ligands (aptamers);medicine;molecular embodiment;molecular heredity;molecular parameters;nanostructures;natural nucleic acids DNA;natural polymerases;nature;non-cognate nucleotide substrates;non-enzymatic synthesis;novel sequence spaces;novel strategies;nucleic acids;NUCLEIC-ACIDS;nucleobases;number;origin;panoply;phage display;phenotypic space;Polymerase Engineering;polymerase enzymes;polymerase function;polymerases;polymers;polypeptides;polysaccharides;potential;powerful method;progress;PROPAGATION;providing access;question;questions;range;realized;related nucleic acids;replication;repositories;reverse;REVERSE-TRANSCRIPTASE ACTIVITY;rich sequence;RNA;RNA-POLYMERASE;screening;SELECTION;sequence-defined biopolymer;several catalysts;simple polyhedron nanostructures;spaces;store;structure;synthetic genetic polymers;synthetic genetics;synthetic nucleic acids comprising unnatural sugar ring congeners;SYSTEM;TARGETS;TNA;two;unique capacity;variation;water-in-oil emulsion technology based methods;will;yield novel ligands
Houlihan, G
CHEMICAL ETIOLOGY;directed evolution;DNA-POLYMERASE;ENZYMATIC-SYNTHESIS;NUCLEIC-ACIDS;REVERSE-TRANSCRIPTASE ACTIVITY;RNA-POLYMERASE;SELECTION;SYSTEM;TNA
1079
[Houlihan, Gillian; Arangundy-Franklin, Sebastian; Holliger, Philipp] MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
The authors acknowledge support by the Medical Research Council (G.H. and P.H., program no. MC_U105178804) and an MRC-AstraZeneca/MedImmune Blue Sky Grant supporting the salary of S.A.-F.
3D folding;ability;analysis;applications;area will;backbone linkages;basic level;biological information;biopolymers;biotechnology;carriers;catalysis;catalysts;chemical parameter range;chemistry;chemists;CONSPECTUS;decoding information;degree;described;determination;devices;different chemistries;distinct form;DNA;en-;encoding genetic information;engineering;enzymatic synthesis;established DNA designs;evolution;exploration;fidelity;first tentative forays;function;fundamental property;genetic information;genetic information (molecular heredity);Goldilocks;good efficiency;high throughput plate-based screens;ideal;inception;information transfer;investigation;large (if finite) number;lead;leads;least;life;ligands (aptamers);medicine;molecular embodiment;molecular heredity;molecular parameters;nanostructures;natural nucleic acids DNA;natural polymerases;nature;non-cognate nucleotide substrates;non-enzymatic synthesis;novel sequence spaces;novel strategies;nucleic acids;nucleobases;number;origin;panoply;phage display;phenotypic space;polymerase enzymes;polymerase function;polymerases;polymers;polypeptides;polysaccharides;potential;powerful method;progress;providing access;question;questions;range;realized;related nucleic acids;replication;repositories;reverse;rich sequence;RNA;screening;sequence-defined biopolymer;several catalysts;simple polyhedron nanostructures;spaces;store;structure;synthetic genetic polymers;synthetic genetics;synthetic nucleic acids comprising unnatural sugar ring congeners;targets;two;unique capacity;variation;water-in-oil emulsion technology based methods;will;yield novel ligands
10.1002/(SICI)1521-3773(19990419)38:8<1124::AID-ANIE1124>3.0.CO;2-W;10.1002/1521-3773(20021004)41:19<3620::AID-ANIE3620>3.0.CO;2-C;10.1002/anie.200500047;10.1002/anie.200601217;10.1002/anie.200602772;10.1002/anie.200900953;10.1002/anie.201503652;10.1002/anie.201508678;10.1002/anie.201604641;10.1002/cbic.201000384;10.1002/cbic.201600136;10.1007/978-1-4939-3197-2_4;10.1016/0022-2836(84)90425-X;10.1016/0968-0004(89)90130-8;10.1016/j.jbiotec.2013.07.005;10.1016/j.jmb.2006.06.050;10.1021/ar040004z;10.1021/bi400558c;10.1021/ja035917n;10.1021/ja038525p;10.1021/ja0428255;10.1021/ja045364w;10.1021/ja053322h;10.1021/ja3017889;10.1021/ja9039696;10.1021/ja909180c;10.1021/jp3056834;10.1038/nature12306;10.1038/nature13314;10.1038/nature13982;10.1038/nature21022;10.1038/nbt.2556;10.1038/nbt1321;10.1038/nbt974;10.1038/ncomms11235;10.1039/c2cc35028a;10.1039/c5ob01540e;10.1073/pnas.071052198;10.1073/pnas.1013804107;10.1073/pnas.1120964109;10.1073/pnas.1133470100;10.1073/pnas.1213933109;10.1073/pnas.1319590110;10.1073/pnas.93.18.9670;10.1073/pnas.95.7.3402;10.1073/pnas.96.17.9491;10.1073/pnas.97.10.5095;10.1073/pnas.97.8.3868;10.1074/jbc.M005757200;10.1074/jbc.M113.532697;10.1093/nar/30.2.605;10.1093/nar/gki840;10.1093/nar/gkq1053;10.1093/nar/gkq1360;10.1093/nar/gkr1068;10.1093/nar/gkv1057;10.1093/nar/gkv1472;10.1093/nar/gkv798;10.1093/nar/gkw812;10.1093/protein/gzw052;10.1101/cshperspect.a023770;10.1126/science.1200752;10.1126/science.1217622;10.1126/science.1241888;10.1126/science.2434996;10.1126/science.284.5423.2118;10.1126/science.286.5438.295;10.1126/science.290.5495.1347;10.1126/science.aaf5409;10.1186/1759-2208-3-2];[10.1038/NCHEM.1241, 10.1038/nchem.1241];[10.1038/NCHEM.2493, 10.1038/nchem.2493];[10.1038/NCHEMBIO.280, 10.1038/nchembio.280];[10.1038/NCHEMBIO.966, 10.1038/nchembio.966]
MRC
Arangundy-Franklin, S;Holliger, P;Houlihan, G
Houlihan, G: MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
Houlihan, Gillian
MC_U105178804
77
null
UK
MRC
Houlihan, Gillian
Green Published, hybrid
CHEMICAL ETIOLOGY;DIRECTED EVOLUTION;DNA-POLYMERASE;ENZYMATIC-SYNTHESIS;NUCLEIC-ACIDS;REVERSE-TRANSCRIPTASE ACTIVITY;RNA-POLYMERASE;SELECTION;SYSTEM;TNA
Houlihan, Gillian; Arangundy-Franklin, Sebastian; Holliger, Philipp;
null
MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
1520-4898
null
4
1984;1987;1989;1996;1998;1999;2000;2001;2002;2003;2004;2005;2006;2007;2009;2010;2011;2012;2013;2014;2015;2016;2017
53
MRC, Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England
Accounts Chem. Res.
Holliger, Philipp
AMER CHEMICAL SOC
";(aptamers);(if;(molecular;,;3D;:;a;ability;access;acids;address;against;although;an;analysis;and;anticipate;apart;applications;are;area;as;at;backbone;based;basic;be;been;biological;biopolymer;biopolymers;biotechnology;but;can;capacity;carriers;catalysis;catalysts;chemical;chemistries;chemistry;chemists;closely;compatible;comprising;congeners;CONSPECTUS;created;currently;decoding;deeper;degree;demonstrates;described;designs;determination;devices;different;directed;discuss;display;distinct;DNA;efficiency;efficiently;efforts;elaborated;embodiment;emergence;emulsion;en-;encode;encoding;endow;engineered;engineering;enzymatic;enzymes;establish;established;establishing;evolution;evolved;expand;exploration;fidelity;finally;finite);first;folding;for;forays;form;found;from;function;fundamental;further;genetic;genetics;Goldilocks;good;has;have;here;heredity;heredity);high;ideal;illuminate;in;inception;increasingly;information;investigation;is;it;its;just;large;largely;lead;leads;least;level;life;ligands;linkages;may;means;medicine;method;methods;molecular;nanostructures;natural;naturally;nature;non-cognate;non-enzymatic;not;novel;nucleic;nucleobases;nucleotide;number;of;opened;or;order;origin;other;panoply;parameter;parameters;phage;phenotypic;plate-based;polyhedron;polymerase;polymerases;polymers;polypeptides;polysaccharides;potential;powerful;progress;propagate;property;providing;question;questions;range;realized;regarding;related;remains;replicated;replication;repositories;requires;restricted;reverse;rich;ring;RNA;screening;screens;seemingly;sequence;sequence-defined;sets;several;short;simple;some;space;spaces;still;store;strategies;structure;substrates;such;sugar;synthesis;synthesize;synthesized;synthetic;taking;targets;technology;tentative;that;the;their;them;therefore;these;they;this;through;throughput;to;toward;transcribe;transfer;two;unexplored;unique;unnatural;up;utilize;variation;water-in-oil;we;what;which;while;will;with;would;yield;yielded
MRC
CONSPECTUS: Nucleic acids are a distinct form of sequence-defined biopolymer. What sets them apart from other biopolymers such as polypeptides or polysaccharides is their unique capacity to encode, store, and propagate genetic information (molecular heredity). In nature, just two closely related nucleic acids, DNA and RNA, function as repositories and carriers of genetic information. They therefore are the molecular embodiment of biological information. This naturally leads to questions regarding the degree of variation from this seemingly ideal "Goldilocks" chemistry that would still be compatible with the fundamental property of molecular heredity. To address this question, chemists have created a panoply of synthetic nucleic acids comprising unnatural sugar ring congeners, backbone linkages, and nucleobases in order to establish the molecular parameters for encoding genetic information and its emergence at the origin of life. A deeper analysis of the potential of these synthetic genetic polymers for molecular heredity requires a means of replication and a determination of the fidelity of information transfer. While non-enzymatic synthesis is an increasingly powerful method, it currently remains restricted to short polymers. Here we discuss efforts toward establishing enzymatic synthesis, replication, and evolution of synthetic genetic polymers through the engineering of polymerase enzymes found in nature. To endow natural polymerases with the ability to efficiently utilize non-cognate nucleotide substrates, novel strategies for the screening and directed evolution of polymerase function have been realized. High throughput plate-based screens, phage display, and water-in-oil emulsion technology based methods have yielded a number of engineered polymerases, some of which can synthesize and reverse transcribe synthetic genetic polymers with good efficiency and fidelity. The inception of such polymerases demonstrates that, at a basic level at least, molecular heredity is not restricted to the natural nucleic acids DNA and RNA, but may be found in a large (if finite) number of synthetic genetic polymers. And it has opened up these novel sequence spaces for investigation. Although largely unexplored, first tentative forays have yielded ligands (aptamers) against a range of targets and several catalysts elaborated in a range of different chemistries. Finally, taking the lead from established DNA designs, simple polyhedron nanostructures have been described. We anticipate that further progress in this area will expand the range of synthetic genetic polymers that can be synthesized, replicated, and evolved providing access to a rich sequence, structure, and phenotypic space. "Synthetic genetics", that is, the exploration of these spaces, will illuminate the chemical parameter range for en- and decoding information, 3D folding, and catalysis and yield novel ligands, catalysts, and nanostructures and devices for applications in biotechnology and medicine.
Y-6197-2019
CHEMICAL ETIOLOGY;DIRECTED EVOLUTION;DNA-POLYMERASE;ENZYMATIC-SYNTHESIS;NUCLEIC-ACIDS;REVERSE-TRANSCRIPTASE ACTIVITY;RNA-POLYMERASE;SELECTION;SYSTEM;TNA
1
null
null
9
CHEMICAL ETIOLOGY;directed evolution;DNA-POLYMERASE;ENZYMATIC-SYNTHESIS;NUCLEIC-ACIDS;REVERSE-TRANSCRIPTASE ACTIVITY;RNA-POLYMERASE;SELECTION;SYSTEM;TNA
WOS:000399859800045
MRC, Cambridge, England
UK
2,017
null
0000-0002-3440-9854
null
null
English
null
ACCOUNTS CHEM RES;ANGEW CHEM INT EDIT;BIOCHEMISTRY-US;CHEM COMMUN;CHEMBIOCHEM;CSH PERSPECT BIOL;CURR PROTOC NUCL ACI;J AM CHEM SOC;J BIOL CHEM;J BIOTECHNOL;J MOL BIOL;J PHYS CHEM B;J SYST CHEM;METHODS MOL BIOL;NAT BIOTECHNOL;NAT CHEM;NAT CHEM BIOL;NAT COMMUN;NATURE;NUCLEIC ACIDS RES;ORG BIOMOL CHEM;P NATL ACAD SCI USA;POLYM ENG PCR SEQUEN;PROTEIN ENG DES SEL;SCIENCE;TRENDS BIOCHEM SCI
Arangundy-Franklin, Sebastian;Holliger, Philipp;Houlihan, Gillian
2024-03-11 ER
Ablasser, A;Adamala, K;Anosova, I;Arezi B.;Astatke, M;Baar, C;Benner, S A;Bergen, K;Betz, K;Brudno, Y;Chaput, J C;Chen, T J;Cozens, C;D'Abbadie, M;Davies, D R;Dressman, D;Eckstein, F;Ellefson, J W;Eschenmoser, A;Fa, M;Ferreira-Bravo, I A;Gardner, A F;Gelinas, A D;Ghadessy, F J;Hansen, C J;Hollenstein, M;Horhota, A;Huber, C;Ibach, J;Ichida, J K;Jestin, J L;Joyce, G F;Kimoto, M;Kranaster, R;Laos, R;Larsen, A C;Leconte, A M;Li, Y;Loakes, D;Lockless, S W;Lou, D I;Malyshev, D A;Mauer, J;Millar, D;Nelson, K E;Obeid, S;Ong, J L;Patel, P H;Pinheiro V. B.;Pinheiro, V B;Povilaitis, T;Ramsay, N;Sauter, K B M;Schöning, K U;Siegmund, V;Smith, D A;Staiger, N;Summerer, D;Suzuki, M;Szostak J. W.;Taylor, A I;Tolle, F;Vichier-Guerre, S;Welter, M;Westheimer, F H;Wochner, A;Yamashige, R;Yu, H Y
ES9EV
Cambridge, England
60
null
1
null
28,383,245
Arangundy-Franklin, Sebastian;Holliger, Philipp;Houlihan, Gillian
ACCOUNTS CHEM RES
Cambridge, England
Izuhara-Kihara, H;Matoba, Y;Noda, M;Sugiyama, M;Yoshida, T
10.1002/pro.3123
null
111 RIVER ST, HOBOKEN 07030-5774, NJ USA
294h623m4o1w6ro292b3hg113u615m2w2c6u
Crystallographic and mutational analyses of cystathionine β-synthase in the H<sub>2</sub>S-synthetic gene cluster in <i>Lactobacillus plantarum</i>
Hiroshima Univ
null
Matoba, Y (corresponding author), Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Microbiol, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan.;Sugiyama, M (corresponding author), Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Probiot Sci Prevent Med, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan.
null
Izuhara-Kihara, Hisae;Matoba, Yasuyuki;Noda, Masafumi;Sugiyama, Masanori;Yoshida, Tomoki
Biochemistry & Molecular Biology
Japan Society for the Promotion of Science [15K07997]; Grants-in-Aid for Scientific Research [15K07997, 15H00947] Funding Source: KAKEN
WOS
Matoba, Y;Sugiyama, M
Hiroshima Univ, Hiroshima, Japan
26
<i>Lactobacillus;analyses;and;Cluster;crystallographic;cystathionine;gene;H<sub>2</sub>S-synthetic;in;mutational;of;plantarum</i>;the;β-synthase
1
null
WILEY
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Microbiol, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan.; Sugiyama, M (corresponding author), Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Probiot Sci Prevent Med, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan;Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan
Article
Hiroshima Univ
HOBOKEN
null
null
Hiroshima Univ
Grants-in-Aid for Scientific Research;Japan Society for the Promotion of Science
Matoba, Y (corresponding author), Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Microbiol, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan.; Sugiyama, M (corresponding author), Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Probiot Sci Prevent Med, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan.
783
Izuhara-Kihara, Hisae;Matoba, Yasuyuki;Noda, Masafumi;Sugiyama, Masanori;Yoshida, Tomoki
10
1
398,183,800,011
Grants-in-Aid for Scientific Research [15K07997, 15H00947] Funding Source: KAKEN;Japan Society for the Promotion of Science [15K07997]
Japan
PROTEIN SCIENCE
Japan
null
null
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan
0961-8368
Izuhara-Kihara, H;Matoba, Y;Noda, M;Sugiyama, M;Yoshida, T
APR
sugi@hiroshima-u.ac.jp;ymatoba@hiroshima-u.ac.jp
<i>Lactobacillus plantarum</i>;crystallographic;cystathionine β-synthase;H<sub>2</sub>S-synthetic gene cluster;mutational analyses
5
J
Biochemistry & Molecular Biology
-ketobutylic acid;<i>Lactobacillus plantarum</i>;ACTIVE-SITE;Ala70;ALPHA-AMINOACRYLATE INTERMEDIATE;amino acid;amino acid sequence;AMINO-ACIDS;ammonia;antibiotics;BACTERIA;CBS;CBS-;CGL;CGL-encoding genes;CLUSTER;crystal structure;CRYSTAL-STRUCTURES;crystallographic;cystathionine -lyase (CGL);cystathionine beta-synthase;cystathionine beta-synthase (CBS);cystathionine β-synthase;enzymatic ability;enzymatic properties;enzymes;ESCHERICHIA-COLI;eukaryotic CBS;eukaryotic cells;first substrate;formation;genomes;Glu223 residues;H2S;H2S production;H2S suppression;H2S-generating activity;H<sub>2</sub>S-synthetic gene cluster;high affinity;hydrogen sulfide;hydrogen sulfide (H2S);inactivation;l-cystathionine;l-cysteine;l-cysteine-dependent CBS activities;l-homocysteine;l-OAS-;l-serine;L. plantarum CBS;LACTIC-ACID BACTERIA;Lactobacillus plantarum;major physiological enzymes;mutational analyses;O-acetyl-l-serine (l-OAS);O-acetyl-l-serine sulfhydrylase (OASS);O-ACETYLSERINE SULFHYDRYLASE;OASS activity;plant-derived lactic acid bacterium Lactobacillus plantarum;present study;REACTION SPECIFICITY;resulting l-cystathionine;reverse transsulfuration pathway;SALMONELLA-TYPHIMURIUM LT-2;second substrate;similarity;STRUCTURAL-BASIS;substrate binding pocket;susceptibility;tendency
Matoba, Y
ACTIVE-SITE;ALPHA-AMINOACRYLATE INTERMEDIATE;amino acid;AMINO-ACIDS;crystal structure;CRYSTAL-STRUCTURES;cystathionine beta-synthase;ESCHERICHIA-COLI;hydrogen sulfide;LACTIC-ACID BACTERIA;Lactobacillus plantarum;O-ACETYLSERINE SULFHYDRYLASE;REACTION SPECIFICITY;SALMONELLA-TYPHIMURIUM LT-2;STRUCTURAL-BASIS
763
[Matoba, Yasuyuki; Yoshida, Tomoki; Izuhara-Kihara, Hisae; Noda, Masafumi; Sugiyama, Masanori] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan.
Grant sponsor: Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science; Grant number: 15K07997.
-ketobutylic acid;Ala70;amino acid sequence;ammonia;antibiotics;bacteria;CBS;CBS-;CGL;CGL-encoding genes;cluster;crystallographic;cystathionine -lyase (CGL);cystathionine beta-synthase (CBS);enzymatic ability;enzymatic properties;enzymes;eukaryotic CBS;eukaryotic cells;first substrate;formation;genomes;Glu223 residues;H2S;H2S production;H2S suppression;H2S-generating activity;high affinity;hydrogen sulfide (H2S);inactivation;l-cystathionine;l-cysteine;l-cysteine-dependent CBS activities;l-homocysteine;l-OAS-;l-serine;L. plantarum CBS;major physiological enzymes;mutational analyses;O-acetyl-l-serine (l-OAS);O-acetyl-l-serine sulfhydrylase (OASS);OASS activity;plant-derived lactic acid bacterium Lactobacillus plantarum;present study;resulting l-cystathionine;reverse transsulfuration pathway;second substrate;similarity;substrate binding pocket;susceptibility;tendency
10.1002/yea.320100306;10.1006/jmbi.1993.1489;10.1006/jmbi.1999.3002;10.1007/s10545-006-0106-5;10.1016/0003-2697(75)90213-4;10.1016/0003-2697(92)90590-4;10.1016/0005-2744(70)90255-X;10.1016/j.abb.2004.08.024;10.1016/j.abb.2004.09.037;10.1016/j.bbapap.2011.03.006;10.1016/j.bbapap.2011.04.011;10.1016/j.febslet.2008.12.019;10.1016/S0076-6879(97)76066-X;10.1016/S0969-2126(00)00085-X;10.1021/bi00038a008;10.1021/bi00076a017;10.1021/bi00123a013;10.1021/bi035496m;10.1021/bi050485+;10.1021/bi100473v;10.1021/bi1010893;10.1021/bi952938o;10.1038/355472a0;10.1038/nrd2425;10.1073/pnas.1011448107;10.1073/pnas.1313683110;10.1073/pnas.1414545111;10.1073/pnas.85.8.2444;10.1074/jbc.C000056200;10.1074/jbc.M109.010868;10.1074/jbc.M112.414722;10.1074/jbc.M114.610782;10.1074/jbc.M505313200;10.1074/jbc.M703518200;10.1074/jbc.M805459200;10.1074/jbc.R400001200;10.1074/jbc.R400005200;10.1093/nar/25.24.4876;10.1107/s0907444994003112;10.1107/s0907444998003254;10.1126/science.1209855;10.1128/AEM.00150-08;10.1128/JB.01273-06;10.1128/JB.01372-09;10.1248/bpb.33.289;10.1271/bbb.64.1628;10.1371/journal.pone.0030696;10.1515/BC.2003.043;[10.1139/O09-003, 10.1139/o09-003]
Hiroshima Univ
Izuhara-Kihara, H;Matoba, Y;Noda, M;Sugiyama, M;Yoshida, T
Matoba, Y: Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan
null
15H00947;15K07997
52
null
Japan
Hiroshima Univ
Matoba, Yasuyuki
Bronze, Green Published
ACTIVE-SITE;ALPHA-AMINOACRYLATE INTERMEDIATE;AMINO-ACIDS;CRYSTAL-STRUCTURES;ESCHERICHIA-COLI;LACTIC-ACID BACTERIA;O-ACETYLSERINE SULFHYDRYLASE;REACTION SPECIFICITY;SALMONELLA-TYPHIMURIUM LT-2;STRUCTURAL-BASIS
Matoba, Yasuyuki; Yoshida, Tomoki; Izuhara-Kihara, Hisae; Noda, Masafumi; Sugiyama, Masanori;
null
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan
1469-896X
Amino acids;crystal structure;cystathionine beta-synthase;hydrogen sulfide;Lactobacillus plantarum
4
1966;1970;1975;1976;1988;1992;1993;1994;1995;1996;1997;1998;1999;2000;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014
17
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Microbiol, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan;Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Probiot Sci Prevent Med, Minami Ku, Kasumi 1-2-3, Hiroshima 7348551, Japan
Protein Sci.
Sugiyama, Masanori
WILEY
(CBS);(CGL);(H2S);(l-OAS);(OASS);,;-ketobutylic;-lyase;;;a;ability;acid;activities;activity;affinity;Ala70;amino;ammonia;analyses;and;antibiotics;are;as;associated;at;bacteria;bacterium;be;been;beta-synthase;binding;both;by;catalyzed;catalyzes;CBS;CBS-;cells;CGL;CGL-encoding;characterized;cluster;crystallographic;cystathionine;decomposed;displays;enzymatic;enzymes;especially;eukaryotic;first;for;form;formation;from;generate;generation;genes;genomes;Glu223;H2S;H2S-generating;has;have;high;hydrogen;important;in;inactivation;including;increases;indicate;interestingly;into;is;it;its;l-cystathionine;l-cysteine;l-cysteine-dependent;l-homocysteine;l-OAS-;l-serine;L.;lactic;Lactobacillus;mainly;major;might;mutational;O-acetyl-l-serine;OASS;occurs;of;pathway;physiological;plant-derived;plantarum;pocket;presence;present;production;properties;recently;recognized;reported;residues;resulting;reverse;second;sequence;shown;shows;similarity;some;study;substrate;sulfhydrylase;sulfide;suppress;suppression;susceptibility;tendency;that;the;their;these;this;those;to;together;toward;transsulfuration;use;various;we;which;whose;with
Hiroshima Univ
Cystathionine beta-synthase (CBS) catalyzes the formation of l-cystathionine from l-serine and l-homocysteine. The resulting l-cystathionine is decomposed into l-cysteine, ammonia, and -ketobutylic acid by cystathionine -lyase (CGL). This reverse transsulfuration pathway, which is catalyzed by both enzymes, mainly occurs in eukaryotic cells. The eukaryotic CBS and CGL have recently been recognized as major physiological enzymes for the generation of hydrogen sulfide (H2S). In some bacteria, including the plant-derived lactic acid bacterium Lactobacillus plantarum, the CBS- and CGL-encoding genes form a cluster in their genomes. Inactivation of these enzymes has been reported to suppress H2S production in bacteria; interestingly, it has been shown that H2S suppression increases their susceptibility to various antibiotics. In the present study, we characterized the enzymatic properties of the L. plantarum CBS, whose amino acid sequence displays a similarity with those of O-acetyl-l-serine sulfhydrylase (OASS) that catalyzes the generation of l-cysteine from O-acetyl-l-serine (l-OAS) and H2S. The L. plantarum CBS shows l-OAS- and l-cysteine-dependent CBS activities together with OASS activity. Especially, it catalyzes the formation of H2S in the presence of l-cysteine and l-homocysteine, together with the formation of l-cystathionine. The high affinity toward l-cysteine as a first substrate and tendency to use l-homocysteine as a second substrate might be associated with its enzymatic ability to generate H2S. Crystallographic and mutational analyses of CBS indicate that the Ala70 and Glu223 residues at the substrate binding pocket are important for the H2S-generating activity.
null
ACTIVE-SITE;ALPHA-AMINOACRYLATE INTERMEDIATE;AMINO-ACIDS;CRYSTAL-STRUCTURE;ESCHERICHIA-COLI;LACTIC-ACID BACTERIA;O-ACETYLSERINE SULFHYDRYLASE;REACTION SPECIFICITY;SALMONELLA-TYPHIMURIUM LT-2;STRUCTURAL BASIS
1
null
amino acid;crystal structure;cystathionine beta-synthase;hydrogen sulfide;Lactobacillus plantarum
21
ESCHERICHIA-COLI;ACTIVE-SITE;ALPHA-AMINOACRYLATE INTERMEDIATE;AMINO-ACIDS;CRYSTAL-STRUCTURE;cystathionine beta-synthase;hydrogen sulfide;LACTIC-ACID BACTERIA;LACTOBACILLUS-PLANTARUM;O-ACETYLSERINE SULFHYDRYLASE;REACTION SPECIFICITY;SALMONELLA-TYPHIMURIUM LT-2;STRUCTURAL BASIS
WOS:000398183800011
Hiroshima Univ, Hiroshima, Japan
Japan
2,017
null
null
null
null
English
null
ACTA CRYSTALLOGR D;ANAL BIOCHEM;APPL ENVIRON MICROB;ARCH BIOCHEM BIOPHYS;BBA-PROTEINS PROTEOM;BIOCHEM CELL BIOL;BIOCHEMISTRY-US;BIOCHIM BIOPHYS ACTA;BIOL CHEM;BIOL PHARM BULL;BIOSCI BIOTECH BIOCH;FEBS LETT;J BACTERIOL;J BIOL CHEM;J INHERIT METAB DIS;J MOL BIOL;METHOD ENZYMOL;NAT REV DRUG DISCOV;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;SCIENCE;STRUCT FOLD DES;YEAST
Izuhara-Kihara, Hisae;Matoba, Yasuyuki;Noda, Masafumi;Sugiyama, Masanori;Yoshida, Tomoki
2024-03-11 ER
Aitken, S M;Bailey, S;Bonner, E R;Brunger, A T;Burkhard, P;Canevari, L;Castro, R;Claus, M T;Cook, P F;Doherty, N C;Ereño-Orbea, J;Holm, L;Hui, T A;Hullo, M F;Jhee, K H;Jin, H K;Kashiwamata, S;Koutmos, M;Kredich, N M;Liu, M;Lodha, P H;Mccorvie, T J;Mcree D.E.;Messerschmidt, A;Miles, E W;Mino, K;Mozzarelli, A;Ono, B I;Otwinowski, Z;Pearson, W R;Rabeh, W M;Schnackerz, K D;Schneider, G;Schnell, R;Shatalin, K;Singh, S;Sun, Q X;Szabó, C;Tai, C H;Thompson, J D;Toney, M D;Willhardt, I;Woehl, E U;Yadav, P K;Zhao, X R;Ågren, D
EQ6IA
Hiroshima, Japan;Hiroshima, Japan.
17
null
1
null
28,127,810
Izuhara-Kihara, Hisae;Matoba, Yasuyuki;Noda, Masafumi;Sugiyama, Masanori;Yoshida, Tomoki
PROTEIN SCI
Hiroshima, Japan
Tan, C M;Villarreal, F
10.1007/s11705-017-1610-x
null
ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES
3h361l1643w533y5d394l4n5d5n650k201i3f
Cell-free systems in the new age of synthetic biology
Univ Calif Davis
null
Tan, CM (corresponding author), Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA.
null
Tan, Cheemeng;Villarreal, Fernando
Engineering, Chemical
Branco-Weiss Fellowship; Human Frontier Science Program
WOS
Tan, C M
Univ Calif Davis, Davis, CA USA
11
age;biology;Cell-Free;in;new;of;synthetic;systems;the
1
Tan, Cheemeng;Villarreal, Fernando
SPRINGER
Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA
Review
Univ Calif Davis
NEW YORK
null
null
Univ Calif Davis
Branco-Weiss Fellowship;Human Frontier Science Program
Tan, CM (corresponding author), Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA.
65
Tan, Cheemeng;Villarreal, Fernando
119
1
398,723,700,007
Branco-Weiss Fellowship;Human Frontier Science Program
USA
FRONTIERS OF CHEMICAL SCIENCE AND ENGINEERING
USA
null
null
Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA
2095-0179
Tan, C M;Villarreal, F
MAR
cmtan@ucdavis.edu
cell-free systems;new age;synthetic biology
2
J
Engineering
advent;application;biomolecules;Cell-free synthetic biology;cell-free system;cell-free systems;cell-free transcription-translation systems;cellular proteins;COMPARTMENTALIZATION;components;composition;COUPLED TRANSCRIPTION;Diagnosis;directed evolution;DIRECTED PEPTIDE-SYNTHESIS;evolution;FREE EXPRESSION SYSTEM;FREE PROTEIN-SYNTHESIS;future direction;GENE-EXPRESSION;historical advancement;IN-VITRO SELECTION;infectious diseases;MESSENGER-RNA;modular control;new age;new applications;rapid design;reconstituted;synthesis;synthetic biology;synthetic genetic circuits;TRANSCRIPTION-TRANSLATION SYSTEM;VACCINES;vision
Villarreal, F
application;cell-free system;COMPARTMENTALIZATION;COUPLED TRANSCRIPTION;DIRECTED PEPTIDE-SYNTHESIS;EVOLUTION;FREE EXPRESSION SYSTEM;FREE PROTEIN-SYNTHESIS;GENE-EXPRESSION;IN-VITRO SELECTION;MESSENGER-RNA;TRANSCRIPTION-TRANSLATION SYSTEM
58
[Villarreal, Fernando; Tan, Cheemeng] Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA.
This work is supported by the Branco-Weiss Fellowship (CT) and the Human Frontier Science Program (CT).
advent;biomolecules;cell-free synthetic biology;cell-free systems;cell-free transcription-translation systems;cellular proteins;components;composition;diagnosis;directed evolution;future direction;historical advancement;infectious diseases;modular control;new applications;rapid design;reconstituted;synthesis;synthetic biology;synthetic genetic circuits;vaccines;vision
10.1002/anie.200701369;10.1002/biot.201400330;10.1002/bit.22385;10.1002/bit.23103;10.1002/bit.24903;10.1002/bit.25587;10.1002/bit.25814;10.1007/978-3-319-27216-0_10;10.1007/S00253-011-3863-5;10.1016/0005-2787(67)90706-X;10.1016/0014-5793(91)81297-L;10.1016/0092-8674(86)90271-0;10.1016/j.bbrc.2012.12.107;10.1016/j.bbrc.2012.12.108;10.1016/j.biotechadv.2014.10.009;10.1016/j.cell.2007.05.045;10.1016/j.cell.2014.10.004;10.1016/j.cell.2016.04.059;10.1016/j.copbio.2010.05.005;10.1016/j.febslet.2014.06.007;10.1016/j.jbiosc.2014.04.019;10.1016/j.jbiotec.2014.02.009;10.1016/j.pep.2005.01.013;10.1016/j.sbi.2015.04.008;10.1016/j.tibtech.2006.06.009;10.1016/j.ymben.2016.03.002;10.1016/j.ymeth.2015.05.020;10.1016/S0378-1119(99)00508-9;10.1021/acssynbio.5b00051;10.1021/acssynbio.5b00296;10.1021/ja301017y;10.1021/jz3019379;10.1021/sb200003v;10.1021/sb200016s;10.1021/sb400131a;10.1038/269532a0;10.1038/35002125;10.1038/90802;10.1038/nbt.1536;10.1038/nbt0798-652;10.1038/ncomms9168;10.1038/NMETH897;10.1038/srep08663;10.1038/srep26257;10.1039/c5lc00700c;10.1073/pnas.0408782102;10.1073/pnas.1201380109;10.1073/pnas.1314585110;10.1073/pnas.57.4.1010;10.1073/pnas.58.4.1669;10.1073/pnas.70.9.2678;10.1073/pnas.71.4.1219;10.1073/pnas.72.5.1922;10.1073/pnas.77.12.7029;10.1073/pnas.94.10.4937;10.1073/pnas.94.23.12297;10.1093/nar/15.8.3257;10.1093/nar/gkt052;10.1093/protein/gzu002;10.1107/S1744309111032143;10.1111/j.1432-1033.1979.tb12791.x;10.1126/science.1255550;10.1126/science.2649980;10.1128/JVI.62.8.2636-2643.1988;10.1128/MCB.9.11.5073;10.1155/2012/371379;10.1162/ARTL_a_00198;10.1182/blood-2006-07-030593;10.1186/1472-6750-8-58;10.1186/1752-0509-6-134;10.1263/jbb.106.8;10.1371/journal.pone.0014388;10.1371/journal.pone.0096635;10.1371/journal.pone.0154614;10.3389/fbioe.2014.00066;10.3389/fchem.2014.00034;10.7554/eLife.09771;[10.1038/NCHEM.1869, 10.1038/nchem.1869];[10.1038/NMETH.1318, 10.1038/nmeth.1318];[10.1038/NNANO.2013.132, 10.1038/nnano.2013.132];[10.1371/journal.pone.0096185, 10.1371/journal.pone.0090225]
Univ Calif Davis
Tan, C M;Villarreal, F
Villarreal, F: Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA
null
null
86
null
USA
Univ Calif Davis
Villarreal, Fernando
null
COMPARTMENTALIZATION;COUPLED TRANSCRIPTION;DIRECTED PEPTIDE-SYNTHESIS;EVOLUTION;FREE EXPRESSION SYSTEM;FREE PROTEIN-SYNTHESIS;GENE-EXPRESSION;IN-VITRO SELECTION;MESSENGER-RNA;TRANSCRIPTION-TRANSLATION SYSTEM
Villarreal, Fernando; Tan, Cheemeng;
null
Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA
Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA
2095-0187
Applications;cell-free systems
1
1967;1973;1974;1975;1977;1979;1980;1983;1986;1987;1988;1989;1991;1997;1998;2000;2001;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016
18
Univ Calif Davis, Dept Biomed Engn, One Shields Ave, Davis, CA 95616 USA
Front. Chem. Sci. Eng.
Tan, Cheemeng
SPRINGER
,;advancement;advent;amenable;and;applications;are;as;biology;biomolecules;cell-free;cellular;circuits;components;composition;control;design;diagnosis;directed;direction;discuss;diseases;evolution;finally;future;genetic;has;here;historical;in;infectious;modular;new;of;on;our;present;proteins;rapid;reconstituted;synthesis;synthetic;systems;the;their;these;to;transcription-translation;ushered;using;vaccines;vision;we;well
Univ Calif Davis
The advent of synthetic biology has ushered in new applications of cell-free transcription-translation systems. These cell-free systems are reconstituted using cellular proteins, and are amenable to modular control of their composition. Here, we discuss the historical advancement of cell-free systems, as well as their new applications in the rapid design of synthetic genetic circuits and components, directed evolution of biomolecules, diagnosis of infectious diseases, and synthesis of vaccines. Finally, we present our vision on the future direction of cell-free synthetic biology.
null
COMPARTMENTALIZATION;COUPLED TRANSCRIPTION;DIRECTED PEPTIDE-SYNTHESIS;EVOLUTION;FREE EXPRESSION SYSTEM;FREE PROTEIN-SYNTHESIS;GENE-EXPRESSION;IN-VITRO SELECTION;MESSENGER-RNA;TRANSCRIPTION-TRANSLATION SYSTEM
5
null
application;cell-free system
8
Applications;cell-free systems;COMPARTMENTALIZATION;COUPLED TRANSCRIPTION;DIRECTED PEPTIDE-SYNTHESIS;EVOLUTION;FREE EXPRESSION SYSTEM;FREE PROTEIN-SYNTHESIS;GENE-EXPRESSION;IN-VITRO SELECTION;MESSENGER-RNA;TRANSCRIPTION-TRANSLATION SYSTEM
WOS:000398723700007
Univ Calif Davis, Davis, CA USA
USA
2,017
null
0000-0002-4034-1243;0000-0003-1049-1192
null
null
English
null
ACS SYNTH BIOL;ACSYNTHETIC BIOL;ACTA CRYSTALLOGR F;ADV EXP MED BIOL;ANGEW CHEM INT EDIT;ARTIF LIFE;BIOCHEM BIOPH RES CO;BIOCHIM BIOPHYS ACTA;BIOTECHNOL ADV;BIOTECHNOL BIOENG;BIOTECHNOL J;BLOOD;BMC BIOTECHNOL;BMC SYST BIOL;CELL;CURR OPIN BIOTECH;CURR OPIN STRUC BIOL;Current Protocols in Molecular Biology;ELIFE;EUR J BIOCHEM;FEBS LETT;Front Bioeng Biotechnol;FRONT CHEM;GENE;J AGRON;J AM CHEM SOC;J BIOSCI BIOENG;J BIOTECHNOL;J NUCLEIC ACIDS;J PHYS CHEM LETT;J SCI FOOD AGR;J VIROL;JOVE-J VIS EXP;LAB CHIP;METAB ENG;METHODS;MOL CELL BIOL;NAT BIOTECHNOL;NAT CHEM;NAT COMMUN;NAT METHODS;NAT NANOTECHNOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;P NATL ACAD SCI-BIOL;PLOS ONE;PROTEIN ENG DES SEL;PROTEIN EXPRES PURIF;SCI REP-UK;SCIENCE;TRENDS BIOTECHNOL
Tan, Cheemeng;Villarreal, Fernando
2024-03-11 ER
Albayrak, C;Bottomley, W;Caschera, F;Chappell, J;Chemla, Y;Chung, B K S;Davies, D H;Deans, T L;Devries, J K;Dodevski, I;Dudley Q, M;Dudley, Q M;Ellis, T;Elowitz, M B;Fujii, S;Fujiwara, K;Gagoski, D;Gallie, D R;Garamella, J;Georgi, V;Gibson, D G;Griffiths, A D;Guild, K;Hanes, J;Hillebrecht, J R;Hong, S H;Hovijitra, N T;Ishihara, G;Jang, S K;Joyce, G F;Kanter, G;Kapsner, K;Karim, A S;Karzbrun, E;Kazuta, Y;Kovtun, O;Kozak, M;Kwon, Y C;Lederman, M;Lewis Daniel, D;Li, J;Lu, Y;Maeda, Y T;Matsuda, T;Miller, O J;Nevin, D E;Niederholtmeyer, H;Niimi, T;Niwa, T;Noren, C J;Oza, J P;Pachuk, C J;Pardee, K;Pelham, H R B;Reichman, M;Roberts, B E;Roberts, R W;Rothblatt, J A;Sachse, R;Schlippe, Y V G;Sharma, B;Shimizu, Y;Shin, J;Singh-Blom, A;Soh, S;Stafford, R L;Stech, M;Steggles, A W;Sumida, T;Sun, Z Z;Tabor S.;Takahashi, M K;Tan, C M;Tawfik, D S;Wang H.;Wang, X;Weitz, M;Yadavalli, R;Yang, H L;Yost, C S;Zawada, J F;Zhang, Y H P;Zhou, H;Zubay, G
ER3UD
Davis, CA USA
23
null
1
null
null
Tan, Cheemeng;Villarreal, Fernando
FRONT CHEM SCI ENG
Davis, CA USA
Bandiera, L;Bevilacqua, A;Cortesi, M;Furini, S;Gherardi, A;Giordano, E;Pasini, A
10.1186/s13036-017-0050-y
8
236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
x204vw1j5g35355w2h493e613q644q6c2k1063
Reliable measurement of <i>E-coli</i> single cell fluorescence distribution using a standard microscope set-up
Univ Bologna
null
Cortesi, M (corresponding author), Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy.
null
Bandiera, Lucia;Bevilacqua, Alessandro;Cortesi, Marilisa;Furini, Simone;Gherardi, Alessandro;Giordano, Emanuele;Pasini, Alice
Biochemical Research Methods;Biotechnology & Applied Microbiology
University of Bologna [RFO 2015]
WOS
Cortesi, M
Univ Bologna, Bologna, Italy;Univ Bologna, Cesena, Italy;Univ Bologna, Ozzano Dell Emilia, Italy;Univ Edinburgh, Midlothian, Scotland;Univ Nottingham, Nottingham, England;Univ Siena, Siena, Italy
11
<i>E-coli</i>;a;cell;distribution;fluorescence;measurement;microscope;of;reliable;set-up;Single;standard;using
2
Bandiera, Lucia;Bevilacqua, Alessandro;Cortesi, Marilisa;Furini, Simone;Gherardi, Alessandro;Giordano, Emanuele;Pasini, Alice
BIOMED CENTRAL LTD
Univ Bologna, Adv Res Ctr Elect Syst Informat & Commun Technol, Bologna, Italy;Univ Bologna, Dept Comp Sci & Engn DISI, Bologna, Italy;Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy;Univ Bologna, Hlth Sci & Technol Interdept Ctr Ind Res HST CIRI, BioEngLab, Ozzano Dell Emilia, Italy;Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland;Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh, Midlothian, Scotland;Univ Nottingham, Sch Med, Div Resp Med, Nottingham, England;Univ Siena, Dept Med Biotechnol, Siena, Italy
Article
Univ Bologna
LONDON
null
null
Univ Bologna;Univ Edinburgh;Univ Nottingham;Univ Siena
University of Bologna
Cortesi, M (corresponding author), Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy.
null
Bandiera, Lucia;Bevilacqua, Alessandro;Cortesi, Marilisa;Furini, Simone;Gherardi, Alessandro;Giordano, Emanuele;Pasini, Alice
11
8
395,925,900,001
University of Bologna [RFO 2015]
Italy;UK
JOURNAL OF BIOLOGICAL ENGINEERING
Italy
null
null
Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy
1754-1611
Bandiera, L;Bevilacqua, A;Cortesi, M;Furini, S;Gherardi, A;Giordano, E;Pasini, A
FEB 20
marilisa.cortesi2@unibo.it
<i>E-coli</i> single cell fluorescence distribution;reliable measurement;standard microscope set-up
7
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
0.99;<i>E-coli</i> single cell fluorescence distribution;acquisition;affordable;affordable measurement/quantification;appropriate software;background;bacterial population;calibration;cellular behaviors;commercial set-ups;complete characterization;comprehension;conclusions;correlation coefficient;custom-made software;data;described;expensive apparatuses;experimental protocol;flow cytometer;Fluorescence microscopy;fluorescent data;fluorescent signal;fundamental;Gene circuits;gene expression;high correlation;image processing-;inter-cellular variability;intercellular variability;laboratories;method;methods;microscope set-up;noise;paper makes quantitative measurement;phenomenon will;Phenotypic noise;presented;protocol;quantitative microscopes);quantitative single-cell fluorescence measurements;reliable measurement;required software;results;same gene circuitry;set-up;significant impact;single cell;single cell fluorescence;single cell fluorescence values;single cell level;single cell level (flow cytometers;Single-cell fluorescence;small laboratories;standard microscope set-up;standard optical microscope;standard optical microscope set-ups;standard optical microscope-;synthetic biology;synthetic biology community (MUSIQ Microscope flUorescence SIngle cell Quantification);synthetic gene circuitry;synthetic gene circuits;system's functionality;tested dynamic range;two experimental set-ups;understanding;validation
Cortesi, M
Fluorescence microscopy;Gene circuits;Phenotypic noise;Single-cell fluorescence;Synthetic biology
null
[Cortesi, Marilisa] Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy. [Bevilacqua, Alessandro; Gherardi, Alessandro; Giordano, Emanuele] Univ Bologna, Adv Res Ctr Elect Syst Informat & Commun Technol, Bologna, Italy. [Bevilacqua, Alessandro] Univ Bologna, Dept Comp Sci & Engn DISI, Bologna, Italy. [Furini, Simone] Univ Siena, Dept Med Biotechnol, Siena, Italy. [Giordano, Emanuele] Univ Bologna, Hlth Sci & Technol Interdept Ctr Ind Res HST CIRI, BioEngLab, Ozzano Dell Emilia, Italy. [Bandiera, Lucia] Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh, Midlothian, Scotland. [Bandiera, Lucia] Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland. [Pasini, Alice] Univ Nottingham, Sch Med, Div Resp Med, Nottingham, England.
University of Bologna RFO 2015 to EG.
0.99;acquisition;affordable;affordable measurement/quantification;appropriate software;background;bacterial population;calibration;cellular behaviors;commercial set-ups;complete characterization;comprehension;conclusions;correlation coefficient;custom-made software;data;described;expensive apparatuses;experimental protocol;flow cytometer;fluorescent data;fluorescent signal;fundamental;gene expression;high correlation;image processing-;inter-cellular variability;intercellular variability;laboratories;method;methods;microscope set-up;noise;paper makes quantitative measurement;phenomenon will;presented;protocol;quantitative microscopes);quantitative single-cell fluorescence measurements;required software;results;same gene circuitry;set-up;significant impact;single cell;single cell fluorescence;single cell fluorescence values;single cell level;single cell level (flow cytometers;small laboratories;standard optical microscope;standard optical microscope set-ups;standard optical microscope-;synthetic biology community (MUSIQ Microscope flUorescence SIngle cell Quantification);synthetic gene circuitry;synthetic gene circuits;system's functionality;tested dynamic range;two experimental set-ups;understanding;validation
10.1007/10_2007_073;10.1007/978-1-61779-567-1_2;10.1016/0378-1119(95)00685-0;10.1016/j.cub.2014.07.036;10.1016/j.jtbi.2016.02.004;10.1021/ac5030232;10.1021/sb200021s;10.1021/sb400089c;10.1038/nprot.2011.432;10.1038/nrmicro2056;10.1088/1742-6596/90/1/012068;10.1098/rspb.1980.0020;10.1172/JCI115251;10.1186/1754-1611-4-14;10.3389/fmicb.2016.00479
Univ Bologna
Bandiera, L;Bevilacqua, A;Cortesi, M;Furini, S;Gherardi, A;Giordano, E;Pasini, A
Cortesi, M: Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy
Bandiera, Lucia;Bevilacqua, Alessandro;Cortesi, Marilisa;Furini, Simone;Gherardi, Alessandro;Giordano, Emanuele
RFO 2015
20
null
Italy
Univ Bologna;Univ Edinburgh;Univ Nottingham;Univ Siena
Cortesi, Marilisa
Green Published, gold
GENE CIRCUITS
Cortesi, Marilisa; Bandiera, Lucia; Pasini, Alice; Bevilacqua, Alessandro; Gherardi, Alessandro; Furini, Simone; Giordano, Emanuele;
null
Univ Bologna, Adv Res Ctr Elect Syst Informat & Commun Technol, Bologna, Italy;Univ Bologna, Dept Comp Sci & Engn DISI, Bologna, Italy;Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy;Univ Bologna, Hlth Sci & Technol Interdept Ctr Ind Res HST CIRI, BioEngLab, Ozzano Dell Emilia, Italy;Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland;Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh, Midlothian, Scotland;Univ Nottingham, Sch Med, Div Resp Med, Nottingham, England;Univ Siena, Dept Med Biotechnol, Siena, Italy
Univ Bologna, Adv Res Ctr Elect Syst Informat & Commun Technol, Bologna, Italy;Univ Bologna, Dept Comp Sci & Engn DISI, Bologna, Italy;Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy;Univ Bologna, Hlth Sci & Technol Interdept Ctr Ind Res HST CIRI, BioEngLab, Ozzano Dell Emilia, Italy;Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland;Univ Edinburgh, SynthSys Ctr Synthet & Syst Biol, Edinburgh, Midlothian, Scotland;Univ Nottingham, Sch Med, Div Resp Med, Nottingham, England;Univ Siena, Dept Med Biotechnol, Siena, Italy
null
Fluorescence microscopy;Phenotypic noise;Single-cell fluorescence;Synthetic biology
null
1980;1991;1996;1998;1999;2007;2008;2009;2010;2011;2012;2013;2014;2016
7
Univ Bologna, Dept Elect, Lab Cellular & Mol Engn S Cavalcanti Elect & Info, Cesena, Italy
J. Biol. Eng.
Giordano, Emanuele
BIOMED CENTRAL LTD
(flow;(MUSIQ;,;0.99;:;>;a;able;accessible;acquire;acquired;acquisition;affordable;all;allow;allows;an;and;apparatuses;appropriate;are;at;available;background;bacterial;be;behaviors;better;between;biology;by;calibration;cell;cellular;characterization;circuitry;circuits;coefficient;commercial;community;compared;complete;comprehension;computed;conclusions;correlation;coupled;custom-made;cytometer;cytometers;data;described;design;due;dynamic;equipped;expensive;experimental;expression;flow;fluorescence;fluorescent;for;freely;from;functionality;fundamental;gene;hardly;high;image;impact;improve;in;inter-cellular;intercellular;is;its;laboratories;level;makes;measurement;measurement/quantification;measurements;method;methods;microscope;microscope-;microscopes);might;noise;obtained;of;on;optical;or;our;over;paper;phenomenon;population;presented;processed;processing-;protocol;proves;Quantification);Quantifying;quantitative;range;required;results;same;set-up;set-ups;signal;significant;single;single-cell;small;software;standard;synthetic;system's;tested;that;the;this;to;together;transformed;two;understanding;used;validation;values;variability;were;when;whose;will;with
Univ Bologna
Background: Quantifying gene expression at single cell level is fundamental for the complete characterization of synthetic gene circuits, due to the significant impact of noise and inter-cellular variability on the system's functionality. Commercial set-ups that allow the acquisition of fluorescent signal at single cell level (flow cytometers or quantitative microscopes) are expensive apparatuses that are hardly affordable by small laboratories. Methods: A protocol that makes a standard optical microscope able to acquire quantitative, single cell, fluorescent data from a bacterial population transformed with synthetic gene circuitry is presented. Single cell fluorescence values, acquired with a microscope set-up and processed with custom-made software, are compared with results that were obtained with a flow cytometer in a bacterial population transformed with the same gene circuitry. Results: The high correlation between data from the two experimental set-ups, with a correlation coefficient computed over the tested dynamic range > 0.99, proves that a standard optical microscope- when coupled with appropriate software for image processing- might be used for quantitative single-cell fluorescence measurements. The calibration of the set-up, together with its validation, is described. Conclusions: The experimental protocol described in this paper makes quantitative measurement of single cell fluorescence accessible to laboratories equipped with standard optical microscope set-ups. Our method allows for an affordable measurement/quantification of intercellular variability, whose better understanding of this phenomenon will improve our comprehension of cellular behaviors and the design of synthetic gene circuits. All the required software is freely available to the synthetic biology community (MUSIQ Microscope flUorescence SIngle cell Quantification).
A-3021-2012;AAE-3932-2021;AAH-6448-2021;AAU-6456-2020;ABE-3400-2021;B-7851-2013
GENE CIRCUITS
0
null
Fluorescence microscopy;Phenotypic noise;Single-cell fluorescence;Synthetic biology
9
Fluorescence microscopy;Gene circuits;Phenotypic noise;Single-cell fluorescence;Synthetic biology
WOS:000395925900001
Univ Bologna, Bologna, Italy;Univ Bologna, Cesena, Italy;Univ Bologna, Ozzano Dell Emilia, Italy;Univ Edinburgh, Midlothian, Scotland;Univ Nottingham, Nottingham, England;Univ Siena, Siena, Italy
Italy;UK
2,017
null
0000-0002-1099-8279;0000-0002-3731-7760;0000-0002-5347-3851;0000-0002-8054-2875;0000-0002-8811-4816;0000-0003-2567-2981;0000-0003-2938-5058
null
null
English
null
ACS SYNTH BIOL;ADV BIOCHEM ENG BIOT;ANAL CHEM;CURR BIOL;FRONT MICROBIOL;GENE;IEEE COMP SOC C;IFMBE PROC;IM PROC THEOR TOOLS;INT J COMPUT CORP RE;J Biol Eng;J CLIN INVEST;J THEOR BIOL;MATLAB TOOLBOX ANAL;METHODS MOL BIOL;NAT PROTOC;NAT REV MICROBIOL;PROC R SOC SER B-BIO
Bandiera, Lucia;Bevilacqua, Alessandro;Cortesi, Marilisa;Furini, Simone;Gherardi, Alessandro;Giordano, Emanuele;Pasini, Alice
2024-03-11 ER
Bandiera, L;Bevilacqua, A;Ceroni Francesca;Ceroni, F;Cohen, S E;Cormack, B P;Giordano, E;Hansen, P C;Ibrahim, S F;Lindstrom Sara;Locke, J C W;Marr, D;Mitsunaga T.;Pothoulakis, G;Selvaggio, G;Singh, P;Vadez, T A;Vicente Nathalie B.;Young Jonathan, W
EN3RP
Cesena, Italy
8
null
4
null
28,239,411
Bandiera, Lucia;Bevilacqua, Alessandro;Cortesi, Marilisa;Furini, Simone;Gherardi, Alessandro;Giordano, Emanuele;Pasini, Alice
J BIOL ENG
Bologna, Italy;Cesena, Italy;Midlothian, Scotland;Nottingham, England;Ozzano Dell Emilia, Italy;Siena, Italy
Chaplain, M A J;Macnamara, C K
10.3934/mbe.2017016
null
PO BOX 2604, SPRINGFIELD, MO 65801-2604 USA
63561k2s5s471sx192534y5v4hs5h363g1t61
SPATIO-TEMPORAL MODELS OF SYNTHETIC GENETIC OSCILLATORS
Univ St Andrews
null
Chaplain, MAJ (corresponding author), Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland.
null
Chaplain, Mark A J;Macnamara, Cicely K
Mathematical & Computational Biology
null
WOS
Chaplain, M A J
Univ St Andrews, Fife, Scotland
14
genetic;MODELS;of;Oscillators;SPATIO-TEMPORAL;synthetic
1
Chaplain, Mark;Macnamara, Cicely Krystyna
AMER INST MATHEMATICAL SCIENCES-AIMS
Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland
Article; Proceedings Paper
Univ St Andrews
SPRINGFIELD
null
International Conference on Micro and Macro Systems in Life Sciences
Univ St Andrews
null
Chaplain, MAJ (corresponding author), Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland.
262
Chaplain, Mark A J;Macnamara, Cicely K
19
1
387,005,500,017
null
UK
MATHEMATICAL BIOSCIENCES AND ENGINEERING
UK
Bedlewo, POLAND
null
Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland
1547-1063
Chaplain, M A J;Macnamara, C K
FEB
ckm@st-andrews.ac.uk;majc@st-andrews.ac.uk
SPATIO-TEMPORAL MODELS;Synthetic Genetic Oscillators
2
J
Mathematical & Computational Biology
(e.g;activator-repressor systems;ACTIVE-TRANSPORT;apoptosis;approach;bifurcation parameter;BINDING;canonical GRN (the Hesl protein);cell division;cellular function;DIFFERENTIATION RESPONSES;DIFFUSION;diffusion coefficient;diffusion-driven oscillations;DYNAMICS;effect;expression;GENE;gene regulatory networks;gene regulatory networks (GRNs);gene sites;gives rise;GRNs;HES1;Hopf bifurcation;i.e;important aspects;major role;MOLECULES;mRNA;n-gene repressilators;NEGATIVE FEEDBACK;negative feedback leading;NETWORK;nucleus;numerical findings;observing fluo-rescently labelled molecules;observing protein/mRNA levels;one important class;OSCILLATIONS;oscillatory behaviour;P53;positive-negative feedback;protein levels;protein production sites;protein/mRNA acts;proteins;proteins bind;recent computational modelling;REPRESSILATORS;signal transduction pathways;single cells);spatial location;spatial movement;SPATIO-TEMPORAL MODELS;synthetic gene networks;synthetic gene regulatory networks;Synthetic Genetic Oscillators;TIME DELAYS;time);transcription factors;transcription rate;vital component
Macnamara, C K
ACTIVE-TRANSPORT;DIFFERENTIATION RESPONSES;DIFFUSION;diffusion-driven oscillations;DYNAMICS;EXPRESSION;gene regulatory networks;HES1;NEGATIVE FEEDBACK;NETWORK;P53;positive-negative feedback;REPRESSILATORS;synthetic gene networks;TIME DELAYS
249
[Macnamara, Cicely K.; Chaplain, Mark A. J.] Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland.
null
(e.g;activator-repressor systems;apoptosis;approach;bifurcation parameter;binding;canonical GRN (the Hesl protein);cell division;cellular function;diffusion coefficient;effect;gene;gene regulatory networks (GRNs);gene sites;gives rise;GRNs;Hopf bifurcation;i.e;important aspects;major role;molecules;mRNA;n-gene repressilators;negative feedback leading;nucleus;numerical findings;observing fluo-rescently labelled molecules;observing protein/mRNA levels;one important class;oscillations;oscillatory behaviour;protein levels;protein production sites;protein/mRNA acts;proteins;proteins bind;recent computational modelling;signal transduction pathways;single cells);spatial location;spatial movement;spatio-temporal models;synthetic gene regulatory networks;time);transcription factors;transcription rate;vital component
10.1007/BF00275860;10.1007/BF00276489;10.1007/s11538-012-9725-1;10.1016/0022-5193(68)90189-6;10.1016/0022-5193(72)90157-9;10.1016/0025-5564(88)90081-8;10.1016/0065-2571(65)90067-1;10.1016/j.bbapap.2013.09.019;10.1016/j.csbj.2014.05.007;10.1016/j.jtbi.2008.07.013;10.1016/j.jtbi.2010.08.017;10.1016/j.jtbi.2010.12.016;10.1016/j.jtbi.2012.08.035;10.1016/j.jtbi.2014.07.022;10.1016/j.mbs.2012.01.001;10.1016/S0014-5793(03)00279-5;10.1016/S0960-9822(03)00494-9;10.1021/sb400152n;10.1038/35002125;10.1038/ncomms5905;10.1038/ng1293;10.1051/mmnp/20094304;10.1063/1.1681157;10.1088/1478-3975/11/4/045001;10.1098/rsif.2010.0183;10.1098/rsif.2012.0988;10.1101/gad.1823109;10.1103/PhysRevE.85.046210;10.1111/j.1365-2443.2010.01413.x;10.1126/science.1074560;10.1126/science.1155998;10.1126/science.1181369;10.1126/science.298.5594.824;10.1137/0911001;10.1140/epjb/e2002-00271-1;10.1142/S021820251550030X;10.1186/gb-2012-13-2-240;10.1242/dev.000786;10.3390/genes2010219;10.3938/jkps.50.234
Univ St Andrews
Chaplain, M A J;Macnamara, C K
Macnamara, C K: Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland
Chaplain, Mark
null
40
null
UK
Univ St Andrews
Macnamara, Cicely K
Green Accepted, gold, Green Submitted
ACTIVE-TRANSPORT;DIFFERENTIATION RESPONSES;DIFFUSION;DYNAMICS;EXPRESSION;HES1;NEGATIVE FEEDBACK;NETWORK;P53;TIME DELAYS
Macnamara, Cicely K.; Chaplain, Mark A. J.;
null
Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland
Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland
1551-0018
diffusion-driven oscillations;gene regulatory networks;positive-negative feedback;repressilator;Synthetic gene network
1
1965;1968;1972;1974;1984;1985;1988;1990;2000;2002;2003;2004;2007;2008;2009;2010;2011;2012;2013;2014;2015
5
Univ St Andrews, Sch Math & Stat, Math Inst, St Andrews KY16 9SS, Fife, Scotland
Math. Biosci. Eng.
Chaplain, Mark A J
AMER INST MATHEMATICAL SCIENCES-AIMS
(e.g;(GRNs);(the;,;a;activator-repressor;acts;altering;and;apoptosis;approach;are;as;aspects;been;behaviour;bifurcation;bind;binding;both;by;canonical;cause;cell;cells);cellular;class;coefficient;component;computational;demonstrated;diffusion;division;e.g.;effect;examine;extend;factors;feedback;findings;first;fluo-rescently;function;gene;gives;GRN;GRNs;has;have;Hesl;Hopf;i.e;if;important;in;is;known;labelled;leading;levels;location;major;many;may;model;modelling;models;molecules;movement;mRNA;n-gene;negative;networks;nucleus;numerical;observing;of;on;one;oscillations;oscillatory;over;paper;parameter;pathways;play;present;production;protein;protein);protein/mRNA;proteins;proved;rate;recent;reduces;regulatory;Repressilators;rigorously;rise;role;show;signal;single;sites;spatial;spatially;spatio-temporal;subsequently;such;synthetic;systems;temporally;that;the;then;there;thereby;these;this;time);to;transcription;transduction;varying;vital;we
Univ St Andrews
Signal transduction pathways play a major role in many important aspects of cellular function e.g. cell division, apoptosis. One important class of signal transduction pathways is gene regulatory networks (GRNs). In many GRNs, proteins bind to gene sites in the nucleus thereby altering the transcription rate. Such proteins are known as transcription factors. If the binding reduces the transcription rate there is a negative feedback leading to oscillatory behaviour in mRNA and protein levels, both spatially (e.g. by observing fluo-rescently labelled molecules in single cells) and temporally (e.g. by observing protein/mRNA levels over time). Recent computational modelling has demonstrated that spatial movement of the molecules is a vital component of GRNs and may cause the oscillations. These numerical findings have subsequently been proved rigorously i.e. the diffusion coefficient of the protein/mRNA acts as a bifurcation parameter and gives rise to a Hopf bifurcation. In this paper we first present a model of the canonical GRN (the Hesl protein) and show the effect of varying the spatial location of gene and protein production sites on the oscillations. We then extend the approach to examine spatio-temporal models of synthetic gene regulatory networks e.g. n-gene repressilators and activator-repressor systems.
A-5355-2010
ACTIVE-TRANSPORT;DIFFERENTIATION RESPONSES;DIFFUSION;DYNAMICS;EXPRESSION;HES1;NEGATIVE FEEDBACK;NETWORKS;P53;TIME DELAYS
0
JUN 08-12, 2015
diffusion-driven oscillations;gene regulatory networks;positive-negative feedback;repressilators;synthetic gene networks
14
ACTIVE-TRANSPORT;DIFFERENTIATION RESPONSES;DIFFUSION;diffusion-driven oscillations;DYNAMICS;EXPRESSION;gene regulatory networks;HES1;NEGATIVE FEEDBACK;NETWORKS;P53;positive-negative feedback;repressilator;synthetic gene networks;TIME DELAYS
WOS:000387005500017
Univ St Andrews, Fife, Scotland
UK
2,017
null
0000-0001-5727-2160;0000-0003-4961-6052
null
null
English
null
ACS SYNTH BIOL;ADVANCE ENZYME REGULAT;B MATH BIOL;BBA-PROTEINS PROTEOM;COMPUT STRUCT BIOTEC;CURR BIOL;DEVELOPMENT;EUR PHYS J B;FEBS LETT;GENE DEV;GENES CELLS;GENES-BASEL;GENOME BIOL;J CHEM PHYS;J KOREAN PHYS SOC;J MATH BIOL;J R SOC INTERFACE;J THEOR BIOL;MATH BIOSCI;MATH MOD METH APPL S;MATH MODEL NAT PHENO;NAT COMMUN;NAT GENET;NATURE;PHYS BIOL;PHYS REV E;SCIENCE;SIAM J SCI STAT COMP
Chaplain, Mark A J;Macnamara, Cicely K
2024-03-11 ER
Busenberg, S;Cangiani, A;Chaplain, M;Chen, Y Y;Dimitrio, L;Elias, J;Elowitz, M B;Glass, L;Goodwin Brian C.;Gordon, K E;Griffith, J S;Hirata, H;Jensen, M H;Kageyama, R;Kobayashi, T;Lahav, G;Lieberman-Aiden, E;Liu, R T;Mahaffy, J M;Milo, R;Momiji, H;Monk, N A M;Naqib, F;O'Brien, E L;Purcell, O;Sang, L Y;Schaerli, Y;Shymko, R M;Skeel, R D;Sturrock, M;Szymanska, Z;Tiana, G;Yordanov, B
EB0AJ
Fife, Scotland
5
null
1
null
27,879,131
Chaplain, Mark A J;Macnamara, Cicely K
MATH BIOSCI ENG
Fife, Scotland
Abdallah, H;Collins, J J;Del Vecchio, D;Qian, Y L
10.1016/j.cels.2016.12.001
null
600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
3i4v5w6a6x5k602i5x5u3p566t2f6x6m2k3l166n
A Blueprint for a Synthetic Genetic Feedback Controller to Reprogram Cell Fate
MIT
null
Del Vecchio, D (corresponding author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;Del Vecchio, D (corresponding author), MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA.
null
Abdallah, Hussein;Collins, James J;Del Vecchio, Domitilla;Qian, Yili
Biochemistry & Molecular Biology;Cell Biology
NIGMS [P50 GMO98792]
WOS
Del Vecchio, D
Broad Inst MIT & Harvard, Cambridge, MA USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Boston, MA USA;MIT, Cambridge, MA USA
4
a;Blueprint;cell;controller;fate;feedback;for;genetic;Reprogram;synthetic;to
1
/0000-0002-1097-0401;Abdallah, Hussein
CELL PRESS
Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA;Harvard Univ, Wyss Inst Biol Inspired Engn, 3 Blackfan Circle, Boston, MA 02115 USA;MIT, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA;MIT, Dept Mech Engn, Cambridge, MA 02139 USA;MIT, Dept Mech Engn, Cambridge, MA 02139 USA.; Del Vecchio, D (corresponding author), MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA;MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA
Article
MIT
CAMBRIDGE
null
null
Broad Inst MIT & Harvard;Dept Mech Engn;Harvard MIT Program Hlth Sci & Technol;Harvard Univ;MIT
NIGMS
Del Vecchio, D (corresponding author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA.; Del Vecchio, D (corresponding author), MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA.
+
Abdallah, Hussein;Collins, James J;Del Vecchio, Domitilla;Qian, Yili
9
8
395,783,200,013
NIGMS [P50 GMO98792]
USA
CELL SYSTEMS
USA;USA.;
null
null
MIT, Dept Mech Engn, Cambridge, MA 02139 USA
2405-4712
Abdallah, H;Collins, J J;Del Vecchio, D;Qian, Y L
JAN 25
ddv@mit.edu
Blueprint;Reprogram Cell Fate;Synthetic Genetic Feedback Controller
4
J
Biochemistry & Molecular Biology;Cell Biology
actual TF concentrations;alternative reprogramming strategy;Blueprint;case study;cell's phenotype;concentration;constant overexpression;controller;controller works;desired value;differentiation;discrepancy;EMBRYONIC STEM-CELLS;experimentalists;expression;feedback gain;gene regulatory networks (GRNs);general;GRN's key TFs;GRN's structure;high;independent;induced pluripotency;inefficient;LINEAGES;MAMMALIAN-CELLS;mathematical analysis;NANOG;new approach;parameters;PLURIPOTENCY;practice;problemby;process;Reprogram Cell Fate;reprogramming;reprogramming GRNs;reprogramming strategy;SELF-RENEWAL;specific transcription factors (TFs);stem cells;Synthetic Genetic Feedback Controller;TF expression;theory;transcription factor;TROPHECTODERM
Del Vecchio, D
DIFFERENTIATION;EMBRYONIC STEM-CELLS;EXPRESSION;LINEAGES;MAMMALIAN-CELLS;NANOG;PLURIPOTENCY;SELF-RENEWAL;transcription factor;TROPHECTODERM
109
[Del Vecchio, Domitilla; Qian, Yili] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Del Vecchio, Domitilla; Collins, James J.] MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA. [Abdallah, Hussein] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Collins, James J.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Collins, James J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Collins, James J.] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA. [Collins, James J.] Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA. [Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, 3 Blackfan Circle, Boston, MA 02115 USA.
The authors would like to thank Prof. Eduardo Sontag and Prof. Ron Weiss for discussions on the monotone cooperative nature of the pluripotency network and on the siRNA technology for the implementation of the feedback controller, respectively. The authors would also like to thank Prof. George Daley for a number of useful discussions both on the reprogrammability property of the pluripotency network and on the feedback controller concept. Finally, the authors would like to thank Ms. Narmada Herath for technical support with the stochastic analysis. This work was supported in part by NIGMS grant P50 GMO98792.
actual TF concentrations;alternative reprogramming strategy;case study;cell's phenotype;concentration;constant overexpression;controller;controller works;desired value;discrepancy;experimentalists;feedback gain;gene regulatory networks (GRNs);general;GRN's key TFs;GRN's structure;high;independent;induced pluripotency;inefficient;mathematical analysis;new approach;parameters;practice;problemby;process;reprogram cell fate;reprogramming;reprogramming GRNs;reprogramming strategy;specific transcription factors (TFs);stem cells;synthetic genetic feedback controller;TF expression;theory
10.1002/bies.200800189;10.1006/dbio.1994.1312;10.1016/j.cell.2005.08.020;10.1016/j.cell.2005.08.040;10.1016/j.cell.2006.07.024;10.1016/j.cell.2008.01.015;10.1016/j.cell.2008.02.039;10.1016/j.cell.2009.01.035;10.1016/j.cell.2009.12.029;10.1016/j.cell.2010.10.008;10.1016/j.cell.2011.05.017;10.1016/j.cell.2012.09.045;10.1016/j.cell.2013.05.001;10.1016/j.stem.2011.11.003;10.1016/j.stem.2014.05.002;10.1016/j.stem.2015.01.013;10.1016/S0092-8674(03)00392-1;10.1017/CBO9780511809088;10.1021/acssynbio.6b00014;10.1038/74199;10.1038/cr.2013.1;10.1038/msb.2013.49;10.1038/mt.2010.314;10.1038/nature08533;10.1038/nature08592;10.1038/nature10098;10.1038/nbt.2018;10.1038/nbt.3070;10.1038/ncb2742;10.1038/NMETH1079;10.1038/nrg3853;10.1038/nrm.2016.8;10.1038/nrm3584;10.1038/nsmb1280;10.1038/nsmb780;10.1038/srep00550;10.1038/srep13533;10.1042/BJ20080134;10.1063/1.481811;10.1073/pnas.0802288105;10.1073/pnas.1017017108;10.1093/dnares/dsn030;10.1093/nar/gkp889;10.1101/gad.1833510;10.1109/TAC.2003.817920;10.1109/TAC.2012.2211444;10.1128/JVI.65.1.483-488.1991;10.1186/1752-0509-5-19;10.1371/journal.pbio.1000149;10.1371/journal.pcbi.0020123;10.1371/journal.pcbi.1003165;10.1371/journal.pcbi.1003625;10.1371/journal.pcbi.1004881;10.1371/journal.pone.0003478;10.1371/journal.pone.0081622;10.1371/journal.pone.0092496;10.1371/journal.pone.0102873;10.23943/PRINCETON/9780691161532.001.0001;[10.1016/j.cels.2016.01.004, 10.1016/j.cels.2016.02.010]
MIT
Abdallah, H;Collins, J J;Del Vecchio, D;Qian, Y L
Del Vecchio, D: MIT, Dept Mech Engn, Cambridge, MA 02139 USA
Qian, Yili
P50 GMO98792
69
null
USA
Broad Inst MIT & Harvard;Harvard MIT Program Hlth Sci & Technol;Harvard Univ;MIT
Del Vecchio, Domitilla
Green Accepted, hybrid
DIFFERENTIATION;EMBRYONIC STEM-CELLS;EXPRESSION;LINEAGES;MAMMALIAN-CELLS;NANOG;PLURIPOTENCY;SELF-RENEWAL;TRANSCRIPTION FACTOR;TROPHECTODERM
Del Vecchio, Domitilla; Abdallah, Hussein; Qian, Yili; Collins, James J.;
null
Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA;Harvard Univ, Wyss Inst Biol Inspired Engn, 3 Blackfan Circle, Boston, MA 02115 USA;MIT, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA;MIT, Dept Mech Engn, Cambridge, MA 02139 USA;MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA
Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA;Harvard Univ, Wyss Inst Biol Inspired Engn, 3 Blackfan Circle, Boston, MA 02115 USA;MIT, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA;MIT, Dept Mech Engn, Cambridge, MA 02139 USA;MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA
2405-4720
null
1
1964;1991;1994;1995;2000;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016
51
MIT, Dept Mech Engn, Cambridge, MA 02139 USA;MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA
Cell Syst.
Collins, James J
CELL PRESS
(GRNs);(TFs);,;:;a;actual;address;adjusting;alternative;an;analysis;and;any;apply;approach;artificially;as;based;be;between;by;can;case;cell;cell's;cells;concentration;concentrations;constant;controller;demonstrate;desired;discrepancy;dynamically;experimentalists;expression;factors;fate;feedback;gain;gene;general;genetic;GRN's;GRNs;guaranteed;here;high;in;independent;induced;inefficient;instead;introducing;is;its;key;maintain;manipulate;mathematical;may;model;networks;new;not;of;often;on;overexpression;parameters;performance;performed;phenotype;pluripotency;practice;predicts;problemby;process;propose;provided;regulatory;reprogram;reprogramming;specific;steers;stem;strategy;structure;study;succeed;sufficiently;synthetic;TF;TFs;that;the;theory;this;to;transcription;unreliable;using;value;we;works
MIT
To artificially reprogram cell fate, experimentalists manipulate the gene regulatory networks (GRNs) that maintain a cell's phenotype. In practice, reprogramming is often performed by constant overexpression of specific transcription factors (TFs). This process can be unreliable and inefficient. Here, we address this problemby introducing a new approach to reprogramming based on mathematical analysis. We demonstrate that reprogramming GRNs using constant overexpression may not succeed in general. Instead, we propose an alternative reprogramming strategy: a synthetic genetic feedback controller that dynamically steers the concentration of a GRN's key TFs to any desired value. The controller works by adjusting TF expression based on the discrepancy between desired and actual TF concentrations. Theory predicts that this reprogramming strategy is guaranteed to succeed, and its performance is independent of the GRN's structure and parameters, provided that feedback gain is sufficiently high. As a case study, we apply the controller to a model of induced pluripotency in stem cells.
L-5558-2019
DIFFERENTIATION;EMBRYONIC STEM-CELLS;EXPRESSION;LINEAGE;MAMMALIAN-CELLS;NANOG;PLURIPOTENCY;SELF-RENEWAL;TRANSCRIPTION FACTORS;TROPHECTODERM
1
null
null
23
DIFFERENTIATION;EMBRYONIC STEM-CELLS;EXPRESSION;LINEAGE;MAMMALIAN-CELLS;NANOG;PLURIPOTENCY;SELF-RENEWAL;transcription factor;TROPHECTODERM
WOS:000395783200013
Broad Inst MIT & Harvard, Cambridge, MA USA;Harvard MIT Program Hlth Sci & Technol, Cambridge, MA USA;Harvard Univ, Boston, MA USA;MIT, Cambridge, MA USA
USA
2,017
null
0000-0002-1097-0401;0000-0003-3860-3598
null
null
English
null
ACS SYNTH BIOL;AM MATH SOC MATH SUR;BIOCHEM J;BIOESSAYS;BMC SYST BIOL;CELL;CELL RES;CELL STEM CELL;CELL SYST;DEV BIOL;DIFFERENTIAL INTEGRA;DNA RES;GENE DEV;IEEE T AUTOMAT CONTR;INTRO SYSTEMS BIOL D;Introduction to Lattices and Order;J CHEM PHYS;J VIROL;MOL SYST BIOL;MOL THER;NAT BIOTECHNOL;NAT CELL BIOL;NAT GENET;NAT METHODS;NAT REV GENET;NAT REV MOL CELL BIO;NAT STRUCT MOL BIOL;NATURE;Nonlinear Systems;NUCLEIC ACIDS RES;NUMERICAL OPTIMIZATI;Numerical Solution of Stochastic Differential Equations;P NATL ACAD SCI USA;PLOS BIOL;PLOS COMPUT BIOL;PLOS ONE;Real-time optimization by extremum-seeking control;SCI REP-UK;The Strategy of the Genes
Abdallah, Hussein;Collins, James J;Del Vecchio, Domitilla;Qian, Yili
2024-03-11 ER
Alon, U;Angeli, D;Ariyur Kb.;Boyer, L A;Briat, C;Cahan, P;Carey, B W;Carthew, R W;Chambers, I;Chickarmane, V;Cuccato, G;Darzacq, X;Davey B.A.;Del Vecchio D.;Del Vecchio, D;Descalzo, S M;Ebert, M S;Faucon, P C;Feng, H D;Gillespie, D T;Goh, P A;Graf, T;Haley, B;Hanna, J;Hanna, J H;Herberg, M;Holtz, W J;Huang, S;Jaenisch, R;Jens, M;Kalmar, T;Khalil H. K.;Kim, J W;Kloeden P.;Li, C H;Menolascina, F;Milias-Argeitis, A;Milo, R;Morris, S A;Mullin, N P;Murray Richardm.;Niakan, K K;Nikolaev, E V;Niwa, H;Nocedal J.;Palmieri, S L;Radzisheuskaya, A;Schlaeger, T M;Schwanhäusser, B;Sharova, L V;Shu, J;Siwiak M.;Smith H.L.;Soufi, A;Takahashi, K;Tapia, N;Theunissen, T W;Thomson, M;Waddington C.;Walter, W;Wang, J;Warlich, E;Xu, J;Yates, J L
EN1PV
Cambridge, MA USA;Cambridge, MA USA.
62
null
4
null
28,065,574
Abdallah, Hussein;Collins, James J;Del Vecchio, Domitilla;Qian, Yili
CELL SYST
Boston, MA USA;Cambridge, MA USA
Blanchard, A E;Kong, W T;Liao, C;Lu, T
10.1093/nar/gkw1045
null
GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
6kmz6v4i2z6b626de5a5u401g3q176y32y26
Engineering robust and tunable spatial structures with synthetic gene circuits
Univ Illinois
null
Lu, T (corresponding author), Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA.;Lu, T (corresponding author), Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.;Lu, T (corresponding author), Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
null
Blanchard, Andrew E;Kong, Wentao;Liao, Chen;Lu, Ting
Biochemistry & Molecular Biology
National Science Foundation [1227034, 1553649]; Office of Naval Research [N000141612525]; American Heart Association [12SDG12090025]; Brain and Behavior Research Foundation (NARSAD Young Investigator Award); U.S. Department of Defense (DOD) [N000141612525] Funding Source: U.S. Department of Defense (DOD); Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1553649] Funding Source: National Science Foundation; Directorate For Engineering; Div Of Engineering Education and Centers [1227034] Funding Source: National Science Foundation
WOS
Lu, T
Univ Illinois, Urbana, IL USA
45
and;circuits;engineering;gene;robust;spatial;structures;synthetic;tunable;with
1
Liao, Chen
OXFORD UNIV PRESS
Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Dept Phys, Urbana, IL 61801 USA;Univ Illinois, Dept Phys, Urbana, IL 61801 USA
Article
Univ Illinois
OXFORD
null
null
Univ Illinois
American Heart Association;Brain and Behavior Research Foundation (NARSAD Young Investigator Award);Direct For Biological Sciences;Directorate For Engineering;Div Of Engineering Education and Centers;Div Of Molecular and Cellular Bioscience;National Science Foundation;Office of Naval Research;U.S. Department of Defense (DOD)
Lu, T (corresponding author), Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA.; Lu, T (corresponding author), Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
1014
Blanchard, Andrew E;Kong, Wentao;Liao, Chen;Lu, Ting
23
3
396,576,300,045
American Heart Association [12SDG12090025];Brain and Behavior Research Foundation (NARSAD Young Investigator Award);Direct For Biological Sciences;Directorate For Engineering;Div Of Engineering Education and Centers [1227034] Funding Source: National Science Foundation;Div Of Molecular and Cellular Bioscience [1553649] Funding Source: National Science Foundation;National Science Foundation [1227034, 1553649];Office of Naval Research [N000141612525];U.S. Department of Defense (DOD) [N000141612525] Funding Source: U.S. Department of Defense (DOD)
USA
NUCLEIC ACIDS RESEARCH
USA;USA.;
null
null
Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA
0305-1048
Blanchard, A E;Kong, W T;Liao, C;Lu, T
JAN
luting@illinois.edu
engineering;synthetic gene circuits;tunable spatial structures
4
J
Biochemistry & Molecular Biology
antibiotic features;band widths;biological systems;BIOLOGY;biosynthesis;cells;cellular context perturbations;cellular nisin immunity;cellular stripes;circuit robustness;CIRCUITS;controllable;controllable arrays;deep mining;DESIGN;designed patterns;direct cells;direct Lactococcus lactis populations;dual signaling;engineering;external nisin gradient;foundations;functional robustness;future applications;goal;GRADIENT;living systems;major goal;mathematical model;multiple species;natural functionalities;nisin;observed patterns;patterns;predictable structures;promising tools;simple synthetic circuits;SPACE;spatial band-pass;spatial structures;spots;structured nisin-producing bacteria;study offers new synthetic biology tools;synthetic communities;synthetic gene circuits;tunability;tunable;tunable spatial structures;valuable route
Kong, W T
BIOLOGY;BIOSYNTHESIS;DESIGN;FOUNDATIONS;SPACE
1005
[Kong, Wentao; Liao, Chen; Lu, Ting] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Kong, Wentao; Blanchard, Andrew E.; Liao, Chen; Lu, Ting] Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA. [Blanchard, Andrew E.; Lu, Ting] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
National Science Foundation [1227034, 1553649]; Office of Naval Research [N000141612525]; American Heart Association [12SDG12090025]; Brain and Behavior Research Foundation (NARSAD Young Investigator Award). Funding for open access charge: National Science Foundation.
antibiotic features;band widths;biological systems;cells;cellular context perturbations;cellular nisin immunity;cellular stripes;circuit robustness;circuits;controllable;controllable arrays;deep mining;designed patterns;direct cells;direct Lactococcus lactis populations;dual signaling;engineering;external nisin gradient;functional robustness;future applications;goal;gradient;living systems;major goal;mathematical model;multiple species;natural functionalities;nisin;observed patterns;patterns;predictable structures;promising tools;simple synthetic circuits;space;spatial band-pass;spatial structures;spots;structured nisin-producing bacteria;study offers new synthetic biology tools;synthetic communities;synthetic gene circuits;tunability;tunable;valuable route
10.1007/s00018-007-7171-2;10.1016/j.cell.2009.04.048;10.1016/j.cell.2016.03.006;10.1016/j.tibtech.2008.05.004;10.1021/sb300044r;10.1021/sb500225r;10.1038/463288a;10.1038/msb.2008.24;10.1038/msb4100202;10.1038/nature03461;10.1038/nature04342;10.1038/nature08753;10.1038/nbt.1591;10.1038/nbt0708-771;10.1038/ncomms5905;10.1038/nrg1471;10.1038/nrg3227;10.1073/pnas.0901246106;10.1093/nar/gkq671;10.1093/nar/gkv1093;10.1103/RevModPhys.66.1481;10.1126/science.1206843;10.1126/science.1209042;10.1126/science.8493529;10.1126/science.aaa3794;10.1128/AEM.55.1.224-228.1989;10.1128/AEM.58.6.1952-1961.1992;10.1128/JB.180.7.1895-1903.1998;10.1146/annurev.micro.52.1.779;[10.1038/NMETH.2926, 10.1038/nmeth.2926]
Univ Illinois
Blanchard, A E;Kong, W T;Liao, C;Lu, T
Kong, W T: Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA
null
1227034;12SDG12090025;1553649;N000141612525
34
null
USA
Univ Illinois
Kong, Wentao
Green Published, gold, Green Submitted
BIOLOGY;BIOSYNTHESIS;DESIGN;FOUNDATIONS;SPACE
Kong, Wentao; Blanchard, Andrew E.; Liao, Chen; Lu, Ting;
null
Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA;Univ Illinois, Dept Phys, Urbana, IL 61801 USA
Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA;Univ Illinois, Dept Phys, Urbana, IL 61801 USA
1362-4962
null
2
1989;1992;1993;1994;1998;2001;2004;2005;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016
35
Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA;Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA;Univ Illinois, Dept Phys, Urbana, IL 61801 USA
Nucleic Acids Res.
Lu, Ting
OXFORD UNIV PRESS
,;;;a;achieve;additionally;against;all;allow;also;although;and;antibiotic;applications;are;arrays;bacteria;band;band-pass;become;biological;biology;both;build;by;can;cells;cellular;circuit;circuits;communities;composed;consistently;context;controllable;deep;demonstrates;designed;direct;do;driven;dual;engineering;environmental;establish;even;external;facilitate;features;fine-tuning;for;form;functional;functionalities;furthermore;future;gene;generate;goal;gradient;harnessing;have;here;highly;however;immunity;in;is;it;lactis;Lactococcus;living;major;mathematical;mining;model;multiple;natural;need;new;nisin;nisin-producing;not;observed;of;offers;order;patterning;patterns;perturbations;populations;possess;predictable;program;programmed;promising;recently;reproduces;require;robust;robustness;route;show;signaling;simple;space;spatial;species;specified;spots;stripes;structured;structures;study;successfully;synthetic;systems;that;the;their;they;this;to;tools;tunability;tunable;us;valuable;we;when;widths;with
Univ Illinois
Controllable spatial patterning is a major goal for the engineering of biological systems. Recently, synthetic gene circuits have become promising tools to achieve the goal; however, they need to possess both functional robustness and tunability in order to facilitate future applications. Here we show that, by harnessing the dual signaling and antibiotic features of nisin, simple synthetic circuits can direct Lactococcus lactis populations to form programmed spatial band-pass structures that do not require fine-tuning and are robust against environmental and cellular context perturbations. Although robust, the patterns are highly tunable, with their band widths specified by the external nisin gradient and cellular nisin immunity. Additionally, the circuits can direct cells to consistently generate designed patterns, even when the gradient is driven by structured nisin-producing bacteria and the patterning cells are composed of multiple species. A mathematical model successfully reproduces all of the observed patterns. Furthermore, the circuits allow us to establish predictable structures of synthetic communities and controllable arrays of cellular stripes and spots in space. This study offers new synthetic biology tools to program spatial structures. It also demonstrates that a deep mining of natural functionalities of living systems is a valuable route to build circuit robustness and tunability.
null
BIOLOGY;BIOSYNTHESIS;DESIGN;FOUNDATIONS;SPACE
2
null
null
10
BIOLOGY;BIOSYNTHESIS;DESIGN;FOUNDATIONS;SPACE
WOS:000396576300045
Univ Illinois, Urbana, IL USA
USA
2,017
null
0000-0001-8474-1196
null
null
English
null
ABSTR APPL AN;ACS SYNTH BIOL;ANNU REV MICROBIOL;APPL ENVIRON MICROB;BIORESOUR BIOPROCESS;CELL;CELL MOL LIFE SCI;EMBRYONIC DEV DROSOP;J BACTERIOL;MATH BIOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT COMMUN;NAT METHODS;NAT REV GENET;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;REV MOD PHYS;SCIENCE;TRENDS BIOTECHNOL
Blanchard, Andrew E;Kong, Wentao;Liao, Chen;Lu, Ting
2024-03-11 ER
[Anonymous];Arkin, A;Balagadde, F K;Basu, S;Ben-Jacob, E;Brenner, K;Brophy, J A N;Campos-Ortega J. A.;Cao, Y X L;Chen, Y;Danino, T;Endy, D;Greber, D;Kitano, H;Koch, A J;Kong, W;Kong, W T;Kwok, R;Langer, R;Le Loir, Y;Liu, C L;Lu, T K;Lubelski, J;Murray J.D;Riccione, K A;Ruder, W C;Schaerli, Y;Serrano, L;Slusarczyk, A L;Sohka, T;Stoddard, G W;Tabor, J J;Vandeguchte, M
EO3DY
Urbana, IL USA;Urbana, IL USA.
44
null
1
null
27,899,571
Blanchard, Andrew E;Kong, Wentao;Liao, Chen;Lu, Ting
NUCLEIC ACIDS RES
Urbana, IL USA
MacPherson, M;Saka, Y
10.1021/acssynbio.6b00165
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
74b5q696i316h54f1s1h4l3o3d6np71285c
Short Synthetic Terminators for Assembly of Transcription Units <i>in Vitro</i> and Stable Chromosomal Integration in Yeast <i>S</i>. <i>cerevisiae</i>
Univ Aberdeen
null
Saka, Y (corresponding author), Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
null
MacPherson, Murray;Saka, Yasushi
Biochemical Research Methods
Scottish Universities Life Sciences Alliance (SULSA)
WOS
Saka, Y
Univ Aberdeen, Aberdeen AB25 2ZD, Scotland
6
<i>in;<i>S</i>;and;Assembly;Chromosomal;for;i>cerevisiae</i>;in;integration;of;short;Stable;synthetic;Terminators;transcription;Units;Vitro</i>;yeast
1
null
AMER CHEMICAL SOC
Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
Article
Univ Aberdeen
WASHINGTON
null
null
Univ Aberdeen
Scottish Universities Life Sciences Alliance (SULSA)
Saka, Y (corresponding author), Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
138
MacPherson, Murray;Saka, Yasushi
36
1
392,575,700,015
Scottish Universities Life Sciences Alliance (SULSA)
UK
ACS SYNTHETIC BIOLOGY
UK
null
null
Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
2161-5063
MacPherson, M;Saka, Y
JAN
y.saka@abdn.ac.uk
Assembly;i>cerevisiae</i>;short Synthetic Terminators;Stable Chromosomal Integration;Transcription Units <i>in Vitro</i>;Yeast <i>S</i>
2
J
Biochemistry & Molecular Biology
assembled DNA;assembling multiple transcription units;assembly;bacterial artificial chromosome;BINDING PROTEINS NRD1;central;common consensus;consensus sequence;CONSTRUCTION;CRYPTIC UNSTABLE TRANSCRIPTS;DESIGN;different activities;DNA;efficient assembly;efficient homologous recombination;expression vectors;few homologous segments;Gateway recombination reactions;gene assembly;GENE-EXPRESSION;genome;genomic integration;i>cerevisiae</i>;ideal chassis;identical length;impacts;influence;integration;issue;lead;library;method;multigene assemblies;neighboring transcription units;orthogonal genetic components;PATHWAY;problem;property;proximal transcription units;random linkers;rearrangements;RECOMBINATION;repeated usage;repeats;repetitive sequences;Saccharomyces cerevisiae;SACCHAROMYCES-CEREVISIAE;short Synthetic Terminators;stable;Stable Chromosomal Integration;standard parts;synthetic;synthetic biology;synthetic genes;synthetic genetic circuits;synthetic genome assemblies;synthetic terminators;SYSTEM;tandem array;transcription units;Transcription Units <i>in Vitro</i>;transcriptional terminator;transcriptional terminators;two BAC (bacterial artificial chromosome) vectors;vitro;vivo;yeast;Yeast <i>S</i>;yeast genome;yeast S. cerevisiae
MacPherson, M
bacterial artificial chromosome;BINDING PROTEINS NRD1;CONSTRUCTION;CRYPTIC UNSTABLE TRANSCRIPTS;DESIGN;DNA;gene assembly;GENE-EXPRESSION;PATHWAY;RECOMBINATION;Saccharomyces cerevisiae;SACCHAROMYCES-CEREVISIAE;SYSTEM;transcriptional terminator;YEAST
130
[MacPherson, Murray; Saka, Yasushi] Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
The authors acknowledge the assistance of the lain Fraser Cytometry Centre at the University of Aberdeen. We also thank Claire MacGregor, Diane Massie, and Yvonne Turnbull for technical assistance, Alexander Lorenz and Ryohei Sekido for critical reading of the manuscript, and Richard Newton for preliminary results. This work was supported by the Scottish Universities Life Sciences Alliance (SULSA).
assembled DNA;assembling multiple transcription units;assembly;central;common consensus;consensus sequence;different activities;efficient assembly;efficient homologous recombination;expression vectors;few homologous segments;Gateway recombination reactions;genome;genomic integration;ideal chassis;identical length;impacts;influence;integration;issue;lead;library;method;multigene assemblies;neighboring transcription units;orthogonal genetic components;problem;property;proximal transcription units;random linkers;rearrangements;repeated usage;repeats;repetitive sequences;short synthetic terminators;stable;standard parts;synthetic;synthetic biology;synthetic genes;synthetic genetic circuits;synthetic genome assemblies;synthetic terminators;system;tandem array;transcription units;transcriptional terminators;two BAC (bacterial artificial chromosome) vectors;vitro;vivo;yeast;yeast genome;yeast S. cerevisiae
10.1002/1097-0061(200010)16:14<1313::AID-YEA626>3.0.CO;2-O;10.1002/yea.1469;10.1016/0378-1119(87)90376-3;10.1016/j.cell.2005.04.030;10.1016/j.cell.2013.10.024;10.1016/j.molcel.2006.07.024;10.1016/j.molcel.2006.07.029;10.1016/j.ymben.2013.07.001;10.1016/S0968-0004(96)10057-8;10.1021/acssynbio.5b00007;10.1021/acssynbio.5b00174;10.1021/sb300116y;10.1021/sb4001323;10.1021/sb500255k;10.1021/sb5003357;10.1021/sb500356d;10.1021/sb500366v;10.1021/sb500372z;10.1038/nature09652;10.1038/ncomms5002;10.1038/nprot.2014.145;10.1073/pnas.0507783103;10.1073/pnas.1100507108;10.1073/pnas.76.10.4951;10.1074/jbc.M109.007948;10.1093/nar/23.15.3079;10.1093/nar/gkt1101;10.1093/nar/gkt135;10.1093/nar/gkt605;10.1093/nar/gkt860;10.1093/nar/gkt915;10.1093/nar/gku1082;10.1093/nar/gku829;10.1093/nar/gkv466;10.1101/gr.182477.114;10.1111/1567-1364.12188;10.1126/science.1151721;10.1126/science.1224350;10.1126/science.1249252;10.1186/1471-2105-11-346;10.1261/rna.338407;10.1371/journal.pone.0016765;10.1371/journal.pone.0021622;10.1371/journal.pone.0064419;10.7554/eLife.03703;[10.1038/NMETH.1318, 10.1038/nmeth.1318];[10.1038/NMETH.3339, 10.1038/nmeth.3339]
Univ Aberdeen
MacPherson, M;Saka, Y
MacPherson, M: Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
null
null
51
null
UK
Univ Aberdeen
MacPherson, Murray
Green Accepted
BINDING PROTEINS NRD1;CONSTRUCTION;CRYPTIC UNSTABLE TRANSCRIPTS;DESIGN;DNA;GENE-EXPRESSION;PATHWAY;RECOMBINATION;SACCHAROMYCES-CEREVISIAE;SYSTEM
MacPherson, Murray; Saka, Yasushi;
null
Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
null
Saccharomyces cerevisiae;yeast;bacterial artificial chromosome;gene assembly;transcription termination
1
1979;1987;1989;1995;1996;2000;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016
17
Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
ACS Synth. Biol.
Saka, Yasushi
AMER CHEMICAL SOC
(bacterial;,;a;activities;address;all;also;although;an;and;are;array;artificial;as;assembled;assemblies;assembling;assembly;avoid;BAC;based;be;because;biology;by;can;central;cerevisiae;chassis;chromosome);circuits;common;components;consensus;constructed;constructs;designed;developing;different;DNA;efficient;exploiting;expression;few;for;Gateway;genes;genetic;genome;genomic;has;have;highly;homologous;however;ideal;identical;impacts;in;influence;integrated;integration;is;issue;its;lead;length;library;linkers;method;multigene;multiple;neighboring;of;on;Orthogonal;particular;parts;poses;problem;property;proven;proximal;random;reactions;rearrangements;recombination;repeated;repeats;repetitive;S.;segments;sequence;sequences;series;set;short;showed;since;stable;standard;such;synthetic;system;tandem;terminators;tested;the;their;there;these;they;this;to;transcription;transcriptional;two;units;usage;using;vectors;vitro;vivo;we;with;yeast
Univ Aberdeen
Assembly of synthetic genetic circuits is central to synthetic biology. Yeast S. cerevisiae, in particular, has proven to be an ideal chassis for synthetic genome assemblies by exploiting its efficient homologous recombination. However, this property of efficient homologous recombination poses a problem for multigene assemblies in yeast, since repeated usage of standard parts, such as transcriptional terminators, can lead to rearrangements of the repeats in assembled DNA constructs in vivo. To address this issue in developing a library of orthogonal genetic components for yeast, we designed a set of short synthetic terminators based on a consensus sequence with random linkers to avoid repetitive sequences. We constructed a series of expression vectors with these synthetic terminators for efficient assembly of synthetic genes using Gateway recombination reactions. We also constructed two BAC (bacterial artificial chromosome) vectors for assembling multiple transcription units with the synthetic terminators in vitro and their integration in the yeast genome. The tandem array of synthetic genes integrated in the genome by this method is highly stable because there are few homologous segments in the synthetic constructs. Using this system of assembly and genomic integration of transcription units, we tested the synthetic terminators and their influence on the proximal transcription units. Although all the synthetic terminators have the common consensus with the identical length, they showed different activities and impacts on the neighboring transcription units.
null
BINDING PROTEINS NRD1;CONSTRUCTION;CRYPTIC UNSTABLE TRANSCRIPTS;DESIGN;DNA;GENE-EXPRESSION;PATHWAY;RECOMBINATION;SACCHAROMYCES-CEREVISIAE;SYSTEM
2
null
bacterial artificial chromosome;gene assembly;Saccharomyces cerevisiae;transcriptional terminator;yeast
9
SACCHAROMYCES-CEREVISIAE;YEAST;bacterial artificial chromosome;BINDING PROTEINS NRD1;CONSTRUCTION;CRYPTIC UNSTABLE TRANSCRIPTS;DESIGN;DNA;gene assembly;GENE-EXPRESSION;PATHWAY;RECOMBINATION;SYSTEM;transcription termination
WOS:000392575700015
Univ Aberdeen, Aberdeen AB25 2ZD, Scotland
UK
2,017
null
null
null
null
English
null
ACS SYNTH BIOL;BMC BIOINFORMATICS;CELL;ELIFE;FEMS YEAST RES;GENE;GENETICS;GENOME RES;J BIOL CHEM;METAB ENG;MOL CELL;MOL CELL BIOL;NAT COMMUN;NAT METHODS;NAT PROTOC;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;RNA;SCIENCE;TRENDS BIOCHEM SCI;YEAST
MacPherson, Murray;Saka, Yasushi
2024-03-11 ER
Agmon, N;Amberg Dc.;Annaluru, N;Arigo, J T;Bao, Z H;Carroll, K L;Casini, A;Ceroni, F;Churchman, L S;Colloms, S D;Curran, K A;Davis, C A;Dicarlo, J E;Duportet, X;El Kaderi, B;Gibson, D G;Giuraniuc, C V;Guo, Z J;Guye, P;Jakociunas, T;Langlerouault, F;Lee, M E;Li, M;Lin, M T;Ma, H;Mateus, C;Mitchell, L A;Redden, H;Ryan, O W;Sadowski, I;Sarrion-Perdigones, A;Scherer, S;Schulz, D;Sikorski, R S;Storch, M;Suzuki, Y;Tan-Wong, S M;Thiebaut, M;Torella, J P;Trubitsyna, M;Weber, E;Wingler, L M;Wyers, F;Xi, L Q;Yamanishi, M
EI5ZV
Aberdeen AB25 2ZD, Scotland
23
null
1
null
27,529,501
MacPherson, Murray;Saka, Yasushi
ACS SYNTH BIOL
Aberdeen AB25 2ZD, Scotland
Re, A
10.3389/fcell.2017.00077
77
AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND
5t2l23661j64182g53305gf624d6d261u6r6673
nSynthetic Gene Expression Circuits for Designing Precision Tools in Oncology
Ist Italiano Tecnol
null
Re, A (corresponding author), Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy.
null
Re, Angela
Cell Biology;Developmental Biology
Istituto Italiano di Tecnologia
WOS
Re, A
Ist Italiano Tecnol, Turin, Italy
5
circuits;Designing;expression;for;gene;in;nSynthetic;Oncology;Precision;Tools
1
RE, ANGELA
FRONTIERS MEDIA SA
Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy
Review
Ist Italiano Tecnol
LAUSANNE
null
null
Ist Italiano Tecnol
Istituto Italiano di Tecnologia
Re, A (corresponding author), Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy.
null
Re, Angela
9
1
455,238,900,077
Istituto Italiano di Tecnologia
Italy
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Italy
null
null
Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy
2296-634X
Re, A
null
angela.re@iit.it
Designing Precision Tools;nSynthetic Gene Expression Circuits;Oncology
1
J
Cell Biology;Developmental Biology
ANTICANCER DRUGS;ANTITUMOR EFFICACY;AUTOMATED DESIGN;basic biological elements decoupled;biological engineering;brief overview;capabilities;control;DELIVERY;Designing Precision Tools;drug delivery;drug discovery;enabling methodology;engineering;engineering synthetic circuits;enhanced mechanism clarity;functionalized devices;gene expression;gene-based therapy;individual patients;logic;major advances;MAMMALIAN-CELLS;MESSENGER-RNA;natural context;new capabilities;nSynthetic Gene Expression Circuits;Oncology;oncology needs;portability;post-transcriptional/translational;post-translational levels;precision cancer medicine implementations;precision medicine;precision technologies;prospects;rational engineering;remarkable improvements;review;ROBUSTNESS;scalability;sensitivity;significant advancements;specific applications;standardization;successful establishment;synthetic biology;synthetic circuit;synthetic devices;synthetic genetic circuits;T-CELLS;therapeutic technologies;transcriptional;TRANSCRIPTIONAL REGULATORS;tumor cell-;tumor diagnosis;tumor therapy
Re, A
ANTICANCER DRUGS;ANTITUMOR EFFICACY;AUTOMATED DESIGN;biological engineering;DELIVERY;drug delivery;DRUG DISCOVERY;LOGIC;MAMMALIAN-CELLS;MESSENGER-RNA;precision medicine;Synthetic biology;synthetic circuit;T-CELLS;TRANSCRIPTIONAL REGULATORS;tumor diagnosis;tumor therapy
null
[Re, Angela] Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy.
This manuscript has been funded by the Istituto Italiano di Tecnologia.
basic biological elements decoupled;brief overview;capabilities;control;drug delivery;enabling methodology;engineering;engineering synthetic circuits;enhanced mechanism clarity;functionalized devices;gene expression;gene-based therapy;individual patients;major advances;natural context;new capabilities;oncology;oncology needs;portability;post-transcriptional/translational;post-translational levels;precision cancer medicine implementations;precision medicine;precision technologies;prospects;rational engineering;remarkable improvements;review;robustness;scalability;sensitivity;significant advancements;specific applications;standardization;successful establishment;synthetic biology;synthetic devices;synthetic genetic circuits;therapeutic technologies;transcriptional;tumor cell-;tumor diagnosis
10.1002/adfm.201100731;10.1002/anie.200704121;10.1002/cbic.200700478;10.1007/s10875-012-9689-9;10.1016/j.addr.2016.05.004;10.1016/j.addr.2016.08.004;10.1016/j.bioeng.2007.06.001;10.1016/j.biomaterials.2013.11.083;10.1016/j.cbpa.2012.05.179;10.1016/j.cell.2012.05.045;10.1016/j.cell.2013.02.022;10.1016/j.cell.2014.02.022;10.1016/j.cell.2016.01.011;10.1016/j.cell.2017.01.016;10.1016/j.celrep.2013.06.023;10.1016/j.cels.2017.01.003;10.1016/j.chembiol.2009.02.011;10.1016/j.copbio.2015.02.004;10.1016/j.febslet.2012.01.057;10.1016/j.molimm.2014.12.009;10.1016/j.tcb.2012.07.002;10.1016/j.tibtech.2012.11.006;10.1016/j.ymthe.2017.06.014;10.1017/S1355838299990246;10.1021/acs.accounts.6b00386;10.1021/acscentsci.7b00009;10.1021/acssynbio.5b00259;10.1021/acssynbio.7b00105;10.1021/cb800025k;10.1021/co100069t;10.1021/jacs.6b11273;10.1021/sb300107h;10.1021/sb4001273;10.1021/sb500263b;10.1023/B:DRUG.0000026251.00854.77;10.1038/35002131;10.1038/468889a;10.1038/msb.2010.99;10.1038/msb4100168;10.1038/nature04342;10.1038/nature07521;10.1038/nature11149;10.1038/nature11259;10.1038/nature23271;10.1038/nbt.1568;10.1038/nbt.2459;10.1038/nbt.2510;10.1038/nbt.2891;10.1038/nbt.3301;10.1038/nbt.3805;10.1038/nbt1307;10.1038/nbt986;10.1038/nchembio.1551;10.1038/nchembio.1736;10.1038/nchembio719;10.1038/ncomms1157;10.1038/ncomms11658;10.1038/ncomms14633;10.1038/ncomms3393;10.1038/nprot.2011.431;10.1038/nrd3499;10.1038/nrg2697;10.1038/nrm3738;10.1038/nrmicro3239;10.1038/sj.cgt.7700735;10.1039/b706973a;10.1039/c5mb00127g;10.1042/BCJ20160762;10.1046/j.1365-2958.2003.03656.x;10.1056/NEJMoa1106152;10.1073/pnas.0601755103;10.1073/pnas.0703961104;10.1073/pnas.0900267106;10.1073/pnas.1001721107;10.1073/pnas.1015741108;10.1073/pnas.1301301110;10.1073/pnas.1305590110;10.1073/pnas.1311166110;10.1073/pnas.1604391113;10.1080/15476286.2015.1060395;10.1088/1478-3975/aa6f21;10.1093/nar/gkq954;10.1093/nar/gks734;10.1093/nar/gkt520;10.1093/nar/gku1082;10.1093/nar/gku884;10.1093/nar/gkv125;10.1093/nar/gkv287;10.1093/nar/gkv601;10.1093/nar/gkw507;10.1093/nar/gkx008;10.1098/rsif.2014.1000;10.1126/science.1151153;10.1126/science.1172005;10.1126/science.1192128;10.1126/science.1205527;10.1126/science.1214081;10.1126/science.1232758;10.1126/science.282.5387.296;10.1126/science.aac7341;10.1126/scisignal.aab3397;10.1126/scitranslmed.3005568;10.1126/scitranslmed.aaa3519;10.1126/scitranslmed.aaa3601;10.1146/annurev-chembioeng-061312-103351;10.1158/0008-5472.CAN-06-2526;10.1158/0008-5472.CAN-07-5723;10.1158/0008-5472.CAN-13-1365;10.1158/1078-0432.CCR-05-1757;10.1158/1535-7163.MCT-09-0214;10.1159/000341794;10.1371/journal.pcbi.1005198;10.1371/journal.pone.0030940;10.1371/journal.pone.0082742;10.15252/msb.20145299;10.15252/msb.20156777;10.15252/msb.20167265;10.2147/DDDT.S58049;10.3389/fphar.2016.00533;10.4161/rna.27102;[10.1038/NCHEM.2420, 10.1038/nchem.2420];[10.1038/NCHEMBIO.273, 10.1038/nchembio.273];[10.1038/NCHEMBIO.919, 10.1038/nchembio.919];[10.1038/NMAT2614, 10.1038/nmat2614];[10.1038/nnano.2013.44, 10.1038/NNANO.2013.44]
Ist Italiano Tecnol
Re, A
Re, A: Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy
RE, ANGELA
null
126
null
Italy
Ist Italiano Tecnol
Re, Angela
gold, Green Published
ANTICANCER DRUGS;ANTITUMOR EFFICACY;AUTOMATED DESIGN;DELIVERY;LOGIC;MAMMALIAN-CELLS;MESSENGER-RNA;SYNTHETIC BIOLOGY;T-CELLS;TRANSCRIPTIONAL REGULATORS
Re, Angela;
null
Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy
Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy
null
biological engineering;drug delivery;drug discovery;precision medicine;Synthetic biology;synthetic circuits;tumor diagnosis;tumor therapy
null
1998;1999;2000;2003;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
8
Ist Italiano Tecnol, Ctr Sustainable Future Technol, Turin, Italy
Front. Cell. Dev. Biol.
Re, Angela
FRONTIERS MEDIA SA
,;a;advancements;advances;aimed;an;and;applications;as;at;availability;basic;begin;biological;biology;brief;bring;by;cancer;capabilities;cell-;circuits;clarity;construction;context;control;decoupled;delivery;describe;design;devices;diagnosis;diagnostic;drug;elements;enabling;engineering;enhance;enhanced;establishment;expression;focus;for;from;functionalized;gene;gene-based;genetic;have;implementations;improvements;in;individual;its;levels;major;match;mechanism;medicine;methodology;might;natural;needs;new;of;on;oncology;opened;operating;our;overview;patients;portability;post-transcriptional/translational;post-translational;precision;presenting;prospects;rational;remarkable;review;robustness;scalability;sensitivity;significant;some;specific;standardization;streamlines;successful;synthetic;tailor;technologies;the;their;then;therapeutic;therapy;this;through;to;transcriptional;tumor;we;well;which
Ist Italiano Tecnol
Precision medicine in oncology needs to enhance its capabilities to match diagnostic and therapeutic technologies to individual patients. Synthetic biology streamlines the design and construction of functionalized devices through standardization and rational engineering of basic biological elements decoupled from their natural context. Remarkable improvements have opened the prospects for the availability of synthetic devices of enhanced mechanism clarity, robustness, sensitivity, as well as scalability and portability, which might bring new capabilities in precision cancer medicine implementations. In this review, we begin by presenting a brief overview of some of the major advances in the engineering of synthetic genetic circuits aimed to the control of gene expression and operating at the transcriptional, post-transcriptional/translational, and post-translational levels. We then focus on engineering synthetic circuits as an enabling methodology for the successful establishment of precision technologies in oncology. We describe significant advancements in our capabilities to tailor synthetic genetic circuits to specific applications in tumor diagnosis, tumor cell- and gene-based therapy, and drug delivery.
A-4767-2018
ANTICANCER DRUG;ANTITUMOR EFFICACY;AUTOMATED DESIGN;DELIVERY;LOGIC;MAMMALIAN-CELLS;MESSENGER-RNA;TRANSCRIPTIONAL REGULATION;SYNTHETIC BIOLOGY;T-CELLS
1
null
biological engineering;drug delivery;drug discovery;precision medicine;Synthetic biology;synthetic circuit;tumor diagnosis;tumor therapy
9
anticancer drug;ANTITUMOR EFFICACY;AUTOMATED DESIGN;biological engineering;DELIVERY;DRUG-DELIVERY;DRUG DISCOVERY;LOGIC;MAMMALIAN-CELLS;MESSENGER-RNA;precision medicine;Transcriptional regulation;Synthetic biology;SYNTHETIC CIRCUITS;T-CELLS;tumor diagnosis;tumor therapy
WOS:000455238900077
Ist Italiano Tecnol, Turin, Italy
Italy
2,017
null
0000-0002-3179-6967
null
null
English
null
ACCOUNTS CHEM RES;ACS CENTRAL SCI;ACS CHEM BIOL;ACS COMB SCI;ACS SYNTH BIOL;ADV DRUG DELIVER REV;ADV FUNCT MATER;ANGEW CHEM INT EDIT;ANNU REV CHEM BIOMOL;BIOCHEM J;BIOMATERIALS;BIOMOL ENG;CANCER GENE THER;CANCER RES;CELL;CELL REP;CELL SYST;CHEM BIOL;CHEMBIOCHEM;CLIN CANCER RES;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;DRUG DES DEV THER;FEBS LETT;Front Bioeng Biotechnol;FRONT PHARMACOL;INVEST NEW DRUG;J AM CHEM SOC;J CLIN IMMUNOL;J MATER CHEM;J R SOC INTERFACE;MED PRIN PRACT;MOL BIOSYST;MOL CANCER THER;MOL IMMUNOL;MOL MICROBIOL;MOL SYST BIOL;MOL THER;NAT BIOTECHNOL;NAT CHEM;NAT CHEM BIOL;NAT COMMUN;NAT MATER;NAT NANOTECHNOL;NAT PROTOC;NAT REV DRUG DISCOV;NAT REV GENET;NAT REV MICROBIOL;NAT REV MOL CELL BIO;NATURE;NEW ENGL J MED;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS BIOL;PLOS COMPUT BIOL;PLOS ONE;RNA;RNA BIOL;SCI SIGNAL;SCI TRANSL MED;SCIENCE;TRENDS BIOTECHNOL;TRENDS CELL BIOL
Re, Angela
2024-03-11 ER
Afonin, K A;An, W L;Ausländer, S;Bashor, C J;Beisel, C L;Bikard, D;Bonnet, J;Breitling, R;Brewster, R C;Budde, L E;Cameron, D E;Carbonell, P;Cardinale, S;Chandrasekaran, S;Chen, A H;Chen, Y Y;Christen, E H;Collins, I;Comeau, M A;Cora, D;Costales, M G;Courbet, A;Cronin, M;Culler, S J;Danino, T;Davidsohn, N;Di Stasi, A;Douglas, S M;Duong, C P M;Duportet, X;Edwardson, T G W;Elowitz, M;Endo, K;Endy, D;Farokhzad, O C;Fern, J;Ferreira, J P;Ferry, Q R V;Firman, K;Fischbach, M A;Foster, A E;Friedland, A E;Fu, X;Galdzicki, M;Gardner, T S;Gertz, J;Gonzalez-Nicolini, V;Green, A A;Grilly, C;Halman, J R;Hanson, S;Hockenberry, A J;Huh, J H;Isaacs, F J;Jain, K K;Kasap, C;Katuri, J;Ketzer, P;Khalil, A S;Kis, Z;Kloss, C C;Kosuri, S;Kudo, K;Kumaresan, P R;Kwak, H;Lebar, T;Lee, E S;Lee, H K;Lee, N S;Li, Y H;Li, Y Q;Lienert, F;Lim, W A;Los, G V;Lucks, J B;Mohammadi, P;Morel, M;Mukherji, S;Mutalik, V K;Niederholtmeyer, H;Nielsen, A A K;Nissim, L;Ogawa, A;Oishi, M;Qi, L S;Rackham, O;Re, A;Rinaudo, K;Roybal, K T;Rubens, J R;Ryan, P C;Ryu, J;Saito, H;Salis, H M;Sanjana, N E;Schaerli, Y;Schreiber, J;Segall-Shapiro, T H;Shen, S S;Siuti, P;Soundararajan, S;Stoltenburg, R;Stuart, M A C;Tai, W Y;Tian, Y H;Trosset Jean-Yves;Trosset, J Y;Truong, D J J;Vazquez-Anderson, J;Velagapudi, S P;Wagner, H J;Wang, J H;Wang, Y H;Wei, P;Weinberg, B H;Werstuck, G;Wilkie, S;Win, M N;Wroblewska, L;Xie, Z;Yao, Y;Yoo, J W;Zucchelli, S
VH8AQ
Turin, Italy
9
null
1
null
28,894,736
Re, Angela
FRONT CELL DEV BIOL
Turin, Italy
Charpin-El Hamri, G;Fussenegger, M;Xie, M Q;Xue, S;Ye, H F;Yin, J L;Zulewski, H
10.1038/s41551-016-0005
0005
HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
w4z4o2o4d6p5t1n6b4j52484p471f1y2p1x2g43
Self-adjusting synthetic gene circuit for correcting insulin resistance
Swiss Fed Inst Technol
null
Ye, HF (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland.
null
Charpin-El Hamri, Ghislaine;Fussenegger, Martin;Xie, Mingqi;Xue, Shuai;Ye, Haifeng;Yin, Jianli;Zulewski, Henryk
Engineering, Biomedical
European Research Council (ERC) advanced grant [321381]; Cantons of Basel; Cantons of Swiss Confederation within the INTERREG IV A.20 tri-national research program; National Key Research and Development Program of China, Stem Cell and Translational Research [2016YFA0100300]; National Natural Science Foundation of China (NSFC) [31470834, 31522017, 31670869]; Science and Technology Commission of Shanghai Municipality [15QA1401500, 14JC1401700]; Thousand Youth Talents Plan
WOS
Ye, H F
East China Normal Univ, Shanghai, Peoples R China;IUT, Villeurbanne, France;Stadtspital Triemli, Zurich, Switzerland;Swiss Fed Inst Technol, Basel, Switzerland;Univ Basel Hosp, Basel, Switzerland;Univ Basel, Basel, Switzerland
1
circuit;correcting;for;gene;insulin;resistance;self-adjusting;synthetic
3
Ye, Haifeng
NATURE PORTFOLIO
East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China;East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China;IUT, Dept Genie Biol, F-69622 Villeurbanne, France;Stadtspital Triemli, Div Endocrinol & Diabet, Birmensdorferstr 497, CH-8063 Zurich, Switzerland;Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland;Univ Basel Hosp, Div Endocrinol Diabet & Metab, Petersgraben 4, CH-4031 Basel, Switzerland;Univ Basel, Fac Sci, Mattenstr 26, CH-4058 Basel, Switzerland
Article
Swiss Fed Inst Technol
BERLIN
null
null
East China Normal Univ;IUT;Stadtspital Triemli;Swiss Fed Inst Technol;Univ Basel;Univ Basel Hosp
Cantons of Basel;Cantons of Swiss Confederation within the INTERREG IV A.20 tri-national research program;European Research Council (ERC) advanced grant;National Key Research and Development Program of China, Stem Cell and Translational Research;National Natural Science Foundation of China (NSFC);Science and Technology Commission of Shanghai Municipality;Thousand Youth Talents Plan
Ye, HF (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland.
null
Charpin-El Hamri, Ghislaine;Fussenegger, Martin;Xie, Mingqi;Xue, Shuai;Ye, Haifeng;Yin, Jianli;Zulewski, Henryk
76
7
418,850,600,005
Cantons of Basel;Cantons of Swiss Confederation within the INTERREG IV A.20 tri-national research program;European Research Council (ERC) advanced grant [321381];National Key Research and Development Program of China, Stem Cell and Translational Research [2016YFA0100300];National Natural Science Foundation of China (NSFC) [31470834, 31522017, 31670869];Science and Technology Commission of Shanghai Municipality [15QA1401500, 14JC1401700];Thousand Youth Talents Plan
China;France;Switzerland
NATURE BIOMEDICAL ENGINEERING
Switzerland
null
null
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland
2157-846X
Charpin-El Hamri, G;Fussenegger, M;Xie, M Q;Xue, S;Ye, H F;Yin, J L;Zulewski, H
JAN
fussenegger@bsse.ethz.ch;hfye@bio.ecnu.edu.cn
correcting insulin resistance;self-adjusting synthetic gene circuit
7
J
Engineering
acute experimental hyperinsulinaemia;ADIPONECTIN LEVELS;cells;coordinating expression;correcting insulin resistance;different mouse models;engineering synthetic gene circuits;expression;future gene-and cell-based treatments;human ELK1-derived transactivation domain (TetR-Elk1);Hybrid transcription factor;increased blood insulin levels;insulin-resistance syndrome;insulin-sensitizing compound adiponectin;life;MAPK-mediated activation;mitogen-activated protein kinase (MAPK);multifactorial metabolic disorders;opportunities;pathologic markers;PATHWAY;reprogram mammalian cell activities;reversible expression;self-adjusting synthetic gene circuit;self-sufficiently;sophisticated genetic devices;synthetic biology;synthetic insulin-sensing designer circuit;synthetic insulin-sensitive transcriptioncontrol device;synthetic TetR-ELK1-specific promoters;TetR;tetracycline repressor;therapeutic transgenes;tools
Ye, H F
ADIPONECTIN LEVELS;CELLS;EXPRESSION;LIFE
null
[Ye, Haifeng; Xie, Mingqi; Zulewski, Henryk; Fussenegger, Martin] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland. [Ye, Haifeng; Xue, Shuai; Yin, Jianli] East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China. [Ye, Haifeng; Xue, Shuai; Yin, Jianli] East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China. [Charpin-El Hamri, Ghislaine] IUT, Dept Genie Biol, F-69622 Villeurbanne, France. [Zulewski, Henryk] Univ Basel Hosp, Div Endocrinol Diabet & Metab, Petersgraben 4, CH-4031 Basel, Switzerland. [Zulewski, Henryk] Stadtspital Triemli, Div Endocrinol & Diabet, Birmensdorferstr 497, CH-8063 Zurich, Switzerland. [Fussenegger, Martin] Univ Basel, Fac Sci, Mattenstr 26, CH-4058 Basel, Switzerland.
We thank T. Abel for providing the pTetR-ELK1 (MKp37) plasmid, B. Geering for providing human serum from healthy individuals, Y. Lai for providing the DyLight 800-labelled goat anti-mouse IgG, B.M. Lang and L. Scheller for assistance with the statistical analyses and M. Daoud-El Baba for skilful assistance with the animal study. This work was supported by a European Research Council (ERC) advanced grant (no. 321381), the Cantons of Basel and the Swiss Confederation within the INTERREG IV A.20 tri-national research program and the Gutenberg Chair (awarded to M.F.). This work was also supported by the National Key Research and Development Program of China, Stem Cell and Translational Research (no. 2016YFA0100300), the National Natural Science Foundation of China (NSFC; nos 31470834, 31522017 and 31670869), the Science and Technology Commission of Shanghai Municipality (nos 15QA1401500 and 14JC1401700) and Thousand Youth Talents Plan (awarded to H.Y.).
acute experimental hyperinsulinaemia;coordinating expression;different mouse models;engineering synthetic gene circuits;expression;future gene-and cell-based treatments;human ELK1-derived transactivation domain (TetR-Elk1);hybrid transcription factor;increased blood insulin levels;insulin-resistance syndrome;insulin-sensitizing compound adiponectin;MAPK-mediated activation;mitogen-activated protein kinase (MAPK);multifactorial metabolic disorders;opportunities;pathologic markers;pathway;reprogram mammalian cell activities;reversible expression;self-adjusting synthetic gene circuit;self-sufficiently;sophisticated genetic devices;synthetic biology;synthetic insulin-sensing designer circuit;synthetic insulin-sensitive transcriptioncontrol device;synthetic TetR-ELK1-specific promoters;TetR;tetracycline repressor;therapeutic transgenes;tools
10.1001/jama.2009.976;10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S;10.1002/anie.201412204;10.1007/BF00280883;10.1016/j.biomaterials.2013.09.071;10.1016/j.cbpa.2013.10.006;10.1016/j.cbpa.2015.05.021;10.1016/j.cell.2012.02.017;10.1016/j.cell.2013.01.041;10.1016/j.cmet.2011.07.015;10.1016/j.coi.2015.06.015;10.1016/j.copbio.2015.01.010;10.1016/j.jconrel.2010.11.016;10.1016/j.jhep.2016.03.020;10.1016/j.jmb.2010.03.062;10.1016/j.molcel.2014.06.007;10.1016/j.ymeth.2012.01.005;10.1016/S0140-6736(07)61721-8;10.1016/S0140-6736(16)00618-8;10.1016/S0303-7207(01)00674-8;10.1016/S0378-1119(01)00824-1;10.1038/81208;10.1038/msb.2013.48;10.1038/nature12656;10.1038/nbt0602-592;10.1038/nbt1021;10.1038/ng.343;10.1038/nrg3094;10.1038/nrm.2016.10;10.1038/nrm3072;10.1073/pnas.1216801110;10.1073/pnas.1508521112;10.1093/nar/gkt405;10.1126/science.1206843;10.1136/bmj.d1309;10.1136/bmj.f5934;10.1172/JCI29103;10.1210/jc.86.5.1930;10.1530/JME-11-0022;10.2144/000112002;10.2337/db12-0935;10.3945/ajcn.2009.28449C
Swiss Fed Inst Technol
Charpin-El Hamri, G;Fussenegger, M;Xie, M Q;Xue, S;Ye, H F;Yin, J L;Zulewski, H
Ye, H F: Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland
null
14JC1401700;15QA1401500;2016YFA0100300;31470834;31522017;31670869;321381
42
null
Switzerland
East China Normal Univ;IUT;Stadtspital Triemli;Swiss Fed Inst Technol;Univ Basel;Univ Basel Hosp
Ye, Haifeng
Green Accepted
ADIPONECTIN LEVELS;CELLS;EXPRESSION;LIFE
Ye, Haifeng; Xie, Mingqi; Xue, Shuai; Charpin-El Hamri, Ghislaine; Yin, Jianli; Zulewski, Henryk; Fussenegger, Martin;
null
East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China;East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China;IUT, Dept Genie Biol, F-69622 Villeurbanne, France;Stadtspital Triemli, Div Endocrinol & Diabet, Birmensdorferstr 497, CH-8063 Zurich, Switzerland;Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland;Univ Basel Hosp, Div Endocrinol Diabet & Metab, Petersgraben 4, CH-4031 Basel, Switzerland;Univ Basel, Fac Sci, Mattenstr 26, CH-4058 Basel, Switzerland
East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Dongchuan Rd 500, Shanghai 200241, Peoples R China;East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China;IUT, Dept Genie Biol, F-69622 Villeurbanne, France;Stadtspital Triemli, Div Endocrinol & Diabet, Birmensdorferstr 497, CH-8063 Zurich, Switzerland;Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland;Univ Basel Hosp, Div Endocrinol Diabet & Metab, Petersgraben 4, CH-4031 Basel, Switzerland;Univ Basel, Fac Sci, Mattenstr 26, CH-4058 Basel, Switzerland
null
null
1
1985;1998;2000;2001;2002;2004;2005;2006;2007;2009;2010;2011;2012;2013;2014;2015;2016
72
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland
Nat. Biomed. Eng
Fussenegger, Martin
NATURE PORTFOLIO
(MAPK);(TetR-Elk1);,;a;activation;activities;acute;adiponectin;and;assembled;be;between;biology;blood;by;can;cell;cell-based;circuit;circuits;compound;consisting;coordinate;coordinating;Correspondingly;demonstrate;designed;designer;device;devices;different;disorders;distinguished;domain;ELK1-derived;engineering;experimental;expression;factor;fine-tuned;for;from;functionally;fused;future;gene;gene-and;genetic;here;human;hybrid;hyperinsulinaemia;in;increased;insulin;insulin-resistance;insulin-sensing;insulin-sensitive;insulin-sensitizing;kinase;levels;mammalian;MAPK-mediated;Markers;may;metabolic;mitogen-activated;models;mouse;multifactorial;of;opportunities;pathologic;pathway;physiological;produce;promoters;protein;provide;repressor;reprogram;reverse;reversed;reversible;rewiring;self-adjusting;self-sufficiently;sense;signalling;sophisticated;syndrome;synthetic;TetR;TetR-ELK1-specific;tetracycline;that;the;therapeutic;to;tools;transactivation;transcription;transcriptioncontrol;transgenes;treatments;using;we
Swiss Fed Inst Technol
Sophisticated genetic devices can be assembled to reprogram mammalian cell activities using tools from synthetic biology. Here, we demonstrate that a self-adjusting synthetic gene circuit can be designed to sense and reverse the insulin-resistance syndrome in different mouse models. By functionally rewiring the mitogen-activated protein kinase (MAPK) signalling pathway to produce MAPK-mediated activation of a hybrid transcription factor consisting of the tetracycline repressor, TetR, fused to the human ELK1-derived transactivation domain (TetR-Elk1), we assembled a synthetic insulin-sensitive transcriptioncontrol device that self-sufficiently distinguished between physiological and increased blood insulin levels and correspondingly fine-tuned the reversible expression of therapeutic transgenes from synthetic TetR-ELK1-specific promoters. In acute experimental hyperinsulinaemia, the synthetic insulin-sensing designer circuit reversed the insulin-resistance syndrome by coordinating expression of the insulin-sensitizing compound adiponectin. Engineering synthetic gene circuits to sense pathologic markers and coordinate the expression of therapeutic transgenes may provide opportunities for future gene-and cell-based treatments of multifactorial metabolic disorders.
null
ADIPONECTIN LEVELS;CELLS;EXPRESSION;LIFE
7
null
null
9
ADIPONECTIN LEVELS;CELLS;EXPRESSION;LIFE
WOS:000418850600005
East China Normal Univ, Shanghai, Peoples R China;IUT, Villeurbanne, France;Stadtspital Triemli, Zurich, Switzerland;Swiss Fed Inst Technol, Basel, Switzerland;Univ Basel Hosp, Basel, Switzerland;Univ Basel, Basel, Switzerland
China;France;Switzerland
2,017
null
0000-0002-5482-8116
null
null
English
null
AM J CLIN NUTR;ANGEW CHEM INT EDIT;BIOMATERIALS;BIOTECHNIQUES;BMJ;BMJ-BRIT MED J;CELL;CELL METAB;CURR OPIN BIOTECH;CURR OPIN CHEM BIOL;CURR OPIN IMMUNOL;DIABETES;DIABETIC MED;DIABETOLOGIA;GENE;J CLIN ENDOCR METAB;J CLIN INVEST;J CONTROL RELEASE;J HEPATOL;J MOL BIOL;J MOL ENDOCRINOL;JAMA-J AM MED ASSOC;LANCET;METHODS;MOL CELL;MOL CELL ENDOCRINOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT GENET;NAT REV GENET;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;SCIENCE
Charpin-El Hamri, Ghislaine;Fussenegger, Martin;Xie, Mingqi;Xue, Shuai;Ye, Haifeng;Yin, Jianli;Zulewski, Henryk
2024-03-11 ER
Alberti, K G M M;Altarejos, J Y;Ausländer, D;Bacchus, W;Bai, P;Bornfeldt, K E;Christensen, R;Folcher, M;Fussenegger, M;Gao, H;Ge, H F;Gloy, V L;Heng, B C;Jacob, K K;Johnson, A M F;Keeley, M B;Kemmer, C;Kim, T;Kojima, R;Lathuilière, A;Li, S S;Loke Yoon Kong;Matthews, D R;Mátés, L;Okada-Iwabu, M;Prentki, M;Ruder, W C;Samuel, V T;Schlatter, S;Siddle, K;Simonsen, J L;Slomovic, S;Trounson, A;Weber, W;Weyer, C;Wieland, M;Wu, C Y;Ye, H F;Zhou, B;Ziemke, F
FR1TQ
Basel, Switzerland
85
null
6
null
28,480,128
Charpin-El Hamri, Ghislaine;Fussenegger, Martin;Xie, Mingqi;Xue, Shuai;Ye, Haifeng;Yin, Jianli;Zulewski, Henryk
NAT BIOMED ENG
Basel, Switzerland;Shanghai, Peoples R China;Villeurbanne, France;Zurich, Switzerland
Agnew, C;Brady, R L;Burley, G A;Burton, N;de Ornellas, S;Eperon, I C;Eperon, L P;Reichenbach, L F;Sobri, A A;Zaccai, N R
10.1016/j.chempr.2016.11.009
null
50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
2s2z14p113x2y5j7041574q4z5v4t3m4d705l1z
Structural Basis of the Mispairing of an Artificially Expanded Genetic Information System
Univ Strathclyde
null
Brady, RL (corresponding author), Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England.;Burley, GA (corresponding author), Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland.;Eperon, IC (corresponding author), Univ Leicester, Dept Mol & Cellular Biol, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England.
null
Agnew, Christopher;Brady, R Leo;Burley, Glenn A;Burton, Nicholas;de Ornellas, Sara;Eperon, Ian C;Eperon, Lucy P;Reichenbach, Linus F;Sobri, Ahmad Ahmad;Zaccai, Nathan R
Chemistry, Multidisciplinary
Biotechnology and Biological Sciences Research Council [BB/J020087/1, BB/J02080X/1]; Leverhulme Trust [RPG-2014-001]; Biotechnology and Biological Sciences Research Council [BB/J020087/1, BB/J02080X/1] Funding Source: researchfish; BBSRC [BB/J020087/1, BB/J02080X/1] Funding Source: UKRI
WOS
Brady, R L;Burley, G A;Eperon, I C
Univ Bristol, Avon, England;Univ Leicester, Leics, England;Univ Strathclyde, Lanark, Scotland
1
an;Artificially;Basis;Expanded;genetic;Information;Mispairing;of;structural;system;the
1
Burley, Glenn;De Ornellas, Sara;Zaccai, Nathan
CELL PRESS
Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England;Univ Leicester, Dept Mol & Cellular Biol, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England;Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland;Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland.; Brady, RL (corresponding author), Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England.; Eperon, IC (corresponding author), Univ Leicester, Dept Mol & Cellular Biol, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England
Article
Univ Bristol;Univ Leicester;Univ Strathclyde
CAMBRIDGE
null
null
Univ Bristol;Univ Leicester;Univ Strathclyde
BBSRC;Biotechnology and Biological Sciences Research Council;Leverhulme Trust
Burley, GA (corresponding author), Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland.; Brady, RL (corresponding author), Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England.; Eperon, IC (corresponding author), Univ Leicester, Dept Mol & Cellular Biol, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England.
958
Agnew, Christopher;Brady, R Leo;Burley, Glenn A;Burton, Nicholas;de Ornellas, Sara;Eperon, Ian C;Eperon, Lucy P;Reichenbach, Linus F;Sobri, Ahmad Ahmad;Zaccai, Nathan R
18
3
389,801,600,014
BBSRC [BB/J020087/1, BB/J02080X/1] Funding Source: UKRI;Biotechnology and Biological Sciences Research Council [BB/J020087/1, BB/J02080X/1];Biotechnology and Biological Sciences Research Council [BB/J020087/1, BB/J02080X/1] Funding Source: researchfish;Leverhulme Trust [RPG-2014-001]
UK
CHEM
UK
null
null
Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
2451-9294
Agnew, C;Brady, R L;Burley, G A;Burton, N;de Ornellas, S;Eperon, I C;Eperon, L P;Reichenbach, L F;Sobri, A A;Zaccai, N R
DEC 8
eci@le.ac.uk;glenn.burley@strath.ac.uk;l.brady@bristol.ac.uk
Expanded Genetic Information System;Mispairing;structural Basis
10
J
Chemistry
7.8;ALPHABET;B-DNA DODECAMER;CLICK CHEMISTRY;conversion;development;DNA duplexes;double-hydrogen-bonded;Expanded Genetic Information System;EXPANSION;functional methods;G-C base pair;G-Z mispair;HYDROGEN-BONDING PATTERN;loss;mechanisms;Mispairing;mutation;need;next-generation synthetic genetic base pairs;NUCLEIC-ACID;P-Z;PAIR SYSTEMS;PCR AMPLIFICATION;PCR results;pH;pH 7.8;pH dependent;plastic;relative;replication;RNA;ROBUST;slipped'' pair;STRUCTURAL BASIS;study;synthetic genetic information;synthetic nucleotide P pairs;triple-hydrogen-bonded Z-G pair;unique hydrogen-bond arrangement;viaG-Z mispairing;Watson-Crick base pairs;Z
Reichenbach, L F
ALPHABET;B-DNA DODECAMER;CLICK CHEMISTRY;EXPANSION;HYDROGEN-BONDING PATTERN;NUCLEIC-ACID;PAIR SYSTEMS;PCR AMPLIFICATION;REPLICATION;RNA
946
[Reichenbach, Linus F.; de Ornellas, Sara; Burley, Glenn A.] Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland. [Sobri, Ahmad Ahmad; Zaccai, Nathan R.; Agnew, Christopher; Burton, Nicholas; Brady, R. Leo] Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England. [Eperon, Lucy P.; Eperon, Ian C.] Univ Leicester, Dept Mol & Cellular Biol, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England.
This work was supported by the Biotechnology and Biological Sciences Research Council (BB/J020087/1 to R.L.B. and G.A.B.; BB/J02080X/1 to G.A.B. and E.C.I.) and the Leverhulme Trust (RPG-2014-001 to E.C.I. and G.A.B.). We thank Dr. Sharon Kelly (University of Glasgow) for measurement of the CD spectra. We also thank Diamond Light Source for beamtime (proposals mx8922 and mx12342) and the staff of beamlines I02, I03, and I04-1 for assistance with crystal testing and data collection.
7.8;conversion;development;DNA duplexes;double-hydrogen-bonded;functional methods;G-C base pair;G-Z mispair;loss;mechanisms;mutation;need;next-generation synthetic genetic base pairs;P-Z;PCR results;pH;pH 7.8;pH dependent;plastic;relative;robust;slipped'' pair;study;synthetic genetic information;synthetic nucleotide P pairs;triple-hydrogen-bonded Z-G pair;unique hydrogen-bond arrangement;viaG-Z mispairing;Watson-Crick base pairs;Z
10.1002/anie.200905173;10.1002/anie.201502890;10.1007/978-1-4020-6316-9_4;10.1016/j.str.2003.11.008;10.1021/ar200257x;10.1021/ar200262x;10.1021/bi00532a002;10.1021/bi201710q;10.1021/bi501534x;10.1021/ja073830m;10.1021/ja204910n;10.1021/ja207907d;10.1021/ja3125299;10.1021/ja408814g;10.1021/jacs.5b02251;10.1021/jacs.5b03482;10.1021/jo300230z;10.1021/sb500268n;10.1038/171737a0;10.1038/171964b0;10.1038/287755a0;10.1038/2930;10.1038/nature13314;10.1038/nbt.2556;10.1038/nprot.2008.104;10.1038/nrg1637;10.1039/b605414e;10.1039/b811159f;10.1039/c2cc36293g;10.1073/pnas.1205176109;10.1073/pnas.1311778111;10.1073/pnas.78.4.2179;10.1073/pnas.94.20.10506;10.1074/jbc.274.35.24749;10.1093/nar/gkl633;10.1093/nar/gkm395;10.1093/nar/gkn956;10.1093/nar/gkp026;10.1093/nar/gkr1068;10.1093/nar/gks322;10.1093/nar/gkt738;10.1093/nar/gku715;10.1093/nar/gkv638;10.1107/S0021889807021206;10.1107/S0907444910045749;10.1146/annurev.biochem.69.1.497;10.2183/pjab.88.345;[10.1038/NCHEM.1117, 10.1038/nchem.1117]
Univ Strathclyde
Agnew, C;Brady, R L;Burley, G A;Burton, N;de Ornellas, S;Eperon, I C;Eperon, L P;Reichenbach, L F;Sobri, A A;Zaccai, N R
Reichenbach, L F: Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
Burley, Glenn;Burton, Nick;De Ornellas, Sara;Eperon, Ian C.
BB/J020087/1;BB/J02080X/1;RPG-2014-001
51
null
UK
Univ Bristol;Univ Leicester;Univ Strathclyde
Reichenbach, Linus F
Green Submitted, hybrid, Green Accepted
ALPHABET;B-DNA DODECAMER;CLICK CHEMISTRY;EXPANSION;HYDROGEN-BONDING PATTERN;NUCLEIC-ACID;PAIR SYSTEMS;PCR AMPLIFICATION;REPLICATION;RNA
Reichenbach, Linus F.; Sobri, Ahmad Ahmad; Zaccai, Nathan R.; Agnew, Christopher; Burton, Nicholas; Eperon, Lucy P.; de Ornellas, Sara; Eperon, Ian C.; Brady, R. Leo; Burley, Glenn A.;
null
Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England;Univ Leicester, Dept Mol & Cellular Biol, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England;Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England;Univ Leicester, Dept Mol & Cellular Biol, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England;Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
null
null
6
1953;1980;1981;1982;1987;1997;1998;1999;2000;2003;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015
16
Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England;Univ Leicester, Dept Mol & Cellular Biol, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg,Lancaster Rd, Leicester LE1 7RH, Leics, England;Univ Strathclyde, Dept Pure & Appl Chem, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
Chem
Burley, Glenn A
CELL PRESS
";,;7.8;;;a;above;and;arrangement;at;base;both;by;conversion;dependent;development;DNA;double-hydrogen-bonded;duplexes;elucidate;evidence;for;forms;functional;G-C;G-Z;genetic;here;highlights;hydrogen-bond;in;information;into;is;it;loss;mechanisms;methods;mispair;mispairing;mutation;naturally;need;next-generation;nucleotide;occurring;occurs;of;P;P-Z;pair;pairs;PCR;pH;plastic;relative;remarkably;results;robust;show;slipped'';spectroscopic;structural;study;synthetic;that;the;this;through;to;triple-hydrogen-bonded;unique;viaG-Z;Watson-Crick;we;when;with;within;Z;Z-G
Univ Bristol;Univ Leicester;Univ Strathclyde
Relative to naturally occurring Watson-Crick base pairs, the synthetic nucleotide P pairs with Z within DNA duplexes through a unique hydrogen-bond arrangement. The loss of this synthetic genetic information by PCR results in the conversion of P-Z into a G-C base pair. Here, we show structural and spectroscopic evidence that the loss of this synthetic genetic information occurs viaG-Z mispairing. Remarkably, the G-Z mispair is both plastic and pH dependent; it forms a double-hydrogen-bonded "slipped'' pair at pH 7.8 and a triple-hydrogen-bonded Z-G pair when the pH is above 7.8. This study highlights the need for robust structural and functional methods to elucidate the mechanisms of mutation in the development of next-generation synthetic genetic base pairs.
AAV-8541-2021;C-7064-2013;E-8799-2011;M-2412-2014
ALPHABET;B-DNA DODECAMER;CLICK CHEMISTRY;EXPANSION;HYDROGEN-BONDING PATTERN;NUCLEIC-ACIDS;PAIR SYSTEMS;PCR AMPLIFICATION;REPLICATION;RNA
0
null
null
13
ALPHABET;B-DNA DODECAMER;CLICK CHEMISTRY;EXPANSION;HYDROGEN-BONDING PATTERN;NUCLEIC-ACIDS;PAIR SYSTEMS;PCR AMPLIFICATION;REPLICATION;RNA
WOS:000389801600014
Univ Bristol, Avon, England;Univ Leicester, Leics, England;Univ Strathclyde, Lanark, Scotland
UK
2,016
null
0000-0002-1476-2044;0000-0002-4896-113X;0000-0002-7333-5456
null
null
English
null
ACCOUNTS CHEM RES;ACS SYNTH BIOL;ACTA CRYSTALLOGR D;ANGEW CHEM INT EDIT;ANNU REV BIOCHEM;BIOCHEMISTRY-US;CHEM COMMUN;J AM CHEM SOC;J APPL CRYSTALLOGR;J BIOL CHEM;J ORG CHEM;NAT BIOTECHNOL;NAT CHEM;NAT PROTOC;NAT REV GENET;NAT STRUCT BIOL;NATO SCI SER II-MATH;NATURE;NUCLEIC ACIDS RES;P JPN ACAD B-PHYS;P NATL ACAD SCI USA;P NATL ACAD SCI-BIOL;PYMOL MOL GRAPH SYST;STRUCTURE
Agnew, Christopher;Brady, R Leo;Burley, Glenn A;Burton, Nicholas;de Ornellas, Sara;Eperon, Ian C;Eperon, Lucy P;Reichenbach, Linus F;Sobri, Ahmad Ahmad;Zaccai, Nathan R
2024-03-11 ER
[Anonymous];Benner, S A;Derose, E F;Dhami, K;Drew, H R;Emsley P.;Georgiadis, M M;Geyer, C R;Guckian, K M;Hirao, I;Hodson, M J;Hunter W. N.;Ishizuka, T;Kaul, C;Kim, H J;Kimoto, M;Kool, E T;Krishnamurthy, R;Kunkel, T A;Kypr, J;Leal, N A;Leslie, A G W;Li, L J;Liu, J;Lu, X J;Malyshev, D A;Mccoy, A J;Moran, S;Patel, D J;Renciuk, D;Sefah, K;Seo, Y J;Sheng, P P;Someya, T;Szulik, M W;Watson, J D;Wilcox, J L;Wing, R;Winn, M D;Yamashige, R;Yang, Z Y;Zhang, L Q
EE7MH
Avon, England.;Lanark, Scotland.;Leics, England
16
null
3
null
null
Agnew, Christopher;Brady, R Leo;Burley, Glenn A;Burton, Nicholas;de Ornellas, Sara;Eperon, Ian C;Eperon, Lucy P;Reichenbach, Linus F;Sobri, Ahmad Ahmad;Zaccai, Nathan R
CHEM-US
Avon, England;Lanark, Scotland;Leics, England
Inouye, S;Suzuki, T
10.1016/j.pep.2016.08.006
null
525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
6e185r3v1l2d1k1s4035e2f6r3v2g5u3x6r3bz
Protein expression of preferred human codon-optimized <i>Gaussia</i> luciferase genes with an artificial open-reading frame in mammalian and bacterial cells
JNC Co
null
Inouye, S (corresponding author), JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan.
null
Inouye, Satoshi;Suzuki, Takahiro
Biochemical Research Methods;Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
JSPS KAKENHI Grant [26462828]; Research Foundation for Aichi-Gakuin University; Grants-in-Aid for Scientific Research [26462828] Funding Source: KAKEN
WOS
Inouye, S
Aichi Gakuin Univ, Aichi, Japan;JNC Co, Kanagawa, Japan
128
<i>Gaussia</i>;an;and;Artificial;Bacterial;Cells;codon-optimized;expression;frame;genes;human;in;luciferase;mammalian;of;open-reading;preferred;protein;with
1
Inouye, Satoshi
ACADEMIC PRESS INC ELSEVIER SCIENCE
Aichi Gakuin Univ, Sch Dent, Dept Biochem, Chikusa Ku, 1-100 Kusumoto Cho, Nagoya, Aichi 4648650, Japan;JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan
Article
JNC Co
SAN DIEGO
null
null
Aichi Gakuin Univ;JNC Co
Grants-in-Aid for Scientific Research;JSPS KAKENHI Grant;Research Foundation for Aichi-Gakuin University
Inouye, S (corresponding author), JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan.
100
Inouye, Satoshi;Suzuki, Takahiro
21
2
384,629,700,014
Grants-in-Aid for Scientific Research [26462828] Funding Source: KAKEN;JSPS KAKENHI Grant [26462828];Research Foundation for Aichi-Gakuin University
Japan
PROTEIN EXPRESSION AND PURIFICATION
Japan
null
null
JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan
1046-5928
Inouye, S;Suzuki, T
DEC
sinouye@jnc-corp.co.jp
artificial open-reading frame;bacterial cells;preferred human codon-optimized <i>Gaussia</i> luciferase genes;protein expression
2
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
60% activities;65% GC content;ALGA CHLAMYDOMONAS-REINHARDTII;artificial open-reading frame;bacterial cells;C 2016 Elsevier Inc;Codon optimization;complete preferred human codons;EpGLuc;ESCHERICHIA-COLI;hGLuc;human codon-optimized Gaussia luciferase gene (hGLuc);IN-VIVO;KpGLuc;KpGLuc);Luciferase;mammalian cells;NANOKAZ;OPLOPHORUS LUCIFERASE;pGLuc;Photoprotein;preferred human codon-optimized <i>Gaussia</i> luciferase genes;PRINCEPS;PROTEIN EXPRESSION;protein expressions;reporter gene;rights reserved;secretion;similar protein expression levels;SUBSTRATE;synthetic gene;three preferred human codon-optimized Gaussia luciferase genes (pGLuc;two synthetic genes;wGLuc;wild-type Gaussia luciferase gene (wGLuc)
Inouye, S
ALGA CHLAMYDOMONAS-REINHARDTII;Codon optimization;ESCHERICHIA-COLI;IN-VIVO;Luciferase;NANOKAZ;OPLOPHORUS LUCIFERASE;Photoprotein;PRINCEPS;reporter gene;SECRETION;SUBSTRATE;Synthetic gene
93
[Inouye, Satoshi] JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan. [Suzuki, Takahiro] Aichi Gakuin Univ, Sch Dent, Dept Biochem, Chikusa Ku, 1-100 Kusumoto Cho, Nagoya, Aichi 4648650, Japan.
This work was supported in part by grants from JSPS KAKENHI Grant Number 26462828 (T.S.), and Research Foundation for Aichi-Gakuin University (T.S.).
60% activities;65% GC content;artificial open-reading frame;bacterial cells;complete preferred human codons;EpGLuc;hGLuc;human codon-optimized Gaussia luciferase gene (hGLuc);KpGLuc;KpGLuc);mammalian cells;pGLuc;protein expression;protein expressions;similar protein expression levels;three preferred human codon-optimized Gaussia luciferase genes (pGLuc;two synthetic genes;wGLuc;wild-type Gaussia luciferase gene (wGLuc)
10.1007/978-1-62703-718-1_6;10.1007/s00294-008-0189-7;10.1007/s00438-008-0352-3;10.1016/j.ab.2011.03.039;10.1016/j.bbrc.2007.10.152;10.1016/j.bbrc.2008.08.149;10.1016/j.bbrc.2013.06.026;10.1016/j.bbrc.2014.06.140;10.1016/j.febslet.2007.08.036;10.1016/j.jbiosc.2014.08.006;10.1016/j.pep.2009.01.010;10.1016/j.pep.2012.12.006;10.1016/j.pep.2015.02.002;10.1016/j.ymthe.2004.10.016;10.1038/nbt984;10.1093/bioinformatics/btu192;10.1093/nar/gkm219;10.1128/AEM.06670-11;10.1128/IAI.00223-09;10.1371/journal.pone.0017596;10.1371/journal.pone.0025243;10.4161/viru.3.1.18799
JNC Co
Inouye, S;Suzuki, T
Inouye, S: JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan
null
26462828
23
null
Japan
Aichi Gakuin Univ;JNC Co
Inouye, Satoshi
null
ALGA CHLAMYDOMONAS-REINHARDTII;ESCHERICHIA-COLI;IN-VIVO;NANOKAZ;OPLOPHORUS LUCIFERASE;PRINCEPS;SECRETION;SUBSTRATE
Inouye, Satoshi; Suzuki, Takahiro;
null
Aichi Gakuin Univ, Sch Dent, Dept Biochem, Chikusa Ku, 1-100 Kusumoto Cho, Nagoya, Aichi 4648650, Japan;JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan
Aichi Gakuin Univ, Sch Dent, Dept Biochem, Chikusa Ku, 1-100 Kusumoto Cho, Nagoya, Aichi 4648650, Japan;JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan
1096-0279
Codon optimization;Luciferase;Photoprotein;reporter gene;Synthetic gene
null
1999;2004;2005;2007;2008;2009;2011;2012;2013;2014;2015
6
JNC Co, Yokohama Res Ctr, Kanazawa Ku, 5-1 Okawa, Yokohama, Kanagawa 2368605, Japan
Protein Expr. Purif.
Suzuki, Takahiro
ACADEMIC PRESS INC ELSEVIER SCIENCE
(hGLuc);(pGLuc;(wGLuc);,;60%;65%;;;activities;affect;an;and;approximately;artificial;bacterial;by;cells;characterized;codon-optimized;codons;comparing;complete;containing;content;did;EpGLuc;expression;expressions;frame;Gaussia;GC;gene;genes;had;have;hGLuc;however;human;in;KpGLuc;KpGLuc);levels;luciferase;mammalian;not;of;open-reading;pGLuc;preferred;protein;same;showed;similar;synthetic;the;them;they;those;three;to;two;were;wGLuc;wild-type;with
JNC Co
The protein expressions of three preferred human codon-optimized Gaussia luciferase genes (pGLuc, EpGLuc, and KpGLuc) were characterized in mammalian and bacterial cells by comparing them with those of wild-type Gaussia luciferase gene (wGLuc) and human codon-optimized Gaussia luciferase gene (hGLuc). Two synthetic genes of EpGLuc and KpGLuc containing the complete preferred human codons have an artificial open-reading frame; however, they had the similar protein expression levels to those of pGLuc and hGLuc in mammalian cells. In bacterial cells, the protein expressions of pGLuc, EpGLuc, and KpGLuc with approximately 65% GC content were the same and showed approximately 60% activities of wGLuc and hGLuc. The artificial open-reading frame in EpGLuc and KpGLuc did not affect the protein expression in mammalian and bacterial cells.
null
ALGA CHLAMYDOMONAS-REINHARDTII;ESCHERICHIA-COLI;IN-VIVO;NANOKAZ;OPLOPHORUS LUCIFERASE;PRINCEPS;SECRETION;SUBSTRATE
1
null
Codon optimization;Luciferase;Photoprotein;reporter gene;Synthetic gene
8
ESCHERICHIA-COLI;ALGA CHLAMYDOMONAS-REINHARDTII;Codon optimization;IN-VIVO;Luciferase;NANOKAZ;OPLOPHORUS LUCIFERASE;Photoprotein;PRINCEPS;reporter gene;SECRETION;SUBSTRATE;Synthetic gene
WOS:000384629700014
Aichi Gakuin Univ, Aichi, Japan;JNC Co, Kanagawa, Japan
Japan
2,016
null
0000-0001-8732-7839
null
null
English
null
ANAL BIOCHEM;APPL ENVIRON MICROB;BIOCHEM BIOPH RES CO;BIOINFORMATICS;CURR GENET;FEBS LETT;INFECT IMMUN;J BIOSCI BIOENG;METHODS MOL BIOL;MOL GENET GENOMICS;MOL THER;NAT BIOTECHNOL;NUCLEIC ACIDS RES;PLOS ONE;PROTEIN EXPRES PURIF;VIRULENCE
Inouye, Satoshi;Suzuki, Takahiro
2024-03-11 ER
Bryan, B J;Chin, J X;Donat, S;Enjalbert, B;Fath, S;Inouye, S;Puigbò, P;Qing, G L;Ruecker, O;Shao, N;Suzuki, T;Tannous, B A;Wille, T;Yarimizu, T
DX8HW
Kanagawa, Japan
8
null
2
null
27,506,135
Inouye, Satoshi;Suzuki, Takahiro
PROTEIN EXPRES PURIF
Aichi, Japan;Kanagawa, Japan
Arter, M;Benenson, Y;Haefliger, B;Lapique, N;Schreiber, J
10.15252/msb.20167265
899
111 RIVER ST, HOBOKEN 07030-5774, NJ USA
1t1m1i364w2q1c362h484u65s4lf6c445k3d42
Model-guided combinatorial optimization of complex synthetic gene networks
Swiss Fed Inst Technol
null
Benenson, Y (corresponding author), Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
null
Arter, Meret;Benenson, Yaakov;Haefliger, Benjamin;Lapique, Nicolas;Schreiber, Joerg
Biochemistry & Molecular Biology
Swiss National Science Foundation; NCCR "Molecular Systems Engineering"; ETH Zurich
WOS
Benenson, Y
Swiss Fed Inst Technol, Basel, Switzerland
12
Combinatorial;complex;gene;model-guided;networks;of;optimization;synthetic
1
Lapique, Nicolas
WILEY
Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
Article
Swiss Fed Inst Technol
HOBOKEN
null
null
Swiss Fed Inst Technol
ETH Zurich;NCCR "Molecular Systems Engineering";Swiss National Science Foundation
Benenson, Y (corresponding author), Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
null
Arter, Meret;Benenson, Yaakov;Haefliger, Benjamin;Lapique, Nicolas;Schreiber, Joerg
21
1
400,097,600,010
ETH Zurich;NCCR "Molecular Systems Engineering";Swiss National Science Foundation
Switzerland
MOLECULAR SYSTEMS BIOLOGY
Switzerland
null
null
Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
1744-4292
Arter, M;Benenson, Y;Haefliger, B;Lapique, N;Schreiber, J
DEC
kobi.benenson@bsse.ethz.ch
complex synthetic gene networks;model-guided combinatorial optimization
5
J
Biochemistry & Molecular Biology
AUTOMATED DESIGN;biosensor integration;biosensor reprogramming;combination;complex gene networks;complex synthetic gene networks;complex three-gene circuit;CONSTRUCTION;data;detailed mechanistic interrogation;directed evolution;diverse genetic building blocks;ESCHERICHIA-COLI;experimentation;expression;extensive prior knowledge;favorable parameter combinations;GENE;genetic diversity;high-throughput screening data;improved dynamic range;larger networks;library;library screening;LOGIC-CIRCUIT;long-standing challenge;MAMMALIAN-CELLS;miRNA inputs;miRNA sensor;MODEL;model validation;model-guided combinatorial optimization;model-guided generation;modeling;normal form circuits;novel proportional miRNA biosensor;phase space;predictive modeling;principle arbitrary logic;quantitative performance criteria;REGULATOR;RNA-BINDING PROTEINS;screening;search;sensor circuits;sensor genetic composition;Sensors;small number;specific genetic compositions;SPECIFICITIES;strategy;study;synthetic biology;Synthetic gene circuit;validated model
Schreiber, J
AUTOMATED DESIGN;CONSTRUCTION;directed evolution;ESCHERICHIA-COLI;EXPRESSION;library screening;LOGIC-CIRCUIT;MAMMALIAN-CELLS;miRNA sensor;modeling;REGULATOR;RNA-BINDING PROTEINS;SPECIFICITIES;Synthetic gene circuit
null
[Schreiber, Joerg; Arter, Meret; Lapique, Nicolas; Haefliger, Benjamin; Benenson, Yaakov] Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
This study is funded by Swiss National Science Foundation, NCCR "Molecular Systems Engineering" and ETH Zurich. We thank Urs Senn from the Liquid Automation Facility for the development of automated transfection protocols. We thank T. Horn, T. Lopes, and V. Jaggin for their help with flow cytometry; and N. Beerenwinkel, P. Mohammadi, and the members of Benenson laboratory for discussions.
biosensor integration;biosensor reprogramming;combination;complex gene networks;complex three-gene circuit;data;detailed mechanistic interrogation;diverse genetic building blocks;experimentation;extensive prior knowledge;favorable parameter combinations;gene;genetic diversity;high-throughput screening data;improved dynamic range;larger networks;library;long-standing challenge;miRNA inputs;model;model validation;model-guided generation;normal form circuits;novel proportional miRNA biosensor;phase space;predictive modeling;principle arbitrary logic;quantitative performance criteria;screening;search;sensor circuits;sensor genetic composition;sensors;small number;specific genetic compositions;strategy;study;synthetic biology;validated model
10.1002/bit.10713;10.1002/jgm.314;10.1016/j.celrep.2016.07.061;10.1016/j.copbio.2009.08.007;10.1016/j.jbiotec.2016.01.005;10.1016/j.stem.2015.04.005;10.1021/acssynbio.5b00040;10.1038/35002125;10.1038/35002131;10.1038/msb.2008.62;10.1038/msb.2010.2;10.1038/nbt.1536;10.1038/nbt.1568;10.1038/nbt.2149;10.1038/nbt.2714;10.1038/nbt.3300;10.1038/nbt.3301;10.1038/nbt1307;10.1038/nchembio.1680;10.1038/nchembio.1736;10.1038/ncomms10709;10.1038/ncomms11163;10.1038/ncomms5729;10.1039/c2mb25483b;10.1042/BST0370918;10.1073/pnas.1120788109;10.1073/pnas.1203831109;10.1073/pnas.1205693109;10.1073/pnas.1422023112;10.1073/pnas.252535999;10.1073/pnas.89.12.5547;10.1074/jbc.M007690200;10.1093/bioinformatics/btm362;10.1093/nar/gkg595;10.1101/gr.089367.108;10.1126/science.1170160;10.1126/science.1205527;10.1126/science.aac7341;10.1146/annurev.biophys.36.040306.132600;10.1162/ARTL_a_00160;10.1371/journal.pbio.1001528;10.1371/journal.pone.0046688;10.1529/biophysj.104.044131;[10.1038/NMETH.2404, 10.1038/nmeth.2404];[10.1038/nnano.2010.135, 10.1038/NNANO.2010.135]
Swiss Fed Inst Technol
Arter, M;Benenson, Y;Haefliger, B;Lapique, N;Schreiber, J
Schreiber, J: Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
null
null
47
null
Switzerland
Swiss Fed Inst Technol
Schreiber, Joerg
Green Published, gold
AUTOMATED DESIGN;CONSTRUCTION;DIRECTED EVOLUTION;ESCHERICHIA-COLI;EXPRESSION;LOGIC-CIRCUIT;MAMMALIAN-CELLS;REGULATOR;RNA-BINDING PROTEINS;SPECIFICITIES
Schreiber, Joerg; Arter, Meret; Lapique, Nicolas; Haefliger, Benjamin; Benenson, Yaakov;
null
Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
null
library screening;miRNA sensor;modeling;Synthetic gene circuit
12
1992;2000;2001;2002;2003;2004;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016;2017
19
Swiss Fed Inst Technol, Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
Mol. Syst. Biol.
Benenson, Yaakov
WILEY
,;a;access;and;applied;arbitrary;be;been;biology;biosensor;blocks;building;by;can;challenge;circuit;circuits;combination;combinations;complex;composition;compositions;constructing;criteria;data;detailed;diverse;diversity;dynamic;enabling;experimentation;extensive;facilitated;favorable;followed;for;form;from;further;gene;generate;generation;genetic;greatly;has;here;high-throughput;how;improved;in;including;initiate;inputs;integration;interrogation;into;knowledge;larger;library;logic;long-standing;mechanistic;miRNA;model;model-guided;modeling;networks;normal;novel;number;obtained;of;optimize;optimizing;order;parameter;performance;phase;predictive;principle;prior;proportional;quantitative;range;reprogramming;reveals;satisfy;screening;search;sensor;sensors;show;small;space;specific;strategy;study;successfully;synthetic;that;the;three-gene;to;uncover;used;using;validate;validated;validation;was;we;with;without
Swiss Fed Inst Technol
Constructing gene circuits that satisfy quantitative performance criteria has been a long-standing challenge in synthetic biology. Here, we show a strategy for optimizing a complex three-gene circuit, a novel proportional miRNA biosensor, using predictive modeling to initiate a search in the phase space of sensor genetic composition. We generate a library of sensor circuits using diverse genetic building blocks in order to access favorable parameter combinations and uncover specific genetic compositions with greatly improved dynamic range. The combination of high-throughput screening data and the data obtained from detailed mechanistic interrogation of a small number of sensors was used to validate the model. The validated model facilitated further experimentation, including biosensor reprogramming and biosensor integration into larger networks, enabling in principle arbitrary logic with miRNA inputs using normal form circuits. The study reveals how model-guided generation of genetic diversity followed by screening and model validation can be successfully applied to optimize performance of complex gene networks without extensive prior knowledge.
null
AUTOMATED DESIGN;CONSTRUCTION;DIRECTED EVOLUTION;ESCHERICHIA-COLI;EXPRESSION;LOGIC-CIRCUIT;MAMMALIAN-CELLS;REGULATORS;RNA-BINDING PROTEINS;SPECIFICITY
2
null
library screening;miRNA sensor;modeling;Synthetic gene circuit
14
ESCHERICHIA-COLI;AUTOMATED DESIGN;CONSTRUCTION;directed evolution;EXPRESSION;library screening;LOGIC-CIRCUIT;MAMMALIAN-CELLS;miRNA sensor;MODEL;REGULATOR;RNA-BINDING PROTEINS;SPECIFICITY;synthetic gene circuits
WOS:000400097600010
Swiss Fed Inst Technol, Basel, Switzerland
Switzerland
2,016
null
0000-0003-1217-8597
null
null
English
null
ACS SYNTH BIOL;ANNU REV BIOPH BIOM;ARTIF LIFE;BIOCHEM SOC T;BIOINFORMATICS;BIOPHYS J;BIOTECHNOL BIOENG;CELL REP;CELL STEM CELL;CELL SYSTEM IN PRESS;CURR OPIN BIOTECH;GENOME RES;J BIOL CHEM;J BIOTECHNOL;J GENE MED;MOL BIOSYST;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT NANOTECHNOL;NAT STRUCT BIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS BIOL;PLOS ONE;SCIENCE
Arter, Meret;Benenson, Yaakov;Haefliger, Benjamin;Lapique, Nicolas;Schreiber, Joerg
2024-03-11 ER
Alipanahi, B;Angelici, B;Batt, G;Beisel, C L;Benes, D;Carey, L B;Choi, Y;Egbert, R G;Ellefson, J W;Ellis, T;Elowitz, M B;Feng, X J;Folcher, M;Fux, C;Gardner, T S;Gossen, M;Haefliger, B;Haseltine, E L;Jeschek, M;Kudla, G;Lapique, N;Lee, I;Leisner, M;Li, Y Q;Lou, C B;Marchisio, M A;Miki, K;Mohammadi, P;Mutalik, V K;Nielsen, A A K;Orth, P;Prochazka, L;Rinaudo, K;Rodrigo, G;Salis, H M;Sayeg, M K;Schaerli, Y;Selcuklu, S D;Temme, K;Villaverde, A F;Weber, W;Wroblewska, L;Xie, Z;Yokobayashi, Y;Zhang, F Z;Zhou, T Y;Zuker, M
ET2JL
Basel, Switzerland
22
null
1
null
28,031,353
Arter, Meret;Benenson, Yaakov;Haefliger, Benjamin;Lapique, Nicolas;Schreiber, Joerg
MOL SYST BIOL
Basel, Switzerland
Song, A G;Wang, N
10.1109/TNNLS.2015.2495155
null
445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
2v67t4b3bc6f6n2r6c54135k13k3q33q28i
Enhanced Logical Stochastic Resonance in Synthetic Genetic Networks
Southeast Univ
null
Wang, N (corresponding author), Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China.
null
Song, Aiguo;Wang, Nan
Computer Science, Artificial Intelligence;Computer Science, Hardware & Architecture;Computer Science, Theory & Methods;Engineering, Electrical & Electronic
National Science Foundation of China [61272379, 61325018]
WOS
Wang, N
Southeast Univ, Jiangsu, Peoples R China
27
enhanced;genetic;in;logical;networks;resonance;stochastic;synthetic
1
null
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China
Article
Southeast Univ
PISCATAWAY
null
null
Southeast Univ
National Science Foundation of China
Wang, N (corresponding author), Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China.
2739
Song, Aiguo;Wang, Nan
37
1
388,919,600,023
National Science Foundation of China [61272379, 61325018]
China
IEEE TRANSACTIONS ON NEURAL NETWORKS AND LEARNING SYSTEMS
China
null
null
Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China
2162-237X
Song, A G;Wang, N
DEC
a.g.song@seu.edu.cn;wangnanseu@163.com
enhanced Logical Stochastic Resonance;synthetic genetic networks
2
J
Computer Science;Engineering
amplitude;background Gaussian noise;background noise;bacteriophage lambda;bistable system;brief;clear Set-Reset latch operation;concept;correct probability;decreases;desired logic operation;desired logic operation first increases;enhanced Logical Stochastic Resonance;frequency;genetic network;genetic regulatory network;increases;interplay;length;LOGICAL STOCHASTIC RESONANCE;lower;memory gates;moderate;NETWORK;noise strength;optimal plateau;output logic operation;point;required;robust Set-Reset latch operation;same time;Set-Reset latch;stability;stochastic resonance;synthetic gene network;synthetic genetic networks;unity
Wang, N
BISTABLE SYSTEM;genetic network;memory gates;STABILITY;stochastic resonance
2736
[Wang, Nan; Song, Aiguo] Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China.
This work was supported by the National Science Foundation of China under Grant 61272379 and Grant 61325018.
amplitude;background Gaussian noise;background noise;bacteriophage lambda;brief;clear Set-Reset latch operation;concept;correct probability;decreases;desired logic operation;desired logic operation first increases;frequency;genetic regulatory network;increases;interplay;length;logical stochastic resonance;lower;moderate;network;noise strength;optimal plateau;output logic operation;point;required;robust Set-Reset latch operation;same time;Set-Reset latch;synthetic gene network;unity
10.1007/s11071-013-1136-9;10.1016/j.cnsns.2013.12.008;10.1016/j.physleta.2012.01.039;10.1038/35002125;10.1038/nature01257;10.1038/nature07389;10.1038/nbt1413;10.1063/1.1345702;10.1103/PhysRevE.84.055201;10.1103/PhysRevE.88.052721;10.1103/PhysRevLett.102.104101;10.1109/TCSI.2006.883882;10.1109/TCSII.2007.901631;10.1140/epjb/e2014-50193-2;10.1186/1754-1611-4-4;10.1209/0295-5075/93/18001;10.1209/0295-5075/93/50001;10.1371/journal.pone.0076032;10.7498/aps.62.190510
Southeast Univ
Song, A G;Wang, N
Wang, N: Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China
null
61272379;61325018
19
null
China
Southeast Univ
Wang, Nan
null
BISTABLE SYSTEM;STABILITY
Wang, Nan; Song, Aiguo;
null
Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China
Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China
2162-2388
Genetic networks;memory gates;stochastic resonance
12
2000;2001;2002;2006;2007;2008;2009;2010;2011;2012;2013;2014
26
Southeast Univ, Sch Instrument Sci & Engn, Nanjing 210096, Jiangsu, Peoples R China
IEEE Trans. Neural Netw. Learn. Syst.
Song, Aiguo
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
,;a;adding;addition;also;amplitude;and;applied;as;at;background;bacteriophage;be;brief;by;can;clear;concept;correct;decreases;derived;desired;easily;first;forcing;frequency;from;Gaussian;gene;genetic;getting;implement;in;increase;increases;indicate;interplay;is;lambda;latch;length;logic;logical;lower;may;moderate;morphed;network;noise;obtained;obtaining;of;only;operation;optimal;out;output;periodic;plateau;point;probability;regulatory;required;resonance;robust;same;Set-Reset;stochastic;strength;subjected;synthetic;than;that;the;then;this;time;to;tuning;unity;using;we;what;when
Southeast Univ
In this brief, the concept of logical stochastic resonance is applied to implement the Set-Reset latch in a synthetic gene network derived from a bacteriophage lambda. Clear Set-Reset latch operation is obtained when the network is only subjected to periodic forcing. The correct probability of obtaining the desired logic operation first increases to unity and then decreases as the amplitude of the periodic forcing increases. In addition, the output logic operation can be easily morphed by tuning the frequency and the amplitude of the periodic forcing. At the same time, we indicate that adding moderate periodic forcing to the background Gaussian noise may increase the length of the optimal plateau of getting the desired logic operation in genetic regulatory network. We also point out that robust Set-Reset latch operation can be obtained using the interplay of periodic forcing and background noise when the noise strength is lower than what is required.
null
BISTABLE SYSTEM;STABILITY
2
null
genetic network;memory gates;stochastic resonance
4
BISTABLE SYSTEM;Genetic networks;memory gates;STABILITY;stochastic resonance
WOS:000388919600023
Southeast Univ, Jiangsu, Peoples R China
China
2,016
null
null
null
null
English
null
ACTA PHYS SIN-CH ED;CHAOS;COMMUN NONLINEAR SCI;EPL-EUROPHYS LETT;EUR PHYS J B;IEEE T CIRCUITS-I;IEEE T CIRCUITS-II;J Biol Eng;NAT BIOTECHNOL;NATURE;NONLINEAR DYNAM;PHYS LETT A;PHYS REV E;PHYS REV LETT;PLOS ONE
Song, Aiguo;Wang, Nan
2024-03-11 ER
Ando, H;Canton, B;Dari, A;Elowitz, M B;Gupta, A;Hasty, J;Hellen, E H;Jin, X Q;Kohar, V;Li, C G;Murali, K;Nistala Goutam, J;Sharma, A;Stricker, J;Wang, N;Xu, Y
ED5VE
Jiangsu, Peoples R China
27
null
1
null
26,571,540
Song, Aiguo;Wang, Nan
IEEE T NEUR NET LEAR
Jiangsu, Peoples R China
Gaytán, P;Roldán-Salgado, A;Sánchez-Barreto, C
10.1016/j.gene.2016.07.026
null
PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
5y106wu11264k402e3m4s5q3j494c23k1q2l50
LanFP10-A, first functional fluorescent protein whose chromophore contains the elusive mutation G67A
Univ Nacl Autonoma Mexico
null
Gaytán, P (corresponding author), Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico.
null
Gaytan, Paul;Roldan-Salgado, Abigail;Sanchez-Barreto, Celidee
Genetics & Heredity
null
WOS
Gaytán, P
Univ Nacl Autonoma Mexico, Morelos, Mexico
592
,;chromophore;contains;elusive;first;fluorescent;functional;G67A;lanFP10-A;mutation;protein;the;whose
1
null
ELSEVIER SCIENCE BV
Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
Article
Univ Nacl Autonoma Mexico
AMSTERDAM
null
null
Univ Nacl Autonoma Mexico
null
Gaytán, P (corresponding author), Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico.
290
Gaytan, Paul;Roldan-Salgado, Abigail;Sanchez-Barreto, Celidee
19
1
384,387,600,007
null
Mexico
GENE
Mexico
null
null
Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
0378-1119
Gaytán, P;Roldán-Salgado, A;Sánchez-Barreto, C
NOV 5
paul@ibt.unam.mx
chromophore;elusive mutation G67A;first functional fluorescent protein;lanFP10-A
3
J
Genetics & Heredity
1994;amino acid;Autofluorescent proteins;biosynthesis;Branchiostoma;C 2016 Elsevier B.V;chromophore;contrast;different reported chromophores;E. coli;elusive mutation G67A;entire protein family;first;first functional fluorescent protein;formation;functional yellow fluorescent protein;G67A mutation;GENE SYNTHESIS;genes encoding;Genetic reporters;genome;GFP FAMILY;GFP-like proteins;glycine 67 (Gly67);GREEN;Green Fluorescent Protein (GFP);heterologous systems;INTERMEDIATE;ISOMERIZATION;lancelet Branchiostoma floridae;lancelet genome;lanFP10-A;LanFP6-A;mutagenesis;mutants;natural autofluorescent proteins (AFPs);natural G67A mutation;natural protein;non-fluorescent;physicochemical properties;POSTTRANSLATIONAL CHEMISTRY;protein engineering;PROTEIN EXPRESSION;rights reserved;second GFP-like protein;synthetic gene encoding LanFP10-A;synthetic genes;twenty-two-year period;VARIANTS
Roldán-Salgado, A
Autofluorescent proteins;BIOSYNTHESIS;Branchiostoma;G67A mutation;GENE SYNTHESIS;Genetic reporters;GFP FAMILY;GFP-like proteins;GREEN;INTERMEDIATE;ISOMERIZATION;mutagenesis;MUTANTS;POSTTRANSLATIONAL CHEMISTRY;Protein engineering;PROTEIN EXPRESSION;Synthetic genes;VARIANTS
281
[Roldan-Salgado, Abigail; Sanchez-Barreto, Celidee; Gaytan, Paul] Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico.
null
1994;amino acid;contrast;different reported chromophores;E. coli;entire protein family;first;formation;functional yellow fluorescent protein;G67A mutation;genes encoding;genome;glycine 67 (Gly67);Green Fluorescent Protein (GFP);heterologous systems;lancelet Branchiostoma floridae;lancelet genome;LanFP10-A;LanFP6-A;natural autofluorescent proteins (AFPs);natural G67A mutation;natural protein;non-fluorescent;physicochemical properties;protein engineering;second GFP-like protein;synthetic gene encoding LanFP10-A;twenty-two-year period
10.1002/pro.654;10.1016/0014-5793(79)80818-2;10.1016/0378-1119(89)90358-2;10.1016/0378-1119(95)00685-0;10.1016/j.bbrc.2005.04.166;10.1016/j.bios.2009.06.008;10.1016/j.chembiol.2008.07.009;10.1016/j.chemphys.2008.02.055;10.1016/j.gene.2009.07.003;10.1016/j.jbiotec.2006.01.015;10.1016/j.jmb.2012.01.044;10.1016/j.mimet.2015.08.005;10.1016/S0006-3495(97)78307-3;10.1016/S0960-9822(02)00450-5;10.1016/S1367-5931(03)00097-8;10.1021/bi0479205;10.1021/cr2001965;10.1021/ja0552693;10.1021/ja056635l;10.1021/ja2114568;10.1021/ja973019j;10.1021/sb3001326;10.1038/nature06967;10.1038/nbt0295-151;10.1038/NMETH1083;10.1039/b903641p;10.1039/b904023d;10.1073/pnas.2133463100;10.1073/pnas.91.26.12501;10.1073/pnas.97.22.11990;10.1074/jbc.M412327200;10.1074/jbc.M800599200;10.1093/nar/gnh058;10.1107/S0907444913004034;10.1134/S000629790903002X;10.1186/1471-2091-3-7;10.1186/1471-2148-9-77;10.1186/1745-6150-3-28;10.1371/journal.pone.0023513;10.2144/000113765;[10.1038/NMETH.2413, 10.1038/nmeth.2413]
Univ Nacl Autonoma Mexico
Gaytán, P;Roldán-Salgado, A;Sánchez-Barreto, C
Roldán-Salgado, A: Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
null
null
42
null
Mexico
Univ Nacl Autonoma Mexico
Roldan-Salgado, Abigail
null
BIOSYNTHESIS;GENE SYNTHESIS;GFP FAMILY;GREEN;INTERMEDIATE;ISOMERIZATION;MUTAGENESIS;MUTANTS;POSTTRANSLATIONAL CHEMISTRY;VARIANTS
Roldan-Salgado, Abigail; Sanchez-Barreto, Celidee; Gaytan, Paul;
null
Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
1879-0038
Autofluorescent proteins;Branchiostoma;Protein engineering;G67A mutation;Genetic reporters;GFP-like proteins;protein expression;Synthetic gene
2
1979;1981;1989;1994;1995;1996;1997;1998;2000;2002;2003;2004;2005;2006;2007;2008;2009;2011;2012;2013;2015
8
Univ Nacl Autonoma Mexico, Inst Biotechnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico
Gene
Gaytan, Paul
ELSEVIER SCIENCE BV
(AFPs);(GFP);(Gly67);,;1994;67;a;acid;also;amino;and;as;autofluorescent;been;Branchiostoma;by;chromophores;cloned;coli;containing;contains;contrast;demonstrate;different;E.;encoded;encoding;engineering;entire;essential;expressed;family;first;floridae;fluorescent;for;formation;found;functional;G67A;gene;genes;genome;GFP-like;glycine;green;has;have;heterologous;improve;in;is;lancelet;LanFP10-A;LanFP6-A;many;modified;mutation;natural;non-fluorescent;of;only;other;period;physicochemical;produces;properties;protein;proteins;regarded;reported;second;since;subsequently;successfully;synthetic;systems;that;the;their;this;throughout;to;twenty-two-year;was;we;when;work;yellow
Univ Nacl Autonoma Mexico
Since Green Fluorescent Protein (GFP) was first successfully expressed in heterologous systems in 1994, many genes encoding other natural autofluorescent proteins (AFPs) have been cloned and subsequently modified by protein engineering to improve their physicochemical properties. Throughout this twenty-two-year period, glycine 67 (Gly67) has been regarded as the only amino acid in the entire protein family that is essential for the formation of the different reported chromophores. In this work, we demonstrate that a synthetic gene encoding LanFP10-A, a natural protein encoded in the genome of the lancelet Branchiostoma floridae containing the G67A mutation, produces a heterologous, functional yellow fluorescent protein when expressed in E. coli. In contrast to LanFP10-A, LanFP6-A, a second GFP-like protein found in the lancelet genome that also contains the natural G67A mutation, was non-fluorescent.
null
BIOSYNTHESIS;GENE SYNTHESIS;GFP FAMILY;GREEN;INTERMEDIATE;ISOMERIZATION;MUTAGENESIS;MUTANTS;POSTTRANSLATIONAL CHEMISTRY;VARIANTS
0
null
Autofluorescent proteins;Branchiostoma;G67A mutation;Genetic reporters;GFP-like proteins;Protein engineering;protein expression;Synthetic genes
10
Autofluorescent proteins;BIOSYNTHESIS;Branchiostoma;Protein engineering;G67A mutation;GENE SYNTHESIS;Genetic reporters;GFP FAMILY;GFP-like proteins;GREEN;INTERMEDIATE;ISOMERIZATION;mutagenesis;MUTANTS;POSTTRANSLATIONAL CHEMISTRY;PROTEIN EXPRESSION;Synthetic gene;VARIANTS
WOS:000384387600007
Univ Nacl Autonoma Mexico, Morelos, Mexico
Mexico
2,016
null
null
null
null
English
null
ACS SYNTH BIOL;ACTA CRYSTALLOGR D;BIO-TECHNOL;BIOCHEM BIOPH RES CO;BIOCHEMISTRY-MOSCOW+;BIOCHEMISTRY-US;BIOL DIRECT;BIOLUMINESCENCE CHEM;BIOPHYS J;BIOSENS BIOELECTRON;BIOTECHNIQUES;BMC BIOCHEM;BMC EVOL BIOL;CHEM BIOL;CHEM PHYS;CHEM REV;CHEM SOC REV;CURR BIOL;CURR OPIN CHEM BIOL;FEBS LETT;GENE;J AM CHEM SOC;J BIOL CHEM;J BIOTECHNOL;J MICROBIOL METH;J MOL BIOL;NAT METHODS;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;PROTEIN SCI
Gaytan, Paul;Roldan-Salgado, Abigail;Sanchez-Barreto, Celidee
2024-03-11 ER
Barondeau, D P;Baumann, D;Bomati, E K;Branchini, B R;Bravaya, K B;Bulina, M E;Chu, J;Cormack, B P;Craggs, T D;Delagrave, S;Gaytán, P;Gross, L A;Heim, R;Hein, R;Ho, S N;Lemay, N P;Li, G;Miyawaki, A;Pakhomov, A A;Patterson, G H;Pletnev, S;Pletneva, N V;Putnam, N H;Shaner, N C;Shcherbo, D;Shimomura, O;Sniegowski, J A;Stepanenko, O V;Subach, F V;Tejerizo, G T;Wang, Q;Ward W.W.;Wu, G;Young, L;Zimmer, M
DX4YS
Morelos, Mexico
9
null
1
null
27,418,528
Gaytan, Paul;Roldan-Salgado, Abigail;Sanchez-Barreto, Celidee
GENE
Morelos, Mexico
Lord, N D;Paulsson, J;Potvin-Trottier, L;Vinnicombe, G
10.1038/nature19841
null
MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
4f6i253w7232695a4f353n6t6x685k614fxix
Synchronous long-term oscillations in a synthetic gene circuit
Harvard Med Sch
null
Paulsson, J (corresponding author), Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA.
null
Lord, Nathan D;Paulsson, Johan;Potvin-Trottier, Laurent;Vinnicombe, Glenn
Multidisciplinary Sciences
NSF [ECS-0335765, 1517372]; Natural Sciences and Engineering Research Council of Canada (NSERC); Fonds de recherche du Quebec - Nature et technologies; National Institutes of Health (NIH) [GM081563, GM095784]; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [1517372] Funding Source: National Science Foundation
WOS
Paulsson, J
Harvard Med Sch, Boston, MA USA;Harvard Univ, Cambridge, MA USA;Univ Cambridge, Cambridge, England
538
a;circuit;gene;in;long-term;oscillations;synchronous;synthetic
2
Lord, Nathan;Potvin-Trottier, Laurent
NATURE PUBLISHING GROUP
Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA;Harvard Univ, Biophys Program, Cambridge, MA 02138 USA;Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA;Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England
Article
Harvard Med Sch
LONDON
null
null
Harvard Med Sch;Harvard Univ;Univ Cambridge
Direct For Mathematical & Physical Scien;Division Of Mathematical Sciences;Fonds de recherche du Quebec - Nature et technologies;National Institutes of Health (NIH);Natural Sciences and Engineering Research Council of Canada (NSERC);NSF
Paulsson, J (corresponding author), Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA.
+
Lord, Nathan D;Paulsson, Johan;Potvin-Trottier, Laurent;Vinnicombe, Glenn
118
4
386,654,400,059
Direct For Mathematical & Physical Scien;Division Of Mathematical Sciences [1517372] Funding Source: National Science Foundation;Fonds de recherche du Quebec - Nature et technologies;National Institutes of Health (NIH) [GM081563, GM095784];Natural Sciences and Engineering Research Council of Canada (NSERC);NSF [ECS-0335765, 1517372]
UK;USA
NATURE
USA
null
null
Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA
0028-0836
Lord, N D;Paulsson, J;Potvin-Trottier, L;Vinnicombe, G
OCT 27
johan_paulsson@harvard.edu
synchronous long-term oscillations;synthetic gene circuit
4
J
Science & Technology - Other Topics
cells;circuit design;colonies;control loops;coupling;CYANOBACTERIA;error propagation;existing features;expression;first synthetic genetic oscillator;flasks;fluctuations;Genetic circuits;growth conditions;hundreds;importance;information losses;kept phase;modification;natural systems;NETWORK;noise;noise analyses;precision;principles;range;regular;repressilator(1);results;rivals natural systems;ROBUST;robust oscillations;simplest synthetic genetic networks;single cells;stochastic chemistry;streamlined circuits kept 14 generation periods;synchronous long-term oscillations;synthetic biology;Synthetic gene circuit;wide variety
Potvin-Trottier, L
CELLS;CYANOBACTERIA;EXPRESSION;FLUCTUATIONS;NETWORK;NOISE;ROBUST
514
[Potvin-Trottier, Laurent; Lord, Nathan D.; Paulsson, Johan] Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA. [Potvin-Trottier, Laurent] Harvard Univ, Biophys Program, Cambridge, MA 02138 USA. [Lord, Nathan D.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Vinnicombe, Glenn] Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
We thank M. Elowitz for the repressilator plasmids, D. Landgraf for strains and plasmids, P. Cluzel for the fluorescent proteins, S. G. Megason and his laboratory for their microscope, R. Chait and M. Baym for the macroscope and C. Saenz for technical help on the microfluidics device. Some work was performed at the Harvard Medical School Microfluidics Facility and the Center for Nanoscale Systems, a member of the National Nanotechnology Infrastructure Network supported by NSF award ECS-0335765. L.P.-T. acknowledges fellowship support from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Fonds de recherche du Quebec - Nature et technologies. This work was supported by National Institutes of Health (NIH) grants (GM081563 and GM095784) and NSF award 1517372.
cells;circuit design;colonies;control loops;coupling;error propagation;existing features;first synthetic genetic oscillator;flasks;genetic circuits;growth conditions;hundreds;importance;information losses;kept phase;modification;natural systems;noise analyses;precision;principles;range;regular;repressilator(1);results;rivals natural systems;robust oscillations;simplest synthetic genetic networks;single cells;stochastic chemistry;streamlined circuits kept 14 generation periods;synthetic biology;wide variety
10.1002/0471142727.mb1420s92;10.1016/j.cell.2009.04.048;10.1016/j.cell.2014.02.022;10.1016/j.cub.2010.04.045;10.1016/S0006-3495(00)76377-6;10.1017/S0033583501003663;10.1038/35002125;10.1038/nature02533;10.1038/nature03508;10.1038/nature06395;10.1038/nature07389;10.1038/nature07616;10.1038/nature08753;10.1038/nature09333;10.1038/nature12148;10.1038/nature12804;10.1038/nature13238;10.1073/pnas.092133899;10.1073/pnas.110057697;10.1103/PhysRevLett.94.218102;10.1126/science.1108451;10.1126/science.1172005;10.1126/science.1205369;10.1126/science.1230996;10.1126/science.1232758;10.1126/science.271.5251.990;10.1186/1752-0509-8-S4-S4;10.1371/journal.pone.0015179;10.2307/2006360, 10.2307/2006360];10.7554/eLife.09771
Harvard Med Sch
Lord, N D;Paulsson, J;Potvin-Trottier, L;Vinnicombe, G
Potvin-Trottier, L: Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA
Potvin-Trottier, Laurent
1517372;ECS-0335765;GM081563;GM095784
36
null
USA
Harvard Med Sch;Harvard Univ;Univ Cambridge
Potvin-Trottier, Laurent
Green Submitted, Green Accepted
CELLS;CYANOBACTERIA;EXPRESSION;FLUCTUATIONS;NETWORK;NOISE;ROBUST
Potvin-Trottier, Laurent; Lord, Nathan D.; Vinnicombe, Glenn; Paulsson, Johan;
null
Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA;Harvard Univ, Biophys Program, Cambridge, MA 02138 USA;Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA;Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England
Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA;Harvard Univ, Biophys Program, Cambridge, MA 02138 USA;Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA;Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England
1476-4687
null
7626
1926;1958;1968;1978;1996;1998;1999;2000;2001;2002;2004;2005;2007;2008;2009;2010;2011;2013;2014;2015
182
Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA
Nature
Paulsson, Johan
NATURE PUBLISHING GROUP
,;14;a;accurate;achieve;adding;allowing;analyses;and;any;are;between;biology;but;by;can;cells;chemistry;circuit;circuits;colonies;conditions;control;coupling;created;design;emphasize;engineered;error;even;existing;features;first;flasks;for;from;furthermore;generally;generation;generations;genetic;growth;here;highly;hundreds;importance;in;information;it;kept;less;loops;losses;modification;modify;natural;networks;noise;not;of;oscillate;oscillations;oscillator;our;over;perform;periods;phase;precision;principles;propagation;range;reduce;regular;removing;repressilator(1);results;revisit;rivals;robust;show;simplest;simply;single;some;sought;specifically;stochastic;streamlined;suggest;synchronously;synthetic;synthetically;systems;tasks;than;that;the;them;this;to;using;variety;we;wide;without
Harvard Med Sch
Synthetically engineered genetic circuits can perform a wide variety of tasks but are generally less accurate than natural systems. Here we revisit the first synthetic genetic oscillator, the repressilator(1), and modify it using principles from stochastic chemistry in single cells. Specifically, we sought to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. We show that this modification created highly regular and robust oscillations. Furthermore, some streamlined circuits kept 14 generation periods over a range of growth conditions and kept phase for hundreds of generations in single cells, allowing cells in flasks and colonies to oscillate synchronously without any coupling between them. Our results suggest that even the simplest synthetic genetic networks can achieve a precision that rivals natural systems, and emphasize the importance of noise analyses for circuit design in synthetic biology.
AAL-3122-2021
CELLS;CYANOBACTERIA;EXPRESSION;FLUCTUATIONS;NETWORKS;NOISE;ROBUST
3
null
null
16
CELLS;CYANOBACTERIA;EXPRESSION;FLUCTUATIONS;NETWORKS;NOISE;ROBUST
WOS:000386654400059
Harvard Med Sch, Boston, MA USA;Harvard Univ, Cambridge, MA USA;Univ Cambridge, Cambridge, England
UK;USA
2,016
null
0000-0001-7876-2820;0000-0001-9553-2779
null
null
English
null
APPL ENVIRON MICROB;BIOPHYS J;BMC SYST BIOL;CELL;CURR BIOL;Curr Protoc Mol Biol;Discrete-Time Signal Processing;ELIFE;INT TECHN COMM DAY H;MEASUREMENT POWER SP;NATURE;P NATL ACAD SCI USA;PHILOS MAG;PHYS REV LETT;PLOS ONE;Q REV BIOPHYS;SCIENCE;Spectral Analysis and its Applications
Lord, Nathan D;Paulsson, Johan;Potvin-Trottier, Laurent;Vinnicombe, Glenn
2024-03-11 ER
Andersen, J B;Bell Jb.;Berg, O G;Blackman R. B.;Bonnet, J;Brewster, R C;Chabot, J R;Chait, R;Daniel, R;Danino, T;Edelstein Arthur;Elowitz, M B;Friedland, A E;Fung, E;Jenkins G. M.;Keiler, K C;Lestas, I;Mckane, A J;Mihalcescu, I;Mondragón-Palomino, O;Moriya, T;Nakajima, M;Niederholtmeyer, H;Norman, T M;Oppenheim A., V;Paulsson, J;Prindle, A;Stricker, J;Tabor, J J;Teng, S W;Tigges, M;Van Der Pol, B;Verdu S.;Vilar, J M G;Wang, P
EA5IY
Boston, MA USA
233
null
3
null
27,732,583
Lord, Nathan D;Paulsson, Johan;Potvin-Trottier, Laurent;Vinnicombe, Glenn
NATURE
Boston, MA USA;Cambridge, England;Cambridge, MA USA
Brady, S F;Charlop-Powers, Z;Kang, H S
10.1021/acssynbio.6b00080
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
28215455v6c4m4h4m315wc6c425w3051l2z1n
Multiplexed CRISPR/Cas9-and TAR-Mediated Promoter Engineering of Natural Product Biosynthetic Gene Clusters in Yeast
Rockefeller Univ
null
Brady, SF (corresponding author), Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA.
null
Brady, Sean F;Charlop-Powers, Zachary;Kang, Hahk-Soo
Biochemical Research Methods
NIH [U01 GM110714-1A1, AI110029]
WOS
Brady, S F
Konkuk Univ, Seoul, South Korea;Rockefeller Univ, New York, NY USA
5
biosynthetic;Clusters;CRISPR/Cas9-and;engineering;gene;in;multiplexed;natural;of;Product;Promoter;TAR-Mediated;yeast
2
Charlop-Powers, Zachary
AMER CHEMICAL SOC
Konkuk Univ, Dept Bioind Technol, Seoul 143701, South Korea;Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA
Article
Rockefeller Univ
WASHINGTON
null
null
Konkuk Univ;Rockefeller Univ
NIH
Brady, SF (corresponding author), Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA.
1010
Brady, Sean F;Charlop-Powers, Zachary;Kang, Hahk-Soo
111
2
383,641,400,012
NIH [U01 GM110714-1A1, AI110029]
South Korea;USA
ACS SYNTHETIC BIOLOGY
USA
null
null
Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA
2161-5063
Brady, S F;Charlop-Powers, Z;Kang, H S
SEP
sbrady@rockefeller.edu
multiplexed CRISPR/Cas9-and TAR-Mediated Promoter Engineering;Natural Product Biosynthetic Gene Clusters;Yeast
3
J
Biochemistry & Molecular Biology
activation;approach;bacterial genomes;biosynthetic gene;biosynthetic gene clusters;combines CRISPR/Cas9;CRISPR array;CRISPR plasmid;CRISPR-CAS SYSTEMS;CRISPR/Cas9;CRISPR/Cas9 system;discovery;DISRUPTION;DNA;DNA double-strand breaks;drug discovery;first application;gene clusters;generic method;growing collection;improved yeast-based promoter engineering platform (mCRISTAR);inefficiency;laboratory growth conditions;large gene clusters;major obstacle;mCRISTAR;metagenome;method;microbial genome;multiplex CRISPR;multiplex gene cluster refactoring;multiplexed CRISPR/Cas9-and TAR-Mediated Promoter Engineering;multiplexed promoter engineering;multiplexed replacement;Natural Product Biosynthetic Gene Clusters;natural product discovery;natural products;new paradigm;OLIGONUCLEOTIDES;projects;promoter engineering;promoter regions;promoters;resulting operon fragments;revealing chemistries;SACCHAROMYCES-CEREVISIAE;simple;single auxotrophic selection;single-marker multiplexed promoter engineering;synthetic gene cluster-specific promoter cassettes;TAR;transcriptional silence;use;yeast
Kang, H S
ACTIVATION;CRISPR-CAS SYSTEMS;CRISPR/Cas9;DISRUPTION;DRUG DISCOVERY;natural products;OLIGONUCLEOTIDES;promoter engineering;SACCHAROMYCES-CEREVISIAE;TAR
1002
[Kang, Hahk-Soo; Charlop-Powers, Zachary; Brady, Sean F.] Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA. [Kang, Hahk-Soo] Konkuk Univ, Dept Bioind Technol, Seoul 143701, South Korea.
This work was supported by NIH (U01 GM110714-1A1 and AI110029 to Z.C.-P.).
approach;bacterial genomes;biosynthetic gene;biosynthetic gene clusters;combines CRISPR/Cas9;CRISPR array;CRISPR plasmid;CRISPR/Cas9;CRISPR/Cas9 system;discovery;DNA;DNA double-strand breaks;first application;gene clusters;generic method;growing collection;improved yeast-based promoter engineering platform (mCRISTAR);inefficiency;laboratory growth conditions;large gene clusters;major obstacle;mCRISTAR;metagenome;method;microbial genome;multiplex CRISPR;multiplex gene cluster refactoring;multiplexed promoter engineering;multiplexed replacement;natural product biosynthetic gene clusters;natural product discovery;natural products;new paradigm;projects;promoter regions;promoters;resulting operon fragments;revealing chemistries;simple;single auxotrophic selection;single-marker multiplexed promoter engineering;synthetic gene cluster-specific promoter cassettes;TAR;transcriptional silence;use
10.1002/bip.21450;10.1007/s00253-010-3018-0;10.1016/j.cell.2014.06.034;10.1016/j.ymben.2015.01.008;10.1016/S0076-6879(05)09019-1;10.1021/ja3093828;10.1021/sb400058n;10.1021/sb500255k;10.1038/522270a;10.1038/ja.2008.16;10.1038/nbt.2508;10.1038/nbt.2842;10.1038/ncomms3894;10.1038/nprot.2007.13;10.1038/nrd4510;10.1038/nrmicro3496;10.1042/BST20130164;10.1073/pnas.1507606112;10.1073/pnas.2036296100;10.1074/jbc.M413801200;10.1093/bioinformatics/btp163;10.1093/nar/gkt135;10.1126/science.1232033;10.1371/journal.pone.0005553
Rockefeller Univ
Brady, S F;Charlop-Powers, Z;Kang, H S
Kang, H S: Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA
null
AI110029;U01 GM110714-1A1
25
null
USA
Konkuk Univ;Rockefeller Univ
Kang, Hahk-Soo
Green Accepted
ACTIVATION;CRISPR-CAS SYSTEMS;DISRUPTION;DRUG DISCOVERY;OLIGONUCLEOTIDES;SACCHAROMYCES-CEREVISIAE
Kang, Hahk-Soo; Charlop-Powers, Zachary; Brady, Sean F.;
null
Konkuk Univ, Dept Bioind Technol, Seoul 143701, South Korea;Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA
Konkuk Univ, Dept Bioind Technol, Seoul 143701, South Korea;Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA
null
CRISPR/Cas9;promoter engineering;natural products;TAR
9
1998;2003;2005;2006;2007;2009;2010;2011;2012;2013;2014;2015
71
Rockefeller Univ, Lab Genetically Encoded Small Mol, 1230 York Ave, New York, NY 10065 USA
ACS Synth. Biol.
Brady, Sean F
AMER CHEMICAL SOC
(mCRISTAR);,;a;an;and;application;approach;are;array;as;auxotrophic;bacterial;biosynthetic;breaks;by;cassettes;chemistries;cluster;cluster-specific;clusters;collection;combines;conditions;construction;CRISPR;CRISPR/Cas9;describe;discovery;DNA;double-strand;emerged;enable;encoded;engineering;facilitate;first;for;found;fragments;from;gene;generic;genome;genomes;growing;growth;guide;has;here;highlights;implementing;improve;improved;in;induce;inefficiency;is;laboratory;large;major;mCRISTAR;metagenome;method;microbial;multiplex;multiplexed;natural;new;obstacle;of;operon;paradigm;plasmid;platform;product;products;projects;promoter;promoters;rapidly;reassembled;refactoring;regions;replacement;resulting;revealing;selection;sequencing;silence;simple;simplify;single;single-marker;synthetic;system;TAR;that;the;this;to;transcriptional;under;use;used;uses;using;we;will;yeast-based
Rockefeller Univ
The use of DNA sequencing to guide the discovery of natural products has emerged as a new paradigm for revealing chemistries encoded in bacterial genomes. A major obstacle to implementing this approach to natural product discovery is the transcriptional silence of biosynthetic gene clusters under laboratory growth conditions. Here we describe an improved yeast-based promoter engineering platform (mCRISTAR) that combines CRISPR/Cas9 and TAR to enable single-marker multiplexed promoter engineering of large gene clusters. mCRISTAR highlights the first application of the CRISPR/Cas9 system to multiplexed promoter engineering of natural product biosynthetic gene clusters. In this method, CRISPR/Cas9 is used to induce DNA double-strand breaks in promoter regions of biosynthetic gene clusters, and the resulting operon fragments are reassembled by TAR using synthetic gene cluster-specific promoter cassettes. mCRISTAR uses a CRISPR array to simplify the construction of a CRISPR plasmid for multiplex CRISPR and a single auxotrophic selection to improve the inefficiency of using a CRISPR array for multiplex gene cluster refactoring. mCRISTAR is a simple and generic method for multiplexed replacement of promoters in biosynthetic gene clusters that will facilitate the discovery of natural products from the rapidly growing collection of gene clusters found in microbial genome and metagenome sequencing projects.
null
ACTIVATION;CRISPR-CAS SYSTEMS;DISRUPTION;DRUG DISCOVERY;OLIGONUCLEOTIDES;SACCHAROMYCES-CEREVISIAE
4
null
CRISPR/Cas9;natural products;promoter engineering;TAR
9
SACCHAROMYCES-CEREVISIAE;ACTIVATION;CRISPR-Cas9;CRISPR-CAS SYSTEMS;DISRUPTION;DRUG DISCOVERY;promoter engineering;NATURAL-PRODUCTS;OLIGONUCLEOTIDES;TAR
WOS:000383641400012
Konkuk Univ, Seoul, South Korea;Rockefeller Univ, New York, NY USA
South Korea;USA
2,016
null
0000-0001-8816-4680
null
null
English
null
ACS SYNTH BIOL;APPL MICROBIOL BIOT;BIOCHEM SOC T;BIOINFORMATICS;BIOPOLYMERS;CELL;J AM CHEM SOC;J ANTIBIOT;J BIOL CHEM;METAB ENG;METHOD ENZYMOL;NAT BIOTECHNOL;NAT COMMUN;NAT PROTOC;NAT REV DRUG DISCOV;NAT REV MICROBIOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;SCIENCE;YEAST
Brady, Sean F;Charlop-Powers, Zachary;Kang, Hahk-Soo
2024-03-11 ER
Bao, Z H;Brachmann, C B;Cimermancic, P;Cock, P J A;Demain, A L;Dicarlo, J E;Engler, C;Gietz, R D;Harvey, A L;Hong, H J;Jakounas, T;Jiang, W Y;Kallifidas, D;Karvelis, T;Kim, J H;Lok, C;Luo, Y Z;Mali, P;Montiel, D;Rutledge, P J;Sander, J D;Seghezzi, N;Shao, Z Y;Storici, F
DW4VP
New York, NY USA
89
null
2
null
27,197,732
Brady, Sean F;Charlop-Powers, Zachary;Kang, Hahk-Soo
ACS SYNTH BIOL
New York, NY USA;Seoul, South Korea
Fontes, C M G A;Guerreiro, C I P D;Sequeira, A F;Vincentelli, R
10.1007/s12033-016-9957-7
null
999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
142m4z175226c5d1q3xnr003n1r4922693s
T7 Endonuclease I Mediates Error Correction in Artificial Gene Synthesis
Univ Lisbon
null
Fontes, CMGA (corresponding author), NZYTech Genes & Enzymes, Campus Lumiar,Estr Paco do Lumiar, P-1649038 Lisbon, Portugal.;Fontes, CMGA (corresponding author), Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal.
null
Fontes, Carlos M G A;Guerreiro, Catarina I P D;Sequeira, Ana Filipa;Vincentelli, Renaud
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
Fundacao para a Ciencia e a Tecnologia (Lisbon, Portugal); NZYTech [SFRH/BD/51602/2011]
WOS
Fontes, CMGA
Aix Marseille Univ, Marseille, France;NZYTech Genes & Enzymes, Lisbon, Portugal;Univ Lisbon, Lisbon, Portugal
58
Artificial;Correction;Endonuclease;Error;gene;I;in;Mediates;synthesis;t7
2
Fontes, Carlos;Sequeira, Ana Filipa
HUMANA PRESS INC
Aix Marseille Univ, CNRS, AFMB, UMR 7257, Campus Luminy,163 Ave Luminy, F-13288 Marseille 09, France;NZYTech Genes & Enzymes, Campus Lumiar,Estr Paco do Lumiar, P-1649038 Lisbon, Portugal;Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal;Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal.; Fontes, CMGA (corresponding author), NZYTech Genes & Enzymes, Campus Lumiar,Estr Paco do Lumiar, P-1649038 Lisbon, Portugal
Article
NZYTech Genes & Enzymes;Univ Lisbon
TOTOWA
null
null
Aix Marseille Univ;Ave Univ Tecn;NZYTech Genes & Enzymes;Univ Lisbon
Fundacao para a Ciencia e a Tecnologia (Lisbon, Portugal);NZYTech
Fontes, CMGA (corresponding author), Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal.; Fontes, CMGA (corresponding author), NZYTech Genes & Enzymes, Campus Lumiar,Estr Paco do Lumiar, P-1649038 Lisbon, Portugal.
584
Fontes, Carlos M G A;Guerreiro, Catarina I P D;Sequeira, Ana Filipa;Vincentelli, Renaud
23
3
382,003,200,007
Fundacao para a Ciencia e a Tecnologia (Lisbon, Portugal);NZYTech [SFRH/BD/51602/2011]
France;Portugal
MOLECULAR BIOTECHNOLOGY
Portugal
null
null
Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal
1073-6085
Fontes, C M G A;Guerreiro, C I P D;Sequeira, A F;Vincentelli, R
SEP
cafontes@fmv.ulisboa.pt
Artificial Gene Synthesis;Error Correction;t7 Endonuclease
4
J
Biochemistry & Molecular Biology;Biotechnology & Applied Microbiology
0.43 errors per 1 kb;ability;accurate production;Artificial Gene Synthesis;cleavage step (EMC);current gene synthesis protocols;data;de novo gene synthesis;deletions;different endonuclease enzymes;DNA;DNA strands;efficacy;eightfold relative;EMC;Enzyme mismatch cleavage (EMC);enzymes;Error Correction;error correction step;error frequency;error rate;Error removal;error-free synthetic genes;fidelity;gene assembly;GENE SYNTHESIS;gfp gene;green fluorescent protein;incorporation;incorrect impairments;insertions;integrated protocol;large scales;method;MISMATCH CLEAVAGE;mutation frequency;mutation removal;mutation-removal step;MUTATIONS;number;overall;overlapping oligonucleotides;PCR assembly;population;quality;removal;RESOLVASES;resulting artificial genes;sequence analysis;STRAND-SPECIFIC NUCLEASES;substitutions;synthetic genes;t7 Endonuclease;T7 endonuclease I;taken;template
Sequeira, A F
Enzyme mismatch cleavage (EMC);ENZYMES;Error removal;GENE SYNTHESIS;MISMATCH CLEAVAGE;REMOVAL;RESOLVASES;STRAND-SPECIFIC NUCLEASES;T7 endonuclease I
573
[Sequeira, Ana Filipa; Fontes, Carlos M. G. A.] Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal. [Sequeira, Ana Filipa; Guerreiro, Catarina I. P. D.; Fontes, Carlos M. G. A.] NZYTech Genes & Enzymes, Campus Lumiar,Estr Paco do Lumiar, P-1649038 Lisbon, Portugal. [Vincentelli, Renaud] Aix Marseille Univ, CNRS, AFMB, UMR 7257, Campus Luminy,163 Ave Luminy, F-13288 Marseille 09, France.
Ana Filipa Sequeira was supported by Fundacao para a Ciencia e a Tecnologia (Lisbon, Portugal) and NZYTech through the individual fellowship SFRH/BD/51602/2011.
0.43 errors per 1 kb;ability;accurate production;artificial gene synthesis;cleavage step (EMC);current gene synthesis protocols;data;de novo gene synthesis;deletions;different endonuclease enzymes;DNA;DNA strands;efficacy;eightfold relative;EMC;error correction step;error frequency;error rate;error-free synthetic genes;fidelity;gene assembly;gene synthesis;gfp gene;green fluorescent protein;incorporation;incorrect impairments;insertions;integrated protocol;large scales;method;mutation frequency;mutation removal;mutation-removal step;mutations;number;overall;overlapping oligonucleotides;PCR assembly;population;quality;resulting artificial genes;sequence analysis;substitutions;synthetic genes;T7 endonuclease;taken;template
10.1002/elps.200700729;10.1002/elps.201100460;10.1006/jmbi.1997.1097;10.1007/s00253-012-4507-0;10.1016/j.jbiotec.2006.01.015;10.1016/j.tibtech.2011.10.002;10.1016/S0168-6445(02)00129-8;10.1021/bi992376z;10.1038/srep11302;10.1039/b822268c;10.1073/pnas.94.13.6847;10.1093/nar/28.18.3417;10.1093/nar/gkh599;10.1093/nar/gkr887;10.1093/nar/gku405;10.1093/nar/gnh160;10.1093/nar/gni058;10.1093/protein/gzu029;10.1101/SQB.1984.049.01.081;10.1111/1567-1364.12171;10.1385/MB:23:1:73;10.3389/fmicb.2014.00172;[10.1038/NMETH.2918, 10.1038/nmeth.2918]
Univ Lisbon
Fontes, C M G A;Guerreiro, C I P D;Sequeira, A F;Vincentelli, R
Sequeira, A F: Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal
null
SFRH/BD/51602/2011
23
null
Portugal
Aix Marseille Univ;NZYTech Genes & Enzymes;Univ Lisbon
Sequeira, Ana Filipa
null
ENZYMES;MISMATCH CLEAVAGE;REMOVAL;RESOLVASES;STRAND-SPECIFIC NUCLEASES
Sequeira, Ana Filipa; Guerreiro, Catarina I. P. D.; Vincentelli, Renaud; Fontes, Carlos M. G. A.;
null
Aix Marseille Univ, CNRS, AFMB, UMR 7257, Campus Luminy,163 Ave Luminy, F-13288 Marseille 09, France;NZYTech Genes & Enzymes, Campus Lumiar,Estr Paco do Lumiar, P-1649038 Lisbon, Portugal;Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal
Aix Marseille Univ, CNRS, AFMB, UMR 7257, Campus Luminy,163 Ave Luminy, F-13288 Marseille 09, France;NZYTech Genes & Enzymes, Campus Lumiar,Estr Paco do Lumiar, P-1649038 Lisbon, Portugal;Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal
1559-0305
Enzyme mismatch cleavage (EMC);Error removal;Gene synthesis;T7 endonuclease I
8-9
1984;1997;2000;2003;2004;2005;2006;2008;2009;2012;2014;2015
7
NZYTech Genes & Enzymes, Campus Lumiar,Estr Paco do Lumiar, P-1649038 Lisbon, Portugal;Univ Lisbon, Fac Med Vet, CIISA, Ave Univ Tecn, P-1300477 Lisbon, Portugal
Mol. Biotechnol.
Fontes, Carlos M G A
HUMANA PRESS INC
(EMC);,;0.43;1;a;ability;accumulated;accurate;an;analysed;analysis;and;artificial;artificially;as;assembly;associated;between;both;by;can;cleavage;cleave;correction;current;data;de;deletions;depends;different;diminished;DNA;effectively;efficacy;efficient;eightfold;EMC;encodes;endonuclease;enzymatic;enzymes;error;error-free;errors;fidelity;fluorescent;following;for;frequency;from;functional;gene;genes;gfp;green;here;I;impairments;improve;improved;in;including;incorporating;incorporation;incorrect;insertions;integrated;kb;large;largely;limits;method;mismatch;mismatches;mutation;mutation-removal;mutations;not;novo;number;of;oligonucleotides;on;overall;overlapping;PCR;per;population;presented;production;protein;protocol;protocols;quality;rate;recognize;reduced;relative;removal;remove;resulting;reveal;revealed;scales;sequence;small;specifically;step;strands;strongly;substitutions;synthesis;synthesized;synthetic;T7;taken;template;that;the;this;to;together;used;using;was;we;when;which;with
NZYTech Genes & Enzymes;Univ Lisbon
Efficacy of de novo gene synthesis largely depends on the quality of overlapping oligonucleotides used as template for PCR assembly. The error rate associated with current gene synthesis protocols limits the efficient and accurate production of synthetic genes, both in the small and large scales. Here, we analysed the ability of different endonuclease enzymes, which specifically recognize and cleave DNA mismatches resulting from incorrect impairments between DNA strands, to remove mutations accumulated in synthetic genes. The gfp gene, which encodes the green fluorescent protein, was artificially synthesized using an integrated protocol including an enzymatic mismatch cleavage step (EMC) following gene assembly. Functional and sequence analysis of resulting artificial genes revealed that number of deletions, insertions and substitutions was strongly reduced when T7 endonuclease I was used for mutation removal. This method diminished mutation frequency by eightfold relative to gene synthesis not incorporating an error correction step. Overall, EMC using T7 endonuclease I improved the population of error-free synthetic genes, resulting in an error frequency of 0.43 errors per 1 kb. Taken together, data presented here reveal that incorporation of a mutation-removal step including T7 endonuclease I can effectively improve the fidelity of artificial gene synthesis.
null
ENZYMES;MISMATCH CLEAVAGE;REMOVAL;RESOLVASE;STRAND-SPECIFIC NUCLEASES
1
null
Enzyme mismatch cleavage (EMC);Error removal;Gene synthesis;T7 endonuclease I
12
ENZYMES;Enzyme mismatch cleavage (EMC);Error removal;GENE SYNTHESIS;MISMATCH CLEAVAGE;REMOVAL;RESOLVASE;STRAND-SPECIFIC NUCLEASES;T7 endonuclease I
WOS:000382003200007
Aix Marseille Univ, Marseille, France;NZYTech Genes & Enzymes, Lisbon, Portugal;Univ Lisbon, Lisbon, Portugal
France;Portugal
2,016
null
0000-0001-8445-6221;0000-0002-1219-9753
null
null
English
null
APPL MICROBIOL BIOT;BIOCHEMISTRY-US;COLD SPRING HARB SYM;ELECTROPHORESIS;FEMS MICROBIOL REV;FEMS YEAST RES;FRONT MICROBIOL;J BIOTECHNOL;J MOL BIOL;MOL BIOSYST;MOL BIOTECHNOL;NAT METHODS;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PROTEIN ENG DES SEL;SCI REP-UK;TRENDS BIOTECHNOL
Fontes, Carlos M G A;Guerreiro, Catarina I P D;Sequeira, Ana Filipa;Vincentelli, Renaud
2024-03-11 ER
Aravind, L;Babon, J J;Carr, P A;Chao, R;Cheung, R C F;Currin, A;Demassy, B;Desai, N A;Fuhrmann, M;Huang, M C;Kosuri, S;Ma, S Y;Rosano, G L;Saaem, I;Smith, J;Tian, J D;Till, B J;Tsuji, T;Wan, W;White, M F;Wu, G;Yang, B;Zampini, M
DU1XG
Lisbon, Portugal;Lisbon, Portugal.
11
null
3
null
27,334,914
Fontes, Carlos M G A;Guerreiro, Catarina I P D;Sequeira, Ana Filipa;Vincentelli, Renaud
MOL BIOTECHNOL
Lisbon, Portugal;Marseille, France
Bar-Ziv, R H;Morel, M;Nissim, L;Rotter, V;Shtrahman, R
10.1073/pnas.1604391113
null
2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
1l1013p6d3k4g2c4r3g6r1x631m2k664r185r6d
Cellular heterogeneity mediates inherent sensitivity-specificity tradeoff in cancer targeting by synthetic circuits
Weizmann Inst Sci
null
Bar-Ziv, RH (corresponding author), Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel.;Nissim, L (corresponding author), MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
null
Bar-Ziv, Roy H;Morel, Mathieu;Nissim, Lior;Rotter, Varda;Shtrahman, Roman
Multidisciplinary Sciences
null
WOS
Bar-Ziv, R H;Nissim, L
MIT, Cambridge, MA USA;Univ Paris, Paris, France;Weizmann Inst Sci, Rehovot, Israel
113
by;cancer;Cellular;circuits;heterogeneity;in;inherent;Mediates;sensitivity-specificity;synthetic;targeting;tradeoff
3
Morel, Mathieu;Nissim, Lior
NATL ACAD SCIENCES
MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Univ Paris 06, CNRS, Dept Chim,UMR PASTEUR 8640, Ecole Normale Super,Paris Sci & Lettres PSL Res U, F-75005 Paris, France;Univ Paris 06, CNRS, UMR PASTEUR 8640, Ecole Normale Super, F-75005 Paris, France;Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel;Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel.; Nissim, L (corresponding author), MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
Article
MIT;Weizmann Inst Sci
WASHINGTON
null
null
MIT;Synthet Biol Ctr;Univ Paris 06;Weizmann Inst Sci
null
Bar-Ziv, RH (corresponding author), Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel.; Nissim, L (corresponding author), MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
8138
Bar-Ziv, Roy H;Morel, Mathieu;Nissim, Lior;Rotter, Varda;Shtrahman, Roman
21
5
380,224,500,053
null
France;Israel;USA
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Israel;USA
null
null
Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel
0027-8424
Bar-Ziv, R H;Morel, M;Nissim, L;Rotter, V;Shtrahman, R
JUL 19
liorni@mit.edu;roy.bar-ziv@weizmann.ac.il
cancer;cellular heterogeneity;inherent sensitivity-specificity tradeoff;synthetic circuits
5
J
Science & Technology - Other Topics
activation threshold;analysis;background;BIOLOGY;CANCER;cancer cells;cancer gene therapy;cell-state targeting;cellular heterogeneity;cellular variability;CIRCUITS;combinatorial integration;computation;decision-making circuits;detrimental;enhanced specificity;error rates;escape;few cells;FRAMEWORK;gate acting;gate amplification gain;gene expression;GENERATION;heterogeneous cell populations;heterogeneous environment;inherent sensitivity-specificity tradeoff;inherent tradeoff;killing assay;light;mammalian synthetic biology;MAMMALIAN-CELLS;minimal loss;molecular parameters;multiple expression markers;normal ones;sensitivity;single-cell response function;specificity;synthetic circuits;synthetic circuits control specificity;synthetic gene circuits;SYSTEM;T-CELLS;target malignant state;tumor-mimicking cell-culture model;tunable logic;two promoters;unexplored;versatile means
Morel, M
BIOLOGY;cancer gene therapy;cell-state targeting;cellular heterogeneity;COMPUTATION;FRAMEWORK;GENERATION;mammalian synthetic biology;MAMMALIAN-CELLS;synthetic gene circuits;SYSTEM;T-CELLS
8133
[Morel, Mathieu; Shtrahman, Roman; Bar-Ziv, Roy H.] Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel. [Morel, Mathieu] Univ Paris 06, CNRS, Dept Chim,UMR PASTEUR 8640, Ecole Normale Super,Paris Sci & Lettres PSL Res U, F-75005 Paris, France. [Morel, Mathieu] Univ Paris 06, CNRS, UMR PASTEUR 8640, Ecole Normale Super, F-75005 Paris, France. [Rotter, Varda] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. [Nissim, Lior] MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
null
activation threshold;analysis;background;cancer;cancer cells;cellular variability;circuits;combinatorial integration;decision-making circuits;detrimental;enhanced specificity;error rates;escape;few cells;gate acting;gate amplification gain;gene expression;heterogeneous cell populations;heterogeneous environment;inherent tradeoff;killing assay;light;minimal loss;molecular parameters;multiple expression markers;normal ones;sensitivity;single-cell response function;specificity;synthetic circuits;synthetic circuits control specificity;synthetic gene circuits;target malignant state;tumor-mimicking cell-culture model;tunable logic;two promoters;unexplored;versatile means
10.1002/bit.10655;10.1002/jmr.749;10.1007/s10875-012-9689-9;10.1007/s12079-011-0132-4;10.1016/j.cell.2012.05.045;10.1016/j.cell.2015.04.042;10.1016/j.cell.2016.01.011;10.1016/j.it.2015.06.004;10.1021/sb4000564;10.1038/msb.2010.99;10.1038/msb.2013.48;10.1038/msb4100173;10.1038/nature06915;10.1038/nature09326;10.1038/nature09565;10.1038/nature11149;10.1038/nature12148;10.1038/nature12624;10.1038/nbt.2287;10.1038/nbt.2459;10.1038/nbt.2877;10.1038/nrg3094;10.1038/nrm3738;10.1042/BJ20071193;10.1088/1478-3975/4/3/002;10.1093/nar/gks142;10.1126/science.1205527;10.1126/science.1232758;10.1126/scitranslmed.3009367;10.1128/JVI.72.11.8463-8471.1998;10.1148/radiology.143.1.7063747;10.1155/S1110724303209074;10.1158/0008-5472.CAN-04-3880;10.1158/0008-5472.CAN-09-2661;[10.1038/nchembio.1433, 10.1038/NCHEMBIO.1433];[10.1038/NMAT4497, 10.1038/nmat4497]
Weizmann Inst Sci
Bar-Ziv, R H;Morel, M;Nissim, L;Rotter, V;Shtrahman, R
Morel, M: Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel
Morel, Mathieu
null
38
null
Israel
MIT;Univ Paris 06;Weizmann Inst Sci
Morel, Mathieu
Green Published, Bronze
BIOLOGY;COMPUTATION;FRAMEWORK;GENERATION;MAMMALIAN-CELLS;SYSTEM;T-CELLS
Morel, Mathieu; Shtrahman, Roman; Rotter, Varda; Nissim, Lior; Bar-Ziv, Roy H.;
null
MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Univ Paris 06, CNRS, Dept Chim,UMR PASTEUR 8640, Ecole Normale Super,Paris Sci & Lettres PSL Res U, F-75005 Paris, France;Univ Paris 06, CNRS, UMR PASTEUR 8640, Ecole Normale Super, F-75005 Paris, France;Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel;Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Univ Paris 06, CNRS, Dept Chim,UMR PASTEUR 8640, Ecole Normale Super,Paris Sci & Lettres PSL Res U, F-75005 Paris, France;Univ Paris 06, CNRS, UMR PASTEUR 8640, Ecole Normale Super, F-75005 Paris, France;Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel;Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
null
cancer gene therapy;cell-state targeting;cellular heterogeneity;mammalian synthetic biology;Synthetic gene circuit
29
1982;1998;1999;2003;2005;2007;2008;2010;2011;2012;2013;2014;2015;2016
18
MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA;Weizmann Inst Sci, Dept Mat & Interfaces, IL-76100 Rehovot, Israel
Proc. Natl. Acad. Sci. U. S. A.
Bar-Ziv, Roy H
NATL ACAD SCIENCES
,;a;acting;activation;also;amplification;an;analysis;and;are;as;assay;background;be;because;between;beyond;by;cancer;cell;cell-culture;cells;cellular;circuits;combinatorial;control;controlled;could;decision-making;detrimental;efficiently;emerging;enhanced;environment;error;escape;even;expression;far;few;function;gain;gate;gene;have;here;heterogeneous;highly;however;implement;in;inherent;integration;is;killing;light;logic;loss;malignant;Markers;means;measure;might;minimal;model;molecular;multiple;must;normal;of;on;ones;operating;optimized;our;parameters;populations;promoters;rates;remained;response;reveals;sensitive;sensitivity;show;single-cell;so;specificity;state;such;suggests;synthetic;target;that;the;this;threshold;to;tradeoff;tumor-mimicking;tunable;tuned;two;unexplored;variability;versatile;we;with
MIT;Weizmann Inst Sci
Synthetic gene circuits are emerging as a versatile means to target cancer with enhanced specificity by combinatorial integration of multiple expression markers. Such circuits must also be tuned to be highly sensitive because escape of even a few cells might be detrimental. However, the error rates of decision-making circuits in light of cellular variability in gene expression have so far remained unexplored. Here, we measure the single-cell response function of a tunable logic AND gate acting on two promoters in heterogeneous cell populations. Our analysis reveals an inherent tradeoff between specificity and sensitivity that is controlled by the AND gate amplification gain and activation threshold. We implement a tumor-mimicking cell-culture model of cancer cells emerging in a background of normal ones, and show that molecular parameters of the synthetic circuits control specificity and sensitivity in a killing assay. This suggests that, beyond the inherent tradeoff, synthetic circuits operating in a heterogeneous environment could be optimized to efficiently target malignant state with minimal loss of specificity.
A-9754-2016
BIOLOGY;COMPUTATION;FRAMEWORK;GENERATION;MAMMALIAN-CELLS;SYSTEM;T-CELLS
0
null
cancer gene therapy;cell-state targeting;cellular heterogeneity;mammalian synthetic biology;synthetic gene circuits
6
BIOLOGY;CANCER GENE-THERAPY;cell-state targeting;cellular heterogeneity;COMPUTATION;FRAMEWORK;GENERATION;MAMMALIAN-CELLS;mammalian synthetic biology;synthetic gene circuits;SYSTEM;T-CELLS
WOS:000380224500053
MIT, Cambridge, MA USA;Univ Paris, Paris, France;Weizmann Inst Sci, Rehovot, Israel
France;Israel;USA
2,016
null
0000-0001-6495-4741;0000-0002-6284-1708
null
null
English
null
ACS SYNTH BIOL;BIOCHEM J;BIOTECHNOL BIOENG;CANCER RES;CELL;J BIOMED BIOTECHNOL;J CELL COMMUN SIGNAL;J CLIN IMMUNOL;J MOL RECOGNIT;J VIROL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT MATER;NAT REV GENET;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;PHYS BIOL;RADIOLOGY;SCI TRANSL MED;SCIENCE;TRENDS IMMUNOL
Bar-Ziv, Roy H;Morel, Mathieu;Nissim, Lior;Rotter, Varda;Shtrahman, Roman
2024-03-11 ER
Anderson, J C;Ang, J;Ausländer, S;Bacchus, W;Barak, Y;Bonnet, J;Buganim, Y;Conde, J;Costello, J C;Daniel, R;Dull, T;Eldar, A;Gaber, R;Hanley, J A;Karpol, A;Kelm, J M;Khalil, A S;Kloss, C C;Lienert, F;Lohmueller, J J;Meacham, C E;Milyavsky, M;Nissim, L;Nyga, A;Robson, T;Roybal, K T;Rubsam, L Z;Russell, S J;Srivastava, S;Tamsir, A;Tanner, K;Van 'T Veer, L J;Weber, W;Wilkie, S;Xie, Z;Zomer, A
DR9NX
Cambridge, MA USA;Rehovot, Israel.
26
null
3
null
27,385,823
Bar-Ziv, Roy H;Morel, Mathieu;Nissim, Lior;Rotter, Varda;Shtrahman, Roman
P NATL ACAD SCI USA
Cambridge, MA USA;Paris, France;Rehovot, Israel
Fleck, O;Freke, G;Hernandez, A D;Homma, T;Kis, Z;Krams, R;Lai, Z X;Pedrigi, R M;Rodin, T;Towhidi, L;Zafar, A
10.1038/srep29643
29643
HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
3rej592m5t1t3805p1u443d5nq605d109w
Development of a synthetic gene network to modulate gene expression by mechanical forces
Imperial Coll London
null
Krams, R (corresponding author), Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England.
null
Fleck, Oliver;Freke, Grace;Hernandez, Armando Del Rio;Homma, Takayuki;Kis, Zoltan;Krams, Rob;Lai, Zhangxing;Pedrigi, Ryan M;Rodin, Tania;Towhidi, Leila;Zafar, Asma
Multidisciplinary Sciences
British Hearth Foundation [RG/11/13/29055]; Department of Bioengineering, Imperial College London; British Heart Foundation [PG/15/49/31595, RG/11/13/29055] Funding Source: researchfish
WOS
Krams, R
Govt Coll Univ, Lahore, Pakistan;Imperial Coll London, London, England;Kyoto Univ, Kyoto, Japan;Natl Univ Singapore, Singapore, Singapore;UCL, London, England;Univ Cambridge, Cambridge, England
6
a;by;Development;expression;forces;gene;mechanical;modulate;network;of;synthetic;to
4
del Río Hernández, Armando E;Kis, Zoltan
NATURE PORTFOLIO
Govt Coll Univ, Govt Coll Univ, Katchery Rd, Lahore 54000, Pakistan;Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England;Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Yoshida Ushinomiya Cho, Kyoto 6068501, Japan;Natl Univ Singapore, Dept Biomed Engn, 4 Engn Dr 3, Singapore 117575, Singapore;Natl Univ Singapore, Dept Mech Engn, 9 Engn Dr 1, Singapore 117575, Singapore;UCL, Inst Child Hlth, 30 Guilford St, London WC1N 1EH, England;Univ Cambridge, Dept Engn, Trumpington St, Cambridge CB2 1PZ, England
Article
Imperial Coll London
BERLIN
null
null
Govt Coll Univ;Imperial Coll London;Kyoto Univ;Natl Univ Singapore;UCL;Univ Cambridge
British Heart Foundation;British Hearth Foundation;Department of Bioengineering, Imperial College London
Krams, R (corresponding author), Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England.
null
Fleck, Oliver;Freke, Grace;Hernandez, Armando Del Rio;Homma, Takayuki;Kis, Zoltan;Krams, Rob;Lai, Zhangxing;Pedrigi, Ryan M;Rodin, Tania;Towhidi, Leila;Zafar, Asma
13
7
379,392,100,001
British Heart Foundation [PG/15/49/31595, RG/11/13/29055] Funding Source: researchfish;British Hearth Foundation [RG/11/13/29055];Department of Bioengineering, Imperial College London
Japan;Pakistan;Singapore;UK
SCIENTIFIC REPORTS
UK
null
null
Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England
2045-2322
Fleck, O;Freke, G;Hernandez, A D;Homma, T;Kis, Z;Krams, R;Lai, Z X;Pedrigi, R M;Rodin, T;Towhidi, L;Zafar, A
JUL 12
r.krams@imperial.ac.uk
development;gene expression;mechanical forces;synthetic gene network
11
J
Science & Technology - Other Topics
(mammalian) cells;60%;ACTING BRADYKININ-ANTAGONIST;activation;ASSAYS;atheroprotective transcription factor;ATHEROSCLEROSIS;B2 RECEPTOR;body;CELL-LINES;cells;development;electroporation;endothelial cell shear stress levels;ENDOTHELIAL SHEAR-STRESS;exposes cells;expression;first mammalian mechanosensitive synthetic gene network;FLOW;flow channel floor;flow setup;function;functional gene network;gene expression;gene network;gene network activation;gene network functionality;graded control;hard-to-transfect mammalian cells;high proportion;HOE-140;hybrid transfection procedure;increasing shear stress;KRUPPEL-LIKE FACTOR-2;length;little work;majority;mammalian antibiotic selection;mammalian cells;mechanical forces;mechanical stimuli;mechanosensor activity;MECHANOTRANSDUCTION;new approach mechanosyngenetics;plasmids replication;procedure takes 1 week;second electroporation;shear stress;shear stress magnitude;synthetic gene network;technique;WALL SHEAR
Kis, Z
ACTING BRADYKININ-ANTAGONIST;ATHEROSCLEROSIS;B2 RECEPTOR;CELL-LINES;ENDOTHELIAL SHEAR-STRESS;FLOW;HOE-140;KRUPPEL-LIKE FACTOR-2;MECHANOTRANSDUCTION;WALL SHEAR
null
[Kis, Zoltan; Rodin, Tania; Zafar, Asma; Lai, Zhangxing; Freke, Grace; Fleck, Oliver; Hernandez, Armando Del Rio; Towhidi, Leila; Pedrigi, Ryan M.; Homma, Takayuki; Krams, Rob] Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England. [Zafar, Asma] Govt Coll Univ, Govt Coll Univ, Katchery Rd, Lahore 54000, Pakistan. [Lai, Zhangxing] Natl Univ Singapore, Dept Mech Engn, 9 Engn Dr 1, Singapore 117575, Singapore. [Lai, Zhangxing] Natl Univ Singapore, Dept Biomed Engn, 4 Engn Dr 3, Singapore 117575, Singapore. [Freke, Grace] UCL, Inst Child Hlth, 30 Guilford St, London WC1N 1EH, England. [Fleck, Oliver] Univ Cambridge, Dept Engn, Trumpington St, Cambridge CB2 1PZ, England. [Homma, Takayuki] Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Yoshida Ushinomiya Cho, Kyoto 6068501, Japan.
Funding from British Hearth Foundation (RG/11/13/29055) and PhD Studentship (to Z.K.) from Department of Bioengineering, Imperial College London are gratefully acknowledged.
(mammalian) cells;60%;activation;assays;atheroprotective transcription factor;body;cells;electroporation;endothelial cell shear stress levels;exposes cells;expression;first mammalian mechanosensitive synthetic gene network;flow channel floor;flow setup;function;functional gene network;gene expression;gene network;gene network activation;gene network functionality;graded control;hard-to-transfect mammalian cells;high proportion;hybrid transfection procedure;increasing shear stress;length;little work;majority;mammalian antibiotic selection;mammalian cells;mechanical forces;mechanical stimuli;mechanosensor activity;new approach mechanosyngenetics;plasmids replication;procedure takes 1 week;second electroporation;shear stress;shear stress magnitude;technique
10.1001/jama.282.21.2035;10.1002/0471142727.mb0903s62;10.1002/bit.22406;10.1007/s10439-005-8774-0;10.1007/s12033-007-0007-3;10.1016/0014-5793(90)80166-G;10.1016/0024-3205(94)00557-5;10.1016/j.bbamem.2006.10.021;10.1016/j.bios.2007.12.009;10.1016/j.cub.2014.04.027;10.1016/j.devcel.2005.12.006;10.1016/j.jacc.2007.02.059;10.1016/j.jbiomech.2014.03.031;10.1016/j.mvr.2004.08.002;10.1016/j.pbiomolbio.2014.06.009;10.1016/j.semcdb.2014.06.018;10.1016/j.ymeth.2003.11.009;10.1016/S0008-6363(98)00074-1;10.1016/S0014-2999(98)00165-4;10.1038/nrm2597;10.1038/sj.gt.3300867;10.1055/s-0037-1616937;10.1073/pnas.0607224103;10.1073/pnas.0710487105;10.1073/pnas.130192197;10.1073/pnas.1313364111;10.1073/pnas.88.17.7724;10.1073/pnas.89.12.5547;10.1074/jbc.271.50.32366;10.1074/jbc.M800362200;10.1084/jem.20031132;10.1089/ars.2010.3679;10.1093/cvr/cvt108;10.1097/CMR.0b013e3283390696;10.1097/HCO.0b013e3282f07548;10.1098/rspb.1971.0019;10.1098/rstb.2007.2128;10.1111/j.1365-2796.2006.01620.x;10.1111/j.1476-5381.1991.tb12248.x;10.1111/j.1476-5381.1991.tb12249.x;10.1111/j.1476-5381.1994.tb13130.x;10.1111/micc.12119;10.1128/MCB.20.18.6837-6848.2000;10.1136/gut.2010.220913;10.1146/annurev.bioeng.6.040803.140203;10.1152/physrev.00047.2009;10.1161/01.HYP.37.2.703;10.1161/01.RES.53.4.502;10.1161/ATVBAHA.114.303426;10.1161/CIRCULATIONAHA.104.525774;10.1161/CIRCULATIONAHA.105.590018;10.1161/CIRCULATIONAHA.110.005108;10.1172/JCI200215493;10.1177/1947603513495889;10.3791/50171
Imperial Coll London
Fleck, O;Freke, G;Hernandez, A D;Homma, T;Kis, Z;Krams, R;Lai, Z X;Pedrigi, R M;Rodin, T;Towhidi, L;Zafar, A
Kis, Z: Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England
del rio hernandez, armando e;del Río Hernández, Armando E;Kis, Zoltan
PG/15/49/31595;RG/11/13/29055
62
null
UK
Govt Coll Univ;Imperial Coll London;Kyoto Univ;Natl Univ Singapore;UCL;Univ Cambridge
Kis, Zoltan
Green Published, Green Submitted, gold, Green Accepted
ACTING BRADYKININ-ANTAGONIST;ATHEROSCLEROSIS;B2 RECEPTOR;CELL-LINES;ENDOTHELIAL SHEAR-STRESS;FLOW;HOE-140;KRUPPEL-LIKE FACTOR-2;MECHANOTRANSDUCTION;WALL SHEAR
Kis, Zoltan; Rodin, Tania; Zafar, Asma; Lai, Zhangxing; Freke, Grace; Fleck, Oliver; Hernandez, Armando Del Rio; Towhidi, Leila; Pedrigi, Ryan M.; Homma, Takayuki; Krams, Rob;
null
Govt Coll Univ, Govt Coll Univ, Katchery Rd, Lahore 54000, Pakistan;Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England;Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Yoshida Ushinomiya Cho, Kyoto 6068501, Japan;Natl Univ Singapore, Dept Biomed Engn, 4 Engn Dr 3, Singapore 117575, Singapore;Natl Univ Singapore, Dept Mech Engn, 9 Engn Dr 1, Singapore 117575, Singapore;UCL, Inst Child Hlth, 30 Guilford St, London WC1N 1EH, England;Univ Cambridge, Dept Engn, Trumpington St, Cambridge CB2 1PZ, England
Govt Coll Univ, Govt Coll Univ, Katchery Rd, Lahore 54000, Pakistan;Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England;Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Yoshida Ushinomiya Cho, Kyoto 6068501, Japan;Natl Univ Singapore, Dept Biomed Engn, 4 Engn Dr 3, Singapore 117575, Singapore;Natl Univ Singapore, Dept Mech Engn, 9 Engn Dr 1, Singapore 117575, Singapore;UCL, Inst Child Hlth, 30 Guilford St, London WC1N 1EH, England;Univ Cambridge, Dept Engn, Trumpington St, Cambridge CB2 1PZ, England
null
null
null
1971;1983;1990;1991;1992;1994;1996;1998;1999;2000;2001;2002;2003;2004;2005;2006;2007;2008;2009;2010;2011;2013;2014;2015
4
Imperial Coll London, Dept Bioengn, Exhibit Rd, London SW7 2AZ, England
Sci Rep
Krams, Rob
NATURE PORTFOLIO
(mammalian);,;1;60%;a;activation;activity;address;allows;along;an;and;antibiotic;approach;are;as;assays;atheroprotective;been;body;but;by;call;cell;cells;channel;control;currently;develop;developed;directly;done;drive;easily;electroporation;endothelial;exposes;expression;factor;first;floor;flow;forces;function;functional;functionality;furthermore;gene;graded;hard-to-transfect;has;high;highly;hybrid;impossible;in;increasing;insert;into;involves;is;it;length;levels;linearly;little;logarithmically;magnitude;majority;mammalian;mechanical;mechanosensitive;mechanosensor;mechanosyngenetics;modular;modulate;monitor;needs;network;new;of;our;over;plasmids;procedure;proportion;replication;scalable;second;selection;sensitive;setup;shear;stimuli;stress;synthetic;takes;technique;test;that;the;these;this;to;transcription;transfection;use;varied;was;we;week;with;work;yielded
Imperial Coll London
The majority of (mammalian) cells in our body are sensitive to mechanical forces, but little work has been done to develop assays to monitor mechanosensor activity. Furthermore, it is currently impossible to use mechanosensor activity to drive gene expression. To address these needs, we developed the first mammalian mechanosensitive synthetic gene network to monitor endothelial cell shear stress levels and directly modulate expression of an atheroprotective transcription factor by shear stress. The technique is highly modular, easily scalable and allows graded control of gene expression by mechanical stimuli in hard-to-transfect mammalian cells. We call this new approach mechanosyngenetics. To insert the gene network into a high proportion of cells, a hybrid transfection procedure was developed that involves electroporation, plasmids replication in mammalian cells, mammalian antibiotic selection, a second electroporation and gene network activation. This procedure takes 1 week and yielded over 60% of cells with a functional gene network. To test gene network functionality, we developed a flow setup that exposes cells to linearly increasing shear stress along the length of the flow channel floor. Activation of the gene network varied logarithmically as a function of shear stress magnitude.
D-3555-2012;H-3611-2016;N-4262-2013
ACTING BRADYKININ-ANTAGONIST;ATHEROSCLEROSIS;B2 RECEPTOR;CELL-LINES;ENDOTHELIAL SHEAR-STRESS;FLOW;HOE-140;KRUPPEL-LIKE FACTOR-2;MECHANOTRANSDUCTION;WALL SHEAR
0
null
null
10
ACTING BRADYKININ-ANTAGONIST;ATHEROSCLEROSIS;B2 RECEPTOR;CELL-LINES;ENDOTHELIAL SHEAR-STRESS;FLOW;HOE-140;KRUPPEL-LIKE FACTOR-2;MECHANOTRANSDUCTION;WALL SHEAR
WOS:000379392100001
Govt Coll Univ, Lahore, Pakistan;Imperial Coll London, London, England;Kyoto Univ, Kyoto, Japan;Natl Univ Singapore, Singapore, Singapore;UCL, London, England;Univ Cambridge, Cambridge, England
Japan;Pakistan;Singapore;UK
2,016
null
0000-0001-5062-8910;0000-0002-6598-8369
null
null
English
null
ANN BIOMED ENG;ANNU REV BIOMED ENG;ANTIOXID REDOX SIGN;ARTERIOSCL THROM VAS;BBA-BIOMEMBRANES;BIORHEOLOGY;BIOSENS BIOELECTRON;BIOTECHNOL BIOENG;BRIT J PHARMACOL;CARDIOVASC RES;CARDIOVASCULAR DIS;CARTILAGE;CIRC RES;CIRCULATION;CURR BIOL;CURR OPIN CARDIOL;Curr Protoc Mol Biol;DEV CELL;EUR J PHARMACOL;FEBS LETT;GENE THER;GLOBAL STATUS REPORT ON VIOLENCE PREVENTION 2014;GUT;HAMOSTASEOLOGIE;HYPERTENSION;J AM COLL CARDIOL;J BIOL CHEM;J BIOMECH;J CLIN INVEST;J EXP MED;J INTERN MED;J TISSUE ENG REGENER;JAMA-J AM MED ASSOC;JOVE-J VIS EXP;LIFE SCI;MELANOMA RES;METHODS;MICROCIRCULATION;MICROVASC RES;MOL BIOTECHNOL;MOL CELL BIOL;NAT REV MOL CELL BIO;P NATL ACAD SCI USA;PFLUGERS ARCH EUROPE;PHILOS T R SOC B;PHYSIOL REV;PROC R SOC SER B-BIO;PROG BIOPHYS MOL BIO;SEMIN CELL DEV BIOL
Fleck, Oliver;Freke, Grace;Hernandez, Armando Del Rio;Homma, Takayuki;Kis, Zoltan;Krams, Rob;Lai, Zhangxing;Pedrigi, Ryan M;Rodin, Tania;Towhidi, Leila;Zafar, Asma
2024-03-11 ER
Anishkin, A;Barnea, G;Bewick G. S.;Blaukat, A;Boon, R A;Buchmann, A;Buckwalter, J A;Carapuca, E;Caro, C G;Chachisvilis, M;Chatzizisis, Y S;Cheng, C;Chiu, J J;Davies, P F;Dengler, R;Duscher, D;Fedorchak, G R;Feletou, M;Fernandes, L;Frueh, J;Gomez-Martinez, M;Gossen, M;Gracia-Sancho, J;Gresch, O;Hock, F J;Jaalouk, D E;Kennard, M L;Kim, J A;Kinderlerer, A R;Kobilka, B K;Lechardeur, D;Majkut, S;Malek, A M;Mceachern, A E;Ng, C P;Nigro, P;Orr, A W;Pedrigi R. M.;Pedrigi, R M;Potter Huntington;Regoli, D;Roth, C M;Ruggiu A.;Samijo, S K;Schanstra, J P;Selvan, S R;Sen-Banerjee, S;Senbanerjee, S;Tarbell, J M;Urlinger, S;Volkers L.;White, C R;Who;Wirth, K;World Health Organization;Wragg, J W;Wu, W;Zarins, C K
DQ7MR
London, England
4
null
6
null
27,404,994
Fleck, Oliver;Freke, Grace;Hernandez, Armando Del Rio;Homma, Takayuki;Kis, Zoltan;Krams, Rob;Lai, Zhangxing;Pedrigi, Ryan M;Rodin, Tania;Towhidi, Leila;Zafar, Asma
SCI REP-UK
Cambridge, England;Kyoto, Japan;Lahore, Pakistan;London, England;Singapore, Singapore
Balázsi, G;Bódi, Z;Charlebois, D A;Diao, J C;Nevozhay, D;Pál, C
10.1021/acssynbio.5b00154
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
2t4149531y1f251u1jv4l2z5v5by6ey5333q
Efflux Pump Control Alters Synthetic Gene Circuit Function
Univ Texas MD Anderson Canc Ctr
null
Balázsi, G (corresponding author), SUNY Stony Brook, Dept Biomed Engn, Z-5281, Stony Brook, NY 11794 USA.;Balázsi, G (corresponding author), SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Laufer Ctr 115C, Z-5252, Stony Brook, NY 11794 USA.;Balázsi, G (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA.
null
Balazsi, Gabor;Bodi, Zoltan;Charlebois, Daniel A;Diao, Junchen;Nevozhay, Dmitry;Pal, Csaba
Biochemical Research Methods
NIH Director's New Innovator Award Program [1DP2 OD006481-01]; Laufer Center for Physical AMP; Quantitative Biology; Lendiilet Program of the Hungarian Academy of Sciences; European Research Council [ERC-2007-StG]; University of Texas Graduate School of Biomedical Sciences at Houston; Ministry of Education and Science, Russian Federation [1326]; Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship [PDF-453977-2014]
WOS
Balázsi, G
Far Eastern Fed Univ, Vladivostok, Russia;Hungarian Acad Sci, Szeged, Hungary;SUNY Stony Brook, Stony Brook, NY USA;Univ Texas MD Anderson Canc Ctr, Houston, TX USA
5
Alters;circuit;control;efflux;function;gene;Pump;synthetic
3
Balazsi, Gabor;Charlebois, Daniel
AMER CHEMICAL SOC
Far Eastern Fed Univ, Sch Biomed, 8 Sukhanova St, Vladivostok 690950, Russia;Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary;SUNY Stony Brook, Dept Biomed Engn, Z-5281, Stony Brook, NY 11794 USA;SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Laufer Ctr 115C, Z-5252, Stony Brook, NY 11794 USA;Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA;Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA.; Balázsi, G (corresponding author), SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Laufer Ctr 115C, Z-5252, Stony Brook, NY 11794 USA.; Balázsi, G (corresponding author), SUNY Stony Brook, Dept Biomed Engn, Z-5281, Stony Brook, NY 11794 USA
Article
Univ Texas MD Anderson Canc Ctr;SUNY Stony Brook
WASHINGTON
null
null
Far Eastern Fed Univ;Hungarian Acad Sci;SUNY Stony Brook;Univ Texas MD Anderson Canc Ctr
European Research Council;Laufer Center for Physical AMP;Lendiilet Program of the Hungarian Academy of Sciences;Ministry of Education and Science, Russian Federation;Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship;NIH Director's New Innovator Award Program;Quantitative Biology;University of Texas Graduate School of Biomedical Sciences at Houston
Balázsi, G (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA.; Balázsi, G (corresponding author), SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Laufer Ctr 115C, Z-5252, Stony Brook, NY 11794 USA.; Balázsi, G (corresponding author), SUNY Stony Brook, Dept Biomed Engn, Z-5281, Stony Brook, NY 11794 USA.
631
Balazsi, Gabor;Bodi, Zoltan;Charlebois, Daniel A;Diao, Junchen;Nevozhay, Dmitry;Pal, Csaba
25
5
380,183,000,011
European Research Council [ERC-2007-StG];Laufer Center for Physical AMP;Lendiilet Program of the Hungarian Academy of Sciences;Ministry of Education and Science, Russian Federation [1326];Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship [PDF-453977-2014];NIH Director's New Innovator Award Program [1DP2 OD006481-01];Quantitative Biology;University of Texas Graduate School of Biomedical Sciences at Houston
Hungary;Russia;USA
ACS SYNTHETIC BIOLOGY
USA;USA.;
null
null
Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA
2161-5063
Balázsi, G;Bódi, Z;Charlebois, D A;Diao, J C;Nevozhay, D;Pál, C
JUL
gabor.balazsi@stonybrook.edu
efflux Pump Control;synthetic gene circuit function
6
J
Biochemistry & Molecular Biology
ABC efflux pumps;ABC-TRANSPORTERS;altered dose-responses;another aspect;ATP-binding cassette (ABC) protein family;biofuels;BIOLOGY;Change;chemicals;controlled secretion;COUPLED CHEMICAL-REACTIONS;dose-responses;drive;DRUG-RESISTANCE;efflux;efflux pump;efflux Pump Control;efflux pump function;efflux pumps;expression;FEEDBACK;function;gene circuit dynamics;gene circuit function;Gene circuits;implicit feedback;inducer;intracellular inducer molecules;mathematical modeling;new biological systems;new circumstances;noise;one aspect;original gene circuits;overall;pdr5p;pharmaceuticals;poorly understood;predefined purposes;predictions;quantitative modeling;reduced regulator gene expression;Saccharomyces cerevisiae;SACCHAROMYCES-CEREVISIAE;SINGLE-CELL;stochastic simulation;synthetic biology aims;Synthetic gene circuit;synthetic gene circuit function;synthetic gene circuits;tetracycline family molecules;understanding synthetic gene circuit function;unexplained;used two synthetic gene circuits inducible;utility;will;yeast ABC pump (Pdr5p);YEAST-CELLS
Diao, J C
ABC-TRANSPORTERS;BIOLOGY;COUPLED CHEMICAL-REACTIONS;DRUG-RESISTANCE;efflux pump;EXPRESSION;FEEDBACK;NOISE;SACCHAROMYCES-CEREVISIAE;SINGLE-CELL;stochastic simulation;Synthetic gene circuit;YEAST-CELLS
619
[Diao, Junchen; Nevozhay, Dmitry; Balazsi, Gabor] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA. [Charlebois, Daniel A.; Balazsi, Gabor] SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Laufer Ctr 115C, Z-5252, Stony Brook, NY 11794 USA. [Nevozhay, Dmitry] Far Eastern Fed Univ, Sch Biomed, 8 Sukhanova St, Vladivostok 690950, Russia. [Bodi, Zoltan; Pal, Csaba] Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary. [Balazsi, Gabor] SUNY Stony Brook, Dept Biomed Engn, Z-5281, Stony Brook, NY 11794 USA.
We thank W.-K. Huh for kindly sharing the PDR5::GFP fusion, and M. Bennett, M. Lorenz, G. May, T. F. Cooper and G. Peng for helpful discussions. This research was supported by the NIH Director's New Innovator Award Program (1DP2 OD006481-01) and by the Laufer Center for Physical & Quantitative Biology to GB; by the Lendiilet Program of the Hungarian Academy of Sciences, and the European Research Council (ERC-2007-StG) to CP; by the University of Texas Graduate School of Biomedical Sciences at Houston to JD; Program # 1326 of the Ministry of Education and Science, Russian Federation to DN; and by a Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship [Grant no: PDF-453977-2014] to DC.
ABC efflux pumps;altered dose-responses;another aspect;ATP-binding cassette (ABC) protein family;biofuels;change;chemicals;controlled secretion;dose-responses;drive;efflux;efflux pump;efflux pump function;efflux pumps;expression;function;gene circuit dynamics;gene circuit function;gene circuits;implicit feedback;inducer;intracellular inducer molecules;mathematical modeling;new biological systems;new circumstances;one aspect;original gene circuits;overall;pdr5p;pharmaceuticals;poorly understood;predefined purposes;predictions;quantitative modeling;reduced regulator gene expression;Saccharomyces cerevisiae;synthetic biology aims;synthetic gene circuits;tetracycline family molecules;understanding synthetic gene circuit function;unexplained;used two synthetic gene circuits inducible;utility;will;yeast ABC pump (Pdr5p)
10.1002/elps.200900244;10.1002/yea.320110408;10.1007/978-1-61779-086-7_5;10.1016/0021-9991(76)90041-3;10.1016/j.cell.2009.12.001;10.1016/j.cell.2014.02.039;10.1016/j.copbio.2014.01.001;10.1016/j.febslet.2009.10.071;10.1016/j.molcel.2006.11.003;10.1016/j.molcel.2014.04.022;10.1016/j.ymben.2015.11.005;10.1016/S0924-8579(03)00203-6;10.1021/bi100394j;10.1021/j100540a008;10.1021/sb300094q;10.1038/35002125;10.1038/35002131;10.1038/35014651;10.1038/msb.2011.21;10.1038/msb.2011.49;10.1038/msb4100081;10.1038/nature01546;10.1038/nature02026;10.1038/nature04785;10.1038/nature07389;10.1038/nature07616;10.1038/nature11516;10.1038/nbt.1536;10.1038/nbt.2510;10.1038/nbt1270;10.1038/ncb2085;10.1038/nchembio.1519;10.1038/nchembio.218;10.1038/ncomms2471;10.1038/ng869;10.1038/nrg2775;10.1038/nrg3227;10.1038/nrm2698;10.1073/pnas.0608451104;10.1073/pnas.0736140100;10.1073/pnas.0809901106;10.1074/jbc.271.49.31543;10.1074/jbc.M806446200;10.1089/mdr.1998.4.143;10.1093/nar/gkq091;10.1103/PhysRevE.89.052708;10.1126/science.1070919;10.1126/science.1205527;10.1126/science.1207084;10.1371/journal.pbio.0020137;10.1371/journal.pcbi.1000257;10.1371/journal.pcbi.1003229;10.3389/fmicb.2012.00360;[10.1038/NMETH.2926, 10.1038/nmeth.2926]
Univ Texas MD Anderson Canc Ctr
Balázsi, G;Bódi, Z;Charlebois, D A;Diao, J C;Nevozhay, D;Pál, C
Diao, J C: Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA
Charlebois, Daniel;Nevozhay, Dmitry
1326;1DP2 OD006481-01;ERC-2007-StG;PDF-453977-2014
55
null
USA
Far Eastern Fed Univ;Hungarian Acad Sci;SUNY Stony Brook;Univ Texas MD Anderson Canc Ctr
Diao, Junchen
Green Accepted
ABC-TRANSPORTERS;BIOLOGY;COUPLED CHEMICAL-REACTIONS;DRUG-RESISTANCE;EXPRESSION;FEEDBACK;NOISE;SACCHAROMYCES-CEREVISIAE;SINGLE-CELL;YEAST-CELLS
Diao, Junchen; Charlebois, Daniel A.; Nevozhay, Dmitry; Bodi, Zoltan; Pal, Csaba; Balazsi, Gabor;
null
Far Eastern Fed Univ, Sch Biomed, 8 Sukhanova St, Vladivostok 690950, Russia;Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary;SUNY Stony Brook, Dept Biomed Engn, Z-5281, Stony Brook, NY 11794 USA;SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Laufer Ctr 115C, Z-5252, Stony Brook, NY 11794 USA;Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA
Far Eastern Fed Univ, Sch Biomed, 8 Sukhanova St, Vladivostok 690950, Russia;Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary;SUNY Stony Brook, Dept Biomed Engn, Z-5281, Stony Brook, NY 11794 USA;SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Laufer Ctr 115C, Z-5252, Stony Brook, NY 11794 USA;Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA
null
efflux pump;feedback;stochastic simulation;Synthetic gene circuit
7
1976;1977;1995;1996;1998;2000;2001;2002;2003;2004;2006;2007;2008;2009;2010;2011;2012;2013;2014;2016
13
SUNY Stony Brook, Dept Biomed Engn, Z-5281, Stony Brook, NY 11794 USA;SUNY Stony Brook, Louis & Beatrice Laufer Ctr Phys & Quantitat Biol, Laufer Ctr 115C, Z-5252, Stony Brook, NY 11794 USA;Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Unit 950, 7435 Fannin St, Houston, TX 77054 USA
ACS Synth. Biol.
Balazsi, Gabor
AMER CHEMICAL SOC
(ABC);(Pdr5p);,;a;ABC;achieve;addition;aims;also;alter;altered;an;and;another;are;as;aspect;ATP-binding;attributed;be;biofuels;biological;biology;by;can;cassette;cerevisiae;change;chemicals;circuit;circuits;circumstances;control;controlled;could;demonstrate;design;dose-responses;drive;dynamics;efflux;experimentally;explain;expression;family;feedback;for;from;fully;function;gene;here;highlight;how;however;implicit;in;indicated;inducer;inducible;intracellular;introduce;mathematical;modeling;molecules;new;of;one;or;original;other;out;overall;pdr5p;pharmaceuticals;poorly;predefined;predictions;protein;pump;pumping;pumps;purposes;quantitative;reduced;regulate;regulating;regulator;remained;Saccharomyces;secretion;substantially;such;synthetic;systems;tetracycline;that;the;these;this;to;two;understanding;understood;unexplained;used;utility;validated;ways;we;were;while;will;yeast
SUNY Stony Brook;Univ Texas MD Anderson Canc Ctr
Synthetic biology aims to design new biological systems for predefined purposes, such as the controlled secretion of biofuels, pharmaceuticals, or other chemicals. Synthetic gene circuits regulating an efflux pump from the ATP-binding cassette (ABC) protein family could achieve this. However, ABC efflux pumps can also drive out intracellular inducer molecules that control the gene circuits. This will introduce an implicit feedback that could alter gene circuit function in ways that are poorly understood. Here, we used two synthetic gene circuits inducible by tetracycline family molecules to regulate the expression of a yeast ABC pump (Pdr5p) that pumps out the inducer. Pdr5p altered the dose-responses of the original gene circuits substantially in Saccharomyces cerevisiae. While one aspect of the change could be attributed to the efflux pumping function of Pdr5p, another aspect remained unexplained. Quantitative modeling indicated that reduced regulator gene expression in addition to efflux pump function could fully explain the altered dose-responses. These predictions were validated experimentally. Overall, we highlight how efflux pumps can alter gene circuit dynamics and demonstrate the utility of mathematical modeling in understanding synthetic gene circuit function in new circumstances.
D-7251-2017;R-8264-2016
ABC TRANSPORTER;BIOLOGY;COUPLED CHEMICAL-REACTIONS;DRUG-RESISTANCE;EXPRESSION;FEEDBACK;NOISE;SACCHAROMYCES-CEREVISIAE;SINGLE-CELL;YEAST-CELLS
0
null
efflux pump;feedback;stochastic simulation;Synthetic gene circuit
13
SACCHAROMYCES-CEREVISIAE;ABC TRANSPORTER;BIOLOGY;COUPLED CHEMICAL-REACTIONS;DRUG-RESISTANCE;EFFLUX PUMPS;EXPRESSION;FEEDBACK;NOISE;SINGLE-CELL;stochastic simulation;synthetic gene circuits;YEAST-CELLS
WOS:000380183000011
Far Eastern Fed Univ, Vladivostok, Russia;Hungarian Acad Sci, Szeged, Hungary;SUNY Stony Brook, Stony Brook, NY USA;Univ Texas MD Anderson Canc Ctr, Houston, TX USA
Hungary;Russia;USA
2,016
null
0000-0001-7426-1789;0000-0002-6865-5818
null
null
English
null
ACS SYNTH BIOL;BIOCHEMISTRY-US;CELL;CURR OPIN BIOTECH;ELECTROPHORESIS;FEBS LETT;FRONT MICROBIOL;INT J ANTIMICROB AG;J BIOL CHEM;J COMPUT PHYS;J MOL MICROB BIOTECH;J PHYS CHEM-US;METAB ENG;METHODS MOL BIOL;MICROB DRUG RESIST;MOL CELL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CELL BIOL;NAT CHEM BIOL;NAT COMMUN;NAT GENET;NAT METHODS;NAT REV GENET;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV E;PLOS BIOL;PLOS COMPUT BIOL;SCIENCE;YEAST
Balazsi, Gabor;Bodi, Zoltan;Charlebois, Daniel A;Diao, Junchen;Nevozhay, Dmitry;Pal, Csaba
2024-03-11 ER
Airoldi, E M;Ananthaswamy, N;Becskei, A;Blake, W J;Bleris, L;Boyarskiy, S;Brophy, J A N;Charlebois, D A;Dublanche, Y;Dunlop, M J;Eldakak, A;Ellis, T;Elowitz, M B;Fraser, H B;Garcia-Bernardo, J;Gardner, T S;Gietz, R D;Gillespie, D T;Harrison, M E;Huh, W K;Ino, K;Khalil, A S;Klumpp, S;Kolaczkowski, M;Lage, H;Levy, S;Lu, P;Moon, T S;Murphy, K F;Nandagopal, N;Nevozhay, D;Newman, J R S;Nielsen, J;Nissim, L;Ozbudak, E M;Purnick, P E M;Rogers, B;Sauna, Z E;Simpson, M L;Siuti, P;Slusarczyk, A L;Stephanopoulos, G;Stricker, J;Tan, C;Tigges, M;Way, J C;Xie, Z
DR8XZ
Houston, TX USA.;Stony Brook, NY USA;Stony Brook, NY USA.
16
null
4
null
27,111,147
Balazsi, Gabor;Bodi, Zoltan;Charlebois, Daniel A;Diao, Junchen;Nevozhay, Dmitry;Pal, Csaba
ACS SYNTH BIOL
Houston, TX USA;Stony Brook, NY USA;Szeged, Hungary;Vladivostok, Russia
Aycilar-Kucukgoze, I;Bovenberg, R A L;Gorochowski, T E;Ignatova, Z;Roubos, J A
10.1021/acssynbio.6b00040
null
1155 16TH ST, NW, WASHINGTON, DC 20036 USA
285k2r4f154l1o81m2cl2w2e580183h3y5u3s
A Minimal Model of Ribosome Allocation Dynamics Captures Trade-offs in Expression between Endogenous and Synthetic Genes
DSM Biotechnol Ctr
null
Gorochowski, TE (corresponding author), DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands.;Gorochowski, TE (corresponding author), Univ Bristol, BrisSynBio, Life Sci Bldg,Tyndall Ave, Bristol BS8 1TQ, Avon, England.
null
Aycilar-Kucukgoze, Irem;Bovenberg, Roel A L;Gorochowski, Thomas E;Ignatova, Zoya;Roubos, Johannes A
Biochemical Research Methods
European Commission [289384]; BrisSynBio; BBSRC/EPSRC Synthetic Biology Research Centre [BB/L01386X/1]; Biotechnology and Biological Sciences Research Council [BB/L01386X/1] Funding Source: researchfish; BBSRC [BB/L01386X/1] Funding Source: UKRI
WOS
Gorochowski, T E
DSM Biotechnol Ctr, Delft, Netherlands;Univ Bristol, Avon, England;Univ Groningen, Groningen, Netherlands;Univ Hamburg, Hamburg, Germany;Univ Potsdam, Potsdam, Germany
5
a;Allocation;and;between;Captures;dynamics;Endogenous;expression;genes;in;Minimal;model;of;Ribosome;synthetic;Trade-offs
3
Avcilar Kucukgoze, Irem;Gorochowski, Thomas;Ignatova, Zoya
AMER CHEMICAL SOC
DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands;DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands.; Gorochowski, TE (corresponding author), Univ Bristol, BrisSynBio, Life Sci Bldg,Tyndall Ave, Bristol BS8 1TQ, Avon, England;Univ Bristol, BrisSynBio, Life Sci Bldg,Tyndall Ave, Bristol BS8 1TQ, Avon, England;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Synthet Biol & Cell Engn, NL-9747 AG Groningen, Netherlands;Univ Hamburg, Dept Chem, Biochem & Mol Biol, D-20146 Hamburg, Germany;Univ Potsdam, Inst Biochem & Biol, Biochem, D-14476 Potsdam, Germany
Article
DSM Biotechnol Ctr;Univ Bristol
WASHINGTON
null
null
DSM Biotechnol Ctr;Univ Bristol;Univ Groningen;Univ Hamburg;Univ Potsdam
BBSRC;BBSRC/EPSRC Synthetic Biology Research Centre;Biotechnology and Biological Sciences Research Council;BrisSynBio;European Commission
Gorochowski, TE (corresponding author), DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands.; Gorochowski, TE (corresponding author), Univ Bristol, BrisSynBio, Life Sci Bldg,Tyndall Ave, Bristol BS8 1TQ, Avon, England.
720
Aycilar-Kucukgoze, Irem;Bovenberg, Roel A L;Gorochowski, Thomas E;Ignatova, Zoya;Roubos, Johannes A
18
5
380,183,000,020
BBSRC [BB/L01386X/1] Funding Source: UKRI;BBSRC/EPSRC Synthetic Biology Research Centre [BB/L01386X/1];Biotechnology and Biological Sciences Research Council [BB/L01386X/1] Funding Source: researchfish;BrisSynBio;European Commission [289384]
Germany;Netherlands;UK
ACS SYNTHETIC BIOLOGY
Netherlands;UK
null
null
DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands
2161-5063
Aycilar-Kucukgoze, I;Bovenberg, R A L;Gorochowski, T E;Ignatova, Z;Roubos, J A
JUL
thomas.gorochowski@bristol.ac.uk
expression;Minimal Model;Ribosome Allocation Dynamics Captures Trade-offs;Synthetic Genes
5
J
Biochemistry & Molecular Biology
additional ambient stress;burden;cell;cell physiology;cells;cellular growth;cellular resources;CIRCUITS;CODON USAGE;competition;CONSEQUENCES;considered;covering transcript abundance;demands;efficient heterologous expression;elongation time;ENDOGENOUS GENES;environmental stress;ESCHERICHIA-COLI;executing orthogonal genetic circuits;exposure;expression;finite set;genome;growth;guiding principles;host chassis;indirect interactions;intriguingly;largest proportion;maintenance;match experimental shifts;Minimal Model;model-predicted changes;optimization;parameters;places;processes;protein biosynthesis;protein synthesis resources;protein translation;PROTEIN-SYNTHESIS;redistribution;resource allocation;resources;responses;results;ribosome allocation;ribosome allocation dynamics;Ribosome Allocation Dynamics Captures Trade-offs;shared translational resources;simple model;SURVIVAL;synthetic;synthetic biology;synthetic circuits;Synthetic gene expression;synthetic genes;synthetic protein expression rate;systems biology;three key variables;tractable nature;transcript levels;translation;translation initiation rate;translation times;versatile tool
Gorochowski, T E
CIRCUITS;CODON USAGE;CONSEQUENCES;ESCHERICHIA-COLI;GENOME;GROWTH;OPTIMIZATION;protein biosynthesis;PROTEIN-SYNTHESIS;RESPONSES;Synthetic biology;systems biology;TRANSLATION
710
[Gorochowski, Thomas E.; Bovenberg, Roel A. L.; Roubos, Johannes A.] DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands. [Gorochowski, Thomas E.] Univ Bristol, BrisSynBio, Life Sci Bldg,Tyndall Ave, Bristol BS8 1TQ, Avon, England. [Aycilar-Kucukgoze, Irem; Ignatova, Zoya] Univ Potsdam, Inst Biochem & Biol, Biochem, D-14476 Potsdam, Germany. [Bovenberg, Roel A. L.] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Synthet Biol & Cell Engn, NL-9747 AG Groningen, Netherlands. [Ignatova, Zoya] Univ Hamburg, Dept Chem, Biochem & Mol Biol, D-20146 Hamburg, Germany.
All authors were supported by European Commission-funded Marie-Curie Actions Initial Training Network for Integrated Cellular Homeostasis (NICHE) Project 289384. T.E.G. was additionally supported by BrisSynBio, a BBSRC/EPSRC Synthetic Biology Research Centre (BB/L01386X/1).
additional ambient stress;burden;cell;cell physiology;cells;cellular growth;cellular resources;competition;considered;covering transcript abundance;demands;efficient heterologous expression;elongation time;endogenous genes;environmental stress;executing orthogonal genetic circuits;exposure;finite set;guiding principles;host chassis;indirect interactions;intriguingly;largest proportion;maintenance;match experimental shifts;minimal model;model-predicted changes;parameters;places;processes;protein synthesis resources;protein translation;redistribution;resource allocation;resources;results;ribosome allocation;ribosome allocation dynamics;shared translational resources;simple model;survival;synthetic;synthetic biology;synthetic circuits;synthetic gene expression;synthetic protein expression rate;three key variables;tractable nature;transcript levels;translation;translation initiation rate;translation times;versatile tool
10.1002/(SICI)1097-0290(19991020)65:2&lt;151::AID-BIT4&gt;3.0.CO;2-V;10.1006/jmbi.1993.1319;10.1007/978-88-470-0784-0_3];10.1007/s10955-011-0183-1;10.1016/0958-1669(95)80082-4;10.1016/j.bpj.2013.04.049;10.1016/j.bpj.2013.12.010;10.1016/j.bpj.2015.06.034;10.1016/j.cell.2014.02.033;10.1016/j.jmb.2008.06.068;10.1016/S0168-1656(00)00365-5;10.1016/S0958-1669(96)80051-6;10.1021/sb4001245;10.1038/msb.2011.94;10.1038/msb.2013.32;10.1038/nature08753;10.1038/nature10965;10.1038/nbt1172;10.1038/nrg2398;10.1038/nrg2899;10.1038/nrm1618;10.1073/pnas.0503858102;10.1073/pnas.0802190105;10.1073/pnas.1416533112;10.1093/bioinformatics/bts185;10.1093/gbe/evt174;10.1093/nar/gkt602;10.1093/nar/gkv1280;10.1093/nar/gkv199;10.1103/PhysRevLett.108.018102;10.1126/science.1170160;10.1126/science.1192588;10.1126/science.1241934;10.1128/JB.01990-07;10.1128/jb.177.6.1497-1504.1995;10.1128/JB.180.17.4704-4710.1998;10.1146/annurev.micro.61.080706.093440;10.1186/1475-2859-8-31;10.1371/journal.pcbi.1002127;10.1371/journal.pgen.1004392;10.1371/journal.pone.0127039;10.1385/MB:34:3:355;10.15252/msb.20145697;10.15252/msb.20156178;[10.1038/nmeth.2403, 10.1038/NMETH.2403];[10.1038/NMETH.2404, 10.1038/nmeth.2404];[10.1038/NMETH.2926, 10.1038/nmeth.2926];[10.1038/NMETH.3339, 10.1038/nmeth.3339]
DSM Biotechnol Ctr
Aycilar-Kucukgoze, I;Bovenberg, R A L;Gorochowski, T E;Ignatova, Z;Roubos, J A
Gorochowski, T E: DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands
Gorochowski, Thomas
289384;BB/L01386X/1
51
null
Netherlands
DSM Biotechnol Ctr;Univ Bristol;Univ Groningen;Univ Hamburg;Univ Potsdam
Gorochowski, Thomas E
Green Published, hybrid
CIRCUITS;CODON USAGE;CONSEQUENCES;ESCHERICHIA-COLI;GENOME;GROWTH;OPTIMIZATION;PROTEIN-SYNTHESIS;RESPONSES;TRANSLATION
Gorochowski, Thomas E.; Aycilar-Kucukgoze, Irem; Bovenberg, Roel A. L.; Roubos, Johannes A.; Ignatova, Zoya;
null
DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands;Univ Bristol, BrisSynBio, Life Sci Bldg,Tyndall Ave, Bristol BS8 1TQ, Avon, England;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Synthet Biol & Cell Engn, NL-9747 AG Groningen, Netherlands;Univ Hamburg, Dept Chem, Biochem & Mol Biol, D-20146 Hamburg, Germany;Univ Potsdam, Inst Biochem & Biol, Biochem, D-14476 Potsdam, Germany
DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands;Univ Bristol, BrisSynBio, Life Sci Bldg,Tyndall Ave, Bristol BS8 1TQ, Avon, England;Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Synthet Biol & Cell Engn, NL-9747 AG Groningen, Netherlands;Univ Hamburg, Dept Chem, Biochem & Mol Biol, D-20146 Hamburg, Germany;Univ Potsdam, Inst Biochem & Biol, Biochem, D-14476 Potsdam, Germany
null
protein biosynthesis;Synthetic biology;systems biology;translation
7
1925;1993;1995;1996;1998;1999;2001;2004;2005;2006;2007;2008;2009;2010;2011;2012;2013;2014;2015;2016
79
DSM Biotechnol Ctr, POB 1, NL-2600 MA Delft, Netherlands;Univ Bristol, BrisSynBio, Life Sci Bldg,Tyndall Ave, Bristol BS8 1TQ, Avon, England
ACS Synth. Biol.
Ignatova, Zoya
AMER CHEMICAL SOC
,;a;able;abundance;accurately;across;additional;after;allocation;also;ambient;among;and;arise;be;because;between;biology;burden;can;captures;capturing;cell;cells;cellular;changes;chassis;circuits;closely;competition;considered;construct;contain;contains;covering;critically;dedicated;demands;demonstrate;design;develop;distributed;dynamics;efficient;elongation;endogenous;ensure;environmental;executing;experimental;exploits;exploring;exposure;expressing;expression;faced;faithfully;finite;for;further;gene;genes;genetic;growth;guiding;here;heterologous;host;in;indirect;infer;initiation;interactions;intriguingly;is;it;key;largest;levels;maintenance;makes;many;match;minimal;model;model-predicted;must;nature;of;often;on;Orthogonal;our;parameters;physiology;places;principles;processes;proportion;protein;rarely;rate;redistribution;related;required;resource;resources;results;Ribosome;set;shared;shifts;show;simple;stress;survival;synthesis;synthetic;that;the;their;them;these;this;three;time;times;to;together;tool;tractable;transcript;translation;translational;variables;versatile;we;when;with;yet
DSM Biotechnol Ctr;Univ Bristol
Cells contain a finite set of resources that must be distributed across many processes to ensure survival. Among them, the largest proportion of cellular resources is dedicated to protein translation. Synthetic biology often exploits these resources in executing orthogonal genetic circuits, yet the burden this places on the cell is rarely considered. Here, we develop a minimal model of ribosome allocation dynamics capturing the demands on translation when expressing a synthetic construct together with endogenous genes required for the maintenance of cell physiology. Critically, it contains three key variables related to design parameters of the synthetic construct covering transcript abundance, translation initiation rate, and elongation time. We show that model-predicted changes in ribosome allocation closely match experimental shifts in synthetic protein expression rate and cellular growth. Intriguingly, the model is also able to accurately infer transcript levels and translation times after further exposure to additional ambient stress. Our results demonstrate that a simple model of resource allocation faithfully captures the redistribution of protein synthesis resources when faced with the burden of synthetic gene expression and environmental stress. The tractable nature of the model makes it a versatile tool for exploring the guiding principles of efficient heterologous expression and the indirect interactions that can arise between synthetic circuits and their host chassis because of competition for shared translational resources.
JPA-4825-2023
CIRCUITS;CODON USAGE;CONSEQUENCES;ESCHERICHIA-COLI;GENOME;GROWTH;OPTIMIZATION;PROTEIN-SYNTHESIS;RESPONSES;TRANSLATION
0
null
protein biosynthesis;Synthetic biology;systems biology;translation
11
ESCHERICHIA-COLI;CIRCUITS;CODON USAGE;CONSEQUENCES;GENOME;GROWTH;OPTIMIZATION;protein biosynthesis;PROTEIN-SYNTHESIS;RESPONSES;Synthetic biology;systems biology;TRANSLATION
WOS:000380183000020
DSM Biotechnol Ctr, Delft, Netherlands;Univ Bristol, Avon, England;Univ Groningen, Groningen, Netherlands;Univ Hamburg, Hamburg, Germany;Univ Potsdam, Potsdam, Germany
Germany;Netherlands;UK
2,016
null
0000-0002-9478-8825;0000-0003-1702-786X;0009-0006-7615-2969
null
null
English
null
ACS SYNTH BIOL;ANNU REV MICROBIOL;BIOINFORMATICS;BIOPHYS J;BIOTECHNOL BIOENG;CELL;CURR OPIN BIOTECH;ESCHERICHIA COLI SAL;GENOME BIOL EVOL;J BACTERIOL;J BIOTECHNOL;J MOL BIOL;J STAT PHYS;MICROB CELL FACT;MOL BIOTECHNOL;MOL SYST BIOL;NAT BIOTECHNOL;NAT METHODS;NAT REV GENET;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PHYS REV LETT;PHYSL STRESS RESPONS;PLOS COMPUT BIOL;PLOS GENET;PLOS ONE;SCIENCE;SCIENTIFICA ACTA;Z PHYS
Aycilar-Kucukgoze, Irem;Bovenberg, Roel A L;Gorochowski, Thomas E;Ignatova, Zoya;Roubos, Johannes A
2024-03-11 ER
[Anonymous];Basan, M;Bentele, K;Bratsun, D;Bremer H.;Brophy, J A N;Carbonell-Ballestero, M;Carpousis, A J;Ceroni, F;Chevance, F F V;Cookson, N A;Danino, T;Dong, H J;Enfors, S O;Farewell, A;Geertsma, E R;Goodman, D B;Gorochowski, T E;Gunasekera, T S;Gyorgy, A;Hess, A K;Holcik, M;Hui, S;Kane, J F;Kensy, F;Kudla, G;Lara, A R;Li, G W;Lsing E.;López-Maury, L;Marzuoli A.;Mather, W H;Mitarai, N;Mutalik, V K;Nuñez, P A;Plotkin, J B;Pédelacq, J D;Reuveni, S;Rondelez, Y;Schweder, T;Scott, M;Vind, J;Weickert, M J;Weisse, A Y;Wohlgemuth, S E;Zavala, E;Zia, R K P;Zur, H
DR8XZ
Avon, England;Delft, Netherlands.
90
null
5
null
27,112,032
Aycilar-Kucukgoze, Irem;Bovenberg, Roel A L;Gorochowski, Thomas E;Ignatova, Zoya;Roubos, Johannes A
ACS SYNTH BIOL
Avon, England;Delft, Netherlands;Groningen, Netherlands;Hamburg, Germany;Potsdam, Germany
Cleto, S;Jusiak, B;Lu, T K;Perez-Piñera, P
10.1016/j.tibtech.2015.12.014
null
84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
s5f3l3e3y4e354v633e5q3u6a6h675nu1s6s37
Engineering Synthetic Gene Circuits in Living Cells with CRISPR Technology
MIT
null
Lu, TK (corresponding author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.;Lu, TK (corresponding author), MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA.
null
Cleto, Sara;Jusiak, Barbara;Lu, Timothy K;Perez-Pinera, Pablo
Biotechnology & Applied Microbiology
null
WOS
Lu, T K
MIT, Cambridge, MA USA;Univ Illinois, Urbana, IL USA
34
Cells;circuits;CRISPR;engineering;gene;in;living;synthetic;technology;with
1
Cleto, Sara;Perez-Pinera, Pablo
ELSEVIER SCIENCE LONDON
MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA;Univ Illinois, Dept Bioengn, Urbana, IL USA
Review
MIT
LONDON
null
null
Elect Res Lab;MIT;Univ Illinois
null
Lu, TK (corresponding author), MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA.; Lu, TK (corresponding author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
547
Cleto, Sara;Jusiak, Barbara;Lu, Timothy K;Perez-Pinera, Pablo
88
3
378,961,700,006
null
USA
TRENDS IN BIOTECHNOLOGY
USA;USA.;
null
null
MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA
0167-7799
Cleto, S;Jusiak, B;Lu, T K;Perez-Piñera, P
JUL
tim@lugroup.org
CRISPR technology;engineering Synthetic Gene Circuits;living cells
4
J
Biotechnology & Applied Microbiology
ability;activation;basic research purposes;biomedical applications;CAS SYSTEMS;COMBINATORIAL GENETICS;control cell behavior;CRISPR;CRISPR technology;CRISPR-mediated gene regulation;designing synthetic TFs;effective synthetic transcription factors (TFs);efficient gene circuits;ENDOGENOUS GENES;engineering synthetic gene circuits;FINGER TRANSCRIPTION FACTORS;future;heterologous host cells;interspaced short palindromic repeat (CRISPR) system;living cells;logic gates;MAMMALIAN-CELLS;offers unprecedented ease;one;potential;programmable;prokaryotic;recent advances;REPRESSOR PROTEINS;RNA;sequence-specific;synthetic biology;synthetic gene circuits;TARGETING DNA;transcriptional regulation;transcriptional regulatory devices
Jusiak, B
ACTIVATION;CAS SYSTEMS;COMBINATORIAL GENETICS;ENDOGENOUS GENES;FINGER TRANSCRIPTION FACTORS;logic gates;MAMMALIAN-CELLS;REPRESSOR PROTEINS;RNA;TARGETING DNA
535
[Jusiak, Barbara; Cleto, Sara; Lu, Timothy K.] MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA. [Jusiak, Barbara; Cleto, Sara; Lu, Timothy K.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Perez-Pinera, Pablo] Univ Illinois, Dept Bioengn, Urbana, IL USA.
null
ability;basic research purposes;biomedical applications;control cell behavior;CRISPR;CRISPR-mediated gene regulation;designing synthetic TFs;effective synthetic transcription factors (TFs);efficient gene circuits;future;heterologous host cells;interspaced short palindromic repeat (CRISPR) system;offers unprecedented ease;one;potential;programmable;prokaryotic;recent advances;sequence-specific;synthetic biology;synthetic gene circuits;transcriptional regulation;transcriptional regulatory devices
10.1016/j.cbpa.2013.10.006;10.1016/j.cell.2007.05.045;10.1016/j.cell.2009.04.048;10.1016/j.cell.2012.05.045;10.1016/j.cell.2013.02.022;10.1016/j.cell.2013.06.044;10.1016/j.cell.2014.05.010;10.1016/j.cell.2014.09.029;10.1016/j.cell.2014.09.039;10.1016/j.cell.2014.11.052;10.1016/j.cels.2015.06.001;10.1016/j.chembiol.2014.12.011;10.1016/j.gene.2011.06.015;10.1016/j.molcel.2014.04.022;10.1016/j.pbi.2010.04.010;10.1016/j.stemcr.2013.07.002;10.1016/j.ymben.2011.10.003;10.1021/ja3065667;10.1021/sb400081r;10.1021/sb400114p;10.1038/35002131;10.1038/cr.2013.122;10.1038/gt.2008.96;10.1038/nature02491;10.1038/nature03461;10.1038/nature03556;10.1038/nature07389;10.1038/nature08753;10.1038/nature09886;10.1038/nature11149;10.1038/nature11516;10.1038/nature12148;10.1038/nature12466;10.1038/nature13769;10.1038/nature14136;10.1038/nbt.1536;10.1038/nbt.1755;10.1038/nbt.1775;10.1038/nbt.2351;10.1038/nbt.2508;10.1038/nbt.2510;10.1038/nbt.2623;10.1038/nbt.2673;10.1038/nbt.2675;10.1038/nbt.2842;10.1038/nbt.3011;10.1038/nbt.3199;10.1038/nbt.3326;10.1038/nbt0202-135;10.1038/nchembio.1753;10.1038/ncomms1516;10.1038/ncomms5408;10.1038/ncomms6393;10.1038/nrg2775;10.1038/nrm3738;10.1073/pnas.040552697;10.1073/pnas.1400093111;10.1073/pnas.91.10.4509;10.1073/pnas.94.11.5525;10.1074/jbc.M005108200;10.1093/emboj/cdg619;10.1093/nar/gks142;10.1093/nar/gkt135;10.1093/nar/gkt520;10.1093/nar/gku749;10.1099/mic.0.023960-0;10.1111/jipb.12152;10.1126/science.1138140;10.1126/science.1165771;10.1126/science.1172005;10.1126/science.1225829;10.1126/science.1232033;10.1126/science.1256272;10.1186/gb-2003-4-10-231;10.1371/journal.pone.0033279;10.15252/msb.20145735;10.1534/genetics.110.120717;10.4161/rna.23764;[10.1038/nmeth.2184, 10.1038/NMETH.2184];[10.1038/nmeth.2598, 10.1038/NMETH.2598];[10.1038/nmeth.2600, 10.1038/NMETH.2600];[10.1038/NMETH.2681, 10.1038/nmeth.2681];[10.1038/NMETH.2926, 10.1038/nmeth.2926];[10.1038/NMETH.2969, 10.1038/nmeth.2969];[10.1038/NMETH.3312, 10.1038/nmeth.3312];[10.1038/NMETH.3433, 10.1038/nmeth.3433];[10.1146/annurev.bioeng-071811-150118, 10.1146/annurev-bioeng-071811-150118]
MIT
Cleto, S;Jusiak, B;Lu, T K;Perez-Piñera, P
Jusiak, B: MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA
Lu, Timothy K
null
87
null
USA
MIT;Univ Illinois
Jusiak, Barbara
Bronze
ACTIVATION;CAS SYSTEMS;COMBINATORIAL GENETICS;ENDOGENOUS GENES;FINGER TRANSCRIPTION FACTORS;LOGIC GATES;MAMMALIAN-CELLS;REPRESSOR PROTEINS;RNA;TARGETING DNA
Jusiak, Barbara; Cleto, Sara; Perez-Pinera, Pablo; Lu, Timothy K.;
null
MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA;Univ Illinois, Dept Bioengn, Urbana, IL USA
MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA;Univ Illinois, Dept Bioengn, Urbana, IL USA
1879-3096
null
7
1994;1997;2000;2002;2003;2004;2005;2007;2008;2009;2010;2011;2012;2013;2014;2015
85
MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA;MIT, Elect Res Lab, Synthet Biol Ctr, Dept Biol Engn, Cambridge, MA 02139 USA
Trends Biotechnol.
Lu, Timothy K
ELSEVIER SCIENCE LONDON
(CRISPR);(TFs);,;ability;advances;and;applications;availability;basic;be;behavior;biology;biomedical;both;build;can;cell;cells;circuits;clustered;complex;control;CRISPR;CRISPR-mediated;depends;designing;devices;discuss;ease;effective;efficient;factors;for;future;gene;goals;harnessed;heterologous;host;how;in;increasingly;interspaced;is;of;offer;offers;on;one;palindromic;potential;programmable;prokaryotic;purposes;recent;recently;regularly;regulation;regulatory;repeat;research;review;sequence-specific;short;synthetic;system;TFs;that;the;to;transcription;transcriptional;unprecedented;used;various;we
MIT
One of the goals of synthetic biology is to build regulatory circuits that control cell behavior, for both basic research purposes and biomedical applications. The ability to build transcriptional regulatory devices depends on the availability of programmable, sequence-specific, and effective synthetic transcription factors (TFs). The prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR) system, recently harnessed for transcriptional regulation in various heterologous host cells, offers unprecedented ease in designing synthetic TFs. We review how CRISPR can be used to build synthetic gene circuits and discuss recent advances in CRISPR-mediated gene regulation that offer the potential to build increasingly complex, programmable, and efficient gene circuits in the future.
G-4267-2012
ACTIVATION;CAS SYSTEMS;COMBINATORIAL GENETICS;ENDOGENOUS GENES;FINGER TRANSCRIPTION FACTORS;LOGIC GATES;MAMMALIAN-CELLS;REPRESSOR PROTEINS;RNA;TARGET DNA
2
null
null
13
ACTIVATION;CAS SYSTEMS;COMBINATORIAL GENETICS;ENDOGENOUS GENES;FINGER TRANSCRIPTION FACTORS;logic gates;MAMMALIAN-CELLS;REPRESSOR PROTEINS;RNA;TARGET DNA
WOS:000378961700006
MIT, Cambridge, MA USA;Univ Illinois, Urbana, IL USA
USA
2,016
null
0000-0002-9167-0004;0000-0003-1273-0142
null
null
English
null
ACS SYNTH BIOL;ANNU REV BIOMED ENG;CELL;CELL RES;CELL SYST;CHEM BIOL;CURR OPIN CHEM BIOL;CURR OPIN PLANT BIOL;EMBO J;GENE;GENE THER;GENETICS;GENOME BIOL;J AM CHEM SOC;J BIOL CHEM;J INTEGR PLANT BIOL;METAB ENG;MICROBIOL-SGM;MOL CELL;MOL SYST BIOL;NAT BIOTECHNOL;NAT CHEM BIOL;NAT COMMUN;NAT METHODS;NAT REV GENET;NAT REV MOL CELL BIO;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS ONE;RNA BIOL;SCIENCE;STEM CELL REP
Cleto, Sara;Jusiak, Barbara;Lu, Timothy K;Perez-Pinera, Pablo
2024-03-11 ER
Ausländer, D;Ausländer, S;Bacchus, W;Barrangou, R;Basu, S;Beerli, R R;Bikard, D;Blount, B A;Bogdanove, A J;Boyle, P M;Brophy, J A N;Chavez, A;Cheng, A A;Cheng, A W;Christian, M;Citorik, R J;Daniel, R;Danino, T;Deans, T L;Deltcheva, E;Dicarlo, J E;Ellis, T;Esvelt, K M;Farzadfard, F;Friedland, A E;Fu, Y F;Gao, Y B;Gardner, T S;Gilbert, L A;Hilton, I B;Hsu, P D;Jiang, W Y;Jinek, M;Kabadi, A M;Khalil, A S;Kiani, S;Konermann, S;Lienert, F;Liu, C C;Liu, Q;Liu, Y C;Lohmueller, J J;Maeder, M L;Magnenat, L;Mali, P;Margolin, J F;Marraffini, L A;Mercer, A C;Miller, J C;Mimee, M;Mittler, G;Mojica, F J M;Moon, T S;Nielsen, A A;Nihongaki, Y;Nissim, L;O'Connell, M R;Orioli, A;Pattanayak, V;Perez-Pinera, P;Polstein, L R;Qi, L S;Sander, J D;Shah, S A;Shechner, D M;Siuti, P;Stricker, J;Tabor, J J;Tanenbaum, M E;Urnov, F D;Urrutia, R;Wang, B J;Wong, A S L;Ye, H F;You, L C;Zalatan, J G;Zhang, F;Zhang, Z H
DQ1LE
Cambridge, MA USA;Cambridge, MA USA.
109
null
2
null
26,809,780
Cleto, Sara;Jusiak, Barbara;Lu, Timothy K;Perez-Pinera, Pablo
TRENDS BIOTECHNOL
Cambridge, MA USA;Urbana, IL USA
Beuron, F;Herdewijn, P;Holliger, P;Morris, E P;Peak-Chew, S Y;Taylor, A I
10.1002/cbic.201600136
null
POSTFACH 101161, 69451 WEINHEIM, GERMANY
6g3s1o5v196c1w6t1ch59556r1s3m23315a6hs
Nanostructures from Synthetic Genetic Polymers
MRC
null
Taylor, AI (corresponding author), Concordia Univ, Dept Biol, Ctr Appl Synthet Biol, 7141 Rue Sherbrooke, Montreal, PQ H4B 1R6, Canada.;Taylor, AI; Holliger, P (corresponding author), MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.
null
Beuron, Fabienne;Herdewijn, Piet;Holliger, Philipp;Morris, Edward P;Peak-Chew, Sew-Yeu;Taylor, Alexander I
Biochemistry & Molecular Biology;Chemistry, Medicinal
Medical Research Council [U105178804]; European Science Foundation (ESF); Biotechnology and Biological Sciences Research Council [09-EuroSYNBIO-OP-013, INTENSIFY BB/M005623/1]; Cancer Research UK [C12209A16749]; MRC [MC_U105178804] Funding Source: UKRI; Cancer Research UK [16749] Funding Source: researchfish; Medical Research Council [MC_U105178804] Funding Source: researchfish
WOS
Holliger, P;Taylor, A I
Concordia Univ, Montreal PQ, Canada;Inst Canc Res, London, England;Katholieke Univ Leuven, Leuven, Belgium;MRC, Cambridge, England;Univ Evry, Evry, France
17
From;genetic;nanostructures;Polymers;synthetic
4
Herdewijn, Piet;Morris, Edward
WILEY-V C H VERLAG GMBH
Concordia Univ, Dept Biol, Ctr Appl Synthet Biol, 7141 Rue Sherbrooke, Montreal, PQ H4B 1R6, Canada;Inst Canc Res, Chester Beatty Labs, Div Struct Biol, 237 Fulham Rd, London SW3 6JB, England;Katholieke Univ Leuven, Rega Inst, Minderbroedersstr 10, B-3000 Leuven, Belgium;MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England;P (corresponding author), MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.; Taylor, AI (corresponding author), Concordia Univ, Dept Biol, Ctr Appl Synthet Biol, 7141 Rue Sherbrooke, Montreal, PQ H4B 1R6, Canada;Univ Evry, Inst Syst & Synthet Biol, 5 Rue Henri Desbrueres, F-91030 Evry, France
Article
Concordia Univ;MRC
WEINHEIM
null
null
Concordia Univ;Inst Canc Res;Katholieke Univ Leuven;Mol Biol Lab;MRC;Univ Evry
Biotechnology and Biological Sciences Research Council;Cancer Research UK;European Science Foundation (ESF);Medical Research Council;MRC
Taylor, AI; Holliger, P (corresponding author), MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.; Taylor, AI (corresponding author), Concordia Univ, Dept Biol, Ctr Appl Synthet Biol, 7141 Rue Sherbrooke, Montreal, PQ H4B 1R6, Canada.
1110
Beuron, Fabienne;Herdewijn, Piet;Holliger, Philipp;Morris, Edward P;Peak-Chew, Sew-Yeu;Taylor, Alexander I
51
5
379,156,400,009
Biotechnology and Biological Sciences Research Council [09-EuroSYNBIO-OP-013, INTENSIFY BB/M005623/1];Cancer Research UK [16749] Funding Source: researchfish;Cancer Research UK [C12209A16749];European Science Foundation (ESF);Medical Research Council [MC_U105178804] Funding Source: researchfish;Medical Research Council [U105178804];MRC [MC_U105178804] Funding Source: UKRI
Belgium;Canada;France;UK
CHEMBIOCHEM
Canada;UK
null
null
MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England
1439-4227
Beuron, F;Herdewijn, P;Holliger, P;Morris, E P;Peak-Chew, S Y;Taylor, A I
JUN 16
alex.taylor@concordia.ca;ph1@mrc-lmb.cam.ac.uk
nanostructures;Synthetic Genetic Polymers
6
J
Biochemistry & Molecular Biology;Pharmacology & Pharmacy
2-fluoroarabino nucleic acids (FANA);600kDa all-FANA octahedron;70kDa tetrahedra;alternative building blocks;assembly;CAGE;chemical biology;chemical scope;cyclohexene nucleic acids (CeNA);DELIVERY;DNA;DNA nanotechnology;electron microscopy;enhanced biostability;evolution;expanded range;four different XNA chemistries (2-fluro-2-deoxy-ribofuranose nucleic acid (2F-RNA);hexitol nucleic acids (HNA);implications;increasing complexity;materials;mixed designs;moderate chemical diversity;nano-objects;nanoscale objects;nanostructures;natural nucleic acids;nature;NUCLEIC-ACIDS;physicochemical properties;PNA;potential applications;programmable nanostructure assembly;results;RNA;scope;self-assembly;STRUCTURAL DNA NANOTECHNOLOGY;synthetic genetic polymers;SYSTEM;therapy;visualised;xeno nucleic acids (XNAs)
Taylor, A I
CAGE;chemical biology;DELIVERY;DNA nanotechnology;electron microscopy;EVOLUTION;NUCLEIC-ACIDS;PNA;RNA;self-assembly;STRUCTURAL DNA NANOTECHNOLOGY;SYSTEM;THERAPY;xeno nucleic acids (XNAs)
1107
[Taylor, Alexander I.; Peak-Chew, Sew-Yeu; Holliger, Philipp] MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England. [Taylor, Alexander I.] Concordia Univ, Dept Biol, Ctr Appl Synthet Biol, 7141 Rue Sherbrooke, Montreal, PQ H4B 1R6, Canada. [Beuron, Fabienne; Morris, Edward P.] Inst Canc Res, Chester Beatty Labs, Div Struct Biol, 237 Fulham Rd, London SW3 6JB, England. [Herdewijn, Piet] Katholieke Univ Leuven, Rega Inst, Minderbroedersstr 10, B-3000 Leuven, Belgium. [Herdewijn, Piet] Univ Evry, Inst Syst & Synthet Biol, 5 Rue Henri Desbrueres, F-91030 Evry, France.
This work was supported by the Medical Research Council (program no. U105178804 to P.H.) and by grants from the European Science Foundation (ESF) and the Biotechnology and Biological Sciences Research Council (09-EuroSYNBIO-OP-013 and INTENSIFY BB/M005623/1 to A.I.T.) and Cancer Research UK (C12209A16749 to E.P.M.) We would like to thank Christos Savva, Xiao-Chen Bai, and Sjores Scheres (MRC Laboratory of Molecular Biology) and Richard Berry (University of Oxford) for useful discussions and advice.
2-fluoroarabino nucleic acids (FANA);600kDa all-FANA octahedron;70kDa tetrahedra;alternative building blocks;assembly;chemical scope;cyclohexene nucleic acids (CeNA);DNA;electron microscopy;enhanced biostability;expanded range;four different XNA chemistries (2-fluro-2-deoxy-ribofuranose nucleic acid (2F-RNA);hexitol nucleic acids (HNA);implications;increasing complexity;materials;mixed designs;moderate chemical diversity;nano-objects;nanoscale objects;natural nucleic acids;nature;physicochemical properties;potential applications;programmable nanostructure assembly;results;RNA;scope;synthetic genetic polymers;visualised;xeno nucleic acids (XNAs)
10.1002/ANGE.200603392;10.1002/anie.200603392;10.1002/anie.201500561;10.1002/anie.201507375;10.1002/cbdv.200900185;10.1016/0022-5193(82)90002-9;10.1016/j.cbpa.2010.08.002;10.1016/j.cbpa.2014.09.022;10.1016/j.cell.2012.12.024;10.1016/j.cell.2014.03.008;10.1016/j.chembiol.2014.07.008;10.1021/ar500076k;10.1021/ja505101a;10.1021/nl304147f;10.1021/nl502385k;10.1021/nl901265n;10.1021/nn1024658;10.1021/nn2005574;10.1021/nn3022662;10.1021/nn503513p;10.1038/am.2013.22;10.1038/nature02307;10.1038/nature04586;10.1038/nature13982;10.1038/nsmb.2815;10.1039/b402293a;10.1039/b917661f;10.1039/c2cc36358e;10.1039/c2cc37556g;10.1073/pnas.1120964109;10.1088/0953-8984/24/16/164203;10.1093/nar/gkq1270;10.1093/nar/gks672;10.1093/nar/gkt808;10.1093/nar/gku617;10.1093/nar/gkv1057;10.1093/nar/gkv1472;10.1126/science.1104686;10.1126/science.1214081;10.1126/science.1217622;10.1126/science.1225624;10.1126/science.1227268;10.1126/science.1260901;10.1126/science.289.5481.920;10.3390/molecules200917645;10.4161/1949095X.2014.992181;[10.1038/NCHEM.1241, 10.1038/nchem.1241];[10.1038/nnano.2011.187, 10.1038/NNANO.2011.187];[10.1038/nnano.2014.100, 10.1038/NNANO.2014.100];[10.1038/nnano.2014.58, 10.1038/NNANO.2014.58];[10.1038/NNANO.2015.180, 10.1038/nnano.2015.180]
MRC
Beuron, F;Herdewijn, P;Holliger, P;Morris, E P;Peak-Chew, S Y;Taylor, A I
Taylor, A I: MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England
null
09-EuroSYNBIO-OP-013;16749;C12209A16749;INTENSIFY BB/M005623/1;MC_U105178804;U105178804
54
null
UK
Concordia Univ;Inst Canc Res;Katholieke Univ Leuven;MRC;Univ Evry
Taylor, Alexander I
Green Published, hybrid
CAGE;DELIVERY;EVOLUTION;NUCLEIC-ACIDS;PNA;RNA;STRUCTURAL DNA NANOTECHNOLOGY;SYSTEM;THERAPY
Taylor, Alexander I.; Beuron, Fabienne; Peak-Chew, Sew-Yeu; Morris, Edward P.; Herdewijn, Piet; Holliger, Philipp;
null
Concordia Univ, Dept Biol, Ctr Appl Synthet Biol, 7141 Rue Sherbrooke, Montreal, PQ H4B 1R6, Canada;Inst Canc Res, Chester Beatty Labs, Div Struct Biol, 237 Fulham Rd, London SW3 6JB, England;Katholieke Univ Leuven, Rega Inst, Minderbroedersstr 10, B-3000 Leuven, Belgium;MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England;Univ Evry, Inst Syst & Synthet Biol, 5 Rue Henri Desbrueres, F-91030 Evry, France
Concordia Univ, Dept Biol, Ctr Appl Synthet Biol, 7141 Rue Sherbrooke, Montreal, PQ H4B 1R6, Canada;Inst Canc Res, Chester Beatty Labs, Div Struct Biol, 237 Fulham Rd, London SW3 6JB, England;Katholieke Univ Leuven, Rega Inst, Minderbroedersstr 10, B-3000 Leuven, Belgium;MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England;Univ Evry, Inst Syst & Synthet Biol, 5 Rue Henri Desbrueres, F-91030 Evry, France
1439-7633
chemical biology;DNA nanotechnology;electron microscopy;self-assembly;xeno nucleic acids (XNAs)
12
1982;2000;2004;2006;2009;2010;2011;2012;2013;2014;2015;2016
42
Concordia Univ, Dept Biol, Ctr Appl Synthet Biol, 7141 Rue Sherbrooke, Montreal, PQ H4B 1R6, Canada;MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England
ChemBioChem
Holliger, Philipp
WILEY-V C H VERLAG GMBH
(2-fluro-2-deoxy-ribofuranose;(2F-RNA);(CeNA);(FANA);(HNA);(XNAs);,;2-fluoroarabino;600kDa;70kDa;:;a;acid;acids;all-FANA;also;alternative;an;and;applications;approximate;as;assembly;be;beyond;biostability;blocks;building;by;called;can;chemical;chemistries;complexity;constructed;construction;could;cyclohexene;describe;design;designs;different;diversity;DNA;elaborated;electron;enhanced;entirely;expanded;expanding;explore;extend;for;found;four;from;genetic;here;hexitol;however;implications;in;including;increasing;made;materials;microscopy;mixed;moderate;nano-objects;nanoscale;nanostructure;natural;nature;not;nucleic;objects;octahedron;of;or;our;physicochemical;polymers;potential;programmable;properties;range;results;RNA;scope;specifically;structural;synthetic;tetrahedra;the;to;visualised;we;well;with;xeno;XNA
Concordia Univ;MRC
Nanoscale objects of increasing complexity can be constructed from DNA or RNA. However, the scope of potential applications could be enhanced by expanding beyond the moderate chemical diversity of natural nucleic acids. Here, we explore the construction of nano-objects made entirely from alternative building blocks: synthetic genetic polymers not found in nature, also called xeno nucleic acids (XNAs). Specifically, we describe assembly of 70kDa tetrahedra elaborated in four different XNA chemistries (2-fluro-2-deoxy-ribofuranose nucleic acid (2F-RNA), 2-fluoroarabino nucleic acids (FANA), hexitol nucleic acids (HNA), and cyclohexene nucleic acids (CeNA)), as well as mixed designs, and a approximate to 600kDa all-FANA octahedron, visualised by electron microscopy. Our results extend the chemical scope for programmable nanostructure assembly, with implications for the design of nano-objects and materials with an expanded range of structural and physicochemical properties, including enhanced biostability.
null
CAGES;DELIVERY;EVOLUTION;NUCLEIC-ACIDS;PNA;RNA;STRUCTURAL DNA NANOTECHNOLOGY;SYSTEM;THERAPY
2
null
chemical biology;DNA nanotechnology;electron microscopy;self-assembly;xeno nucleic acids (XNAs)
4
CAGES;chemical biology;DELIVERY;DNA nanotechnology;ELECTRON-MICROSCOPY;EVOLUTION;NUCLEIC-ACIDS;PNA;RNA;self-assembly;STRUCTURAL DNA NANOTECHNOLOGY;SYSTEM;THERAPY;xeno nucleic acids (XNAs)
WOS:000379156400009
Concordia Univ, Montreal PQ, Canada;Inst Canc Res, London, England;Katholieke Univ Leuven, Leuven, Belgium;MRC, Cambridge, England;Univ Evry, Evry, France
Belgium;Canada;France;UK
2,016
null
0000-0003-3544-0041;0000-0003-3589-8503
null
null
English
null
ACCOUNTS CHEM RES;ACS NANO;ANGEW CHEM;ANGEW CHEM INT EDIT;Artif DNA PNA XNA;CELL;CHEM BIODIVERS;CHEM BIOL;CHEM COMMUN;CURR OPIN CHEM BIOL;J AM CHEM SOC;J PHYS-CONDENS MAT;J THEOR BIOL;MOLECULES;NANO LETT;NAT CHEM;NAT NANOTECHNOL;NAT STRUCT MOL BIOL;NATURE;NPG ASIA MATER;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;SCIENCE
Beuron, Fabienne;Herdewijn, Piet;Holliger, Philipp;Morris, Edward P;Peak-Chew, Sew-Yeu;Taylor, Alexander I
2024-03-11 ER
Afonin, K A;Amir, Y;Anosova, I;Breaker, R R;Burns, J R;Cassinelli, V;Cech, T R;Chworos, A;Conway, J W;Cozens, C;Douglas, S M;Erben C.M.;Erben, C M;Ferreira-Bravo, I A;Fica, S M;Flory Justin, D;Fu, J L;Goodman, R P;Grabow, W W;Hahn, J;Herdewijn, P;Jones, M R;Kato, T;Ke, Y G;Keum, J W;Langecker, M;Liu, J;Lo, P K;Martín-Pintado, N;Nissen, P;Pallan, P S;Pedersen, R O;Pei, H;Peters, J P;Pinheiro, A V;Pinheiro, V B;Rothemund, P W K;Sachdeva, G;Seeman, N C;Serganov, A;Shih, W M;Stern, A;Surana, S;Taylor, A I;Walsh, A S;Wilds C. J.;Yamazaki, T;Yu, H Y;Zhang, F;Zhao, Y X;Zuo H.;Zuo, H
DQ4EJ
Cambridge, England.;Montreal PQ, Canada
46
null
5
null
26,992,063
Beuron, Fabienne;Herdewijn, Piet;Holliger, Philipp;Morris, Edward P;Peak-Chew, Sew-Yeu;Taylor, Alexander I
CHEMBIOCHEM
Cambridge, England;Evry, France;Leuven, Belgium;London, England;Montreal PQ, Canada
Ang, K S;Kyriakopoulos, S;Lee, D Y;Li, W
10.1016/j.ymeth.2016.01.016
null
525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
4h4h5t49t2h1k5g651ja6x3g2y5h54m1b2z1w
Multi-omics data driven analysis establishes reference codon biases for synthetic gene design in microbial and mammalian cells
Natl Univ Singapore
null
Lee, DY (corresponding author), Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore.
null
Ang, Kok Siong;Kyriakopoulos, Sarantos;Lee, Dong-Yup;Li, Wei
Biochemical Research Methods;Biochemistry & Molecular Biology
National University of Singapore; National Research Foundation of Singapore [NRF2013-THE001-035]; Biomedical Research Council of A*STAR (Agency for Science, Technology and Research), Singapore; Next-Generation BioGreen 21 Program (SSAC), Rural Development Administration, Republic of Korea [PJ01109405]
WOS
Lee, D Y
ASTAR, Singapore, Singapore;Natl Univ Singapore, Singapore, Singapore;Sangon Biotech Shanghai Co Ltd, Shanghai, Peoples R China
102
Analysis;and;biases;Cells;codon;data;design;driven;establishes;for;gene;in;mammalian;microbial;multi-omics;reference;synthetic
2
Lee, Dong-Yup
ACADEMIC PRESS INC ELSEVIER SCIENCE
ASTAR, Bioproc Technol Inst, 20 Biopolis Way,06-01 Ctr, Singapore 138668, Singapore;Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore;Natl Univ Singapore, Inst Life Sci, NUS Synthet Biol Clin & Technol Innovat SynCTI, 28 Med Dr, Singapore 117456, Singapore;Sangon Biotech Shanghai Co Ltd, 698 Xiangmin Rd, Shanghai 201611, Peoples R China
Article
Natl Univ Singapore
SAN DIEGO
null
null
ASTAR;Natl Univ Singapore;Sangon Biotech Shanghai Co Ltd
Biomedical Research Council of A*STAR (Agency for Science, Technology and Research), Singapore;National Research Foundation of Singapore;National University of Singapore;Next-Generation BioGreen 21 Program (SSAC), Rural Development Administration, Republic of Korea
Lee, DY (corresponding author), Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore.
35
Ang, Kok Siong;Kyriakopoulos, Sarantos;Lee, Dong-Yup;Li, Wei
10
4
377,316,200,005
Biomedical Research Council of A*STAR (Agency for Science, Technology and Research), Singapore;National Research Foundation of Singapore [NRF2013-THE001-035];National University of Singapore;Next-Generation BioGreen 21 Program (SSAC), Rural Development Administration, Republic of Korea [PJ01109405]
China;Singapore
METHODS
Singapore
null
null
Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore
1046-2023
Ang, K S;Kyriakopoulos, S;Lee, D Y;Li, W
JUN 1
cheld@nus.edu.sg
mammalian cells;multi-omics data driven analysis;reference codon biases;synthetic gene design
4
J
Biochemistry & Molecular Biology
-omics specific codon biases;-omics subsets;abundant proteins;analyzed multi-omics data;available genomic;C 2016 Elsevier Inc;CARBON-SOURCES;CC;Chinese hamster ovary (CHO) cells;CHO cells;codon;codon bias patterns;codon context (CC);Codon optimization;codon pair frequencies;correlation;different input codon biases;effect;ENHANCED EXPRESSION;Escherichia coli;ESCHERICHIA-COLI;expressed transcripts;expression;general lack;genome sequence;HAMSTER OVARY CELLS;HIGH-LEVEL EXPRESSION;host dependent;human IFN gamma sequence;ICU;improved heterologous gene design;individual codon;individual codon usage (ICU) design parameters;mammalian cells;mammalian expression hosts;Microbial and mammalian hosts;microbial cells;mRNA;Multi-omics data;multi-omics data driven analysis;one cluster;Pichia pastoris;PICHIA-PASTORIS;principal component analysis;protein expression levels;proteomic;PROTEOMIC ANALYSIS;RECOMBINANT PROTEIN-PRODUCTION;Reference codon bias;reference codon biases;reference codon usage biases;results;rights reserved;robust design parameter;Saccharomyces cerevisiae;SACCHAROMYCES-CEREVISIAE;SEQUENCES;silico case study;similar codon bias patterns;study;subsets;Synthetic gene design;transcriptomic;translatomic data;via
Ang, K S
CARBON-SOURCES;Codon optimization;ENHANCED EXPRESSION;ESCHERICHIA-COLI;GENOME SEQUENCE;HAMSTER OVARY CELLS;HIGH-LEVEL EXPRESSION;Microbial and mammalian hosts;Multi-omics data;PICHIA-PASTORIS;PROTEOMIC ANALYSIS;RECOMBINANT PROTEIN-PRODUCTION;Reference codon bias;SACCHAROMYCES-CEREVISIAE;Synthetic gene design
26
[Ang, Kok Siong; Lee, Dong-Yup] Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore. [Ang, Kok Siong; Lee, Dong-Yup] Natl Univ Singapore, Inst Life Sci, NUS Synthet Biol Clin & Technol Innovat SynCTI, 28 Med Dr, Singapore 117456, Singapore. [Kyriakopoulos, Sarantos; Lee, Dong-Yup] ASTAR, Bioproc Technol Inst, 20 Biopolis Way,06-01 Ctr, Singapore 138668, Singapore. [Li, Wei] Sangon Biotech Shanghai Co Ltd, 698 Xiangmin Rd, Shanghai 201611, Peoples R China.
This work was supported by the National University of Singapore, the National Research Foundation of Singapore (NRF2013-THE001-035), Biomedical Research Council of A*STAR (Agency for Science, Technology and Research), Singapore, and a grant from the Next-Generation BioGreen 21 Program (SSAC, No. PJ01109405), Rural Development Administration, Republic of Korea.
-omics specific codon biases;-omics subsets;abundant proteins;analyzed multi-omics data;available genomic;CC;Chinese hamster ovary (CHO) cells;CHO cells;codon;codon bias patterns;codon context (CC);codon optimization;codon pair frequencies;correlation;different input codon biases;effect;Escherichia coli;expressed transcripts;expression;general lack;host dependent;human IFN gamma sequence;ICU;improved heterologous gene design;individual codon;individual codon usage (ICU) design parameters;mammalian expression hosts;microbial cells;mRNA;one cluster;Pichia pastoris;principal component analysis;protein expression levels;proteomic;reference codon usage biases;results;robust design parameter;Saccharomyces cerevisiae;sequences;silico case study;similar codon bias patterns;study;subsets;synthetic gene design;transcriptomic;translatomic data;via
10.1002/pmic.201400267;10.1007/s00253-012-4540-z;10.1007/s00253-014-6079-7;10.1007/s00449-014-1333-z;10.1007/s10295-013-1341-z;10.1007/s10529-012-1097-y;10.1007/s11693-010-9062-3;10.1016/j.cell.2014.02.033;10.1016/j.ejps.2012.11.016;10.1016/j.enzmictec.2015.04.008;10.1016/j.febslet.2009.10.036;10.1016/j.jbiotec.2013.07.010;10.1016/j.jbiotec.2013.07.011;10.1016/j.jtbi.2013.11.022;10.1016/j.molcel.2015.05.035;10.1016/j.pep.2013.12.006;10.1021/pr300476w;10.1038/nature02046;10.1038/nbt.1544;10.1038/nbt.1932;10.1073/pnas.1120799109;10.1074/mcp.M113.029165;10.1093/bioinformatics/btl117;10.1093/nar/gkj405;10.1098/rsif.2008.0520.focus;10.1128/JB.00034-09;10.1134/S0003683814090051;10.1186/1471-2164-13-738;10.1186/1475-2859-10-15;10.1186/1752-0509-6-134;10.1186/1752-0509-8-33;10.1186/s12864-015-1393-8;10.1186/s12896-015-0177-1;10.1371/journal.pgen.1004734;10.1371/journal.pone.0123288;10.1534/g3.113.008995
Natl Univ Singapore
Ang, K S;Kyriakopoulos, S;Lee, D Y;Li, W
Ang, K S: Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore
Ang, Kok Siong;Lee, Dong-Yup
NRF2013-THE001-035;PJ01109405
36
null
Singapore
ASTAR;Natl Univ Singapore;Sangon Biotech Shanghai Co Ltd
Ang, Kok Siong
null
CARBON-SOURCES;ENHANCED EXPRESSION;ESCHERICHIA-COLI;GENOME SEQUENCE;HAMSTER OVARY CELLS;HIGH-LEVEL EXPRESSION;PICHIA-PASTORIS;PROTEOMIC ANALYSIS;RECOMBINANT PROTEIN-PRODUCTION;SACCHAROMYCES-CEREVISIAE
Ang, Kok Siong; Kyriakopoulos, Sarantos; Li, Wei; Lee, Dong-Yup;
null
ASTAR, Bioproc Technol Inst, 20 Biopolis Way,06-01 Ctr, Singapore 138668, Singapore;Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore;Natl Univ Singapore, Inst Life Sci, NUS Synthet Biol Clin & Technol Innovat SynCTI, 28 Med Dr, Singapore 117456, Singapore;Sangon Biotech Shanghai Co Ltd, 698 Xiangmin Rd, Shanghai 201611, Peoples R China
ASTAR, Bioproc Technol Inst, 20 Biopolis Way,06-01 Ctr, Singapore 138668, Singapore;Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore;Natl Univ Singapore, Inst Life Sci, NUS Synthet Biol Clin & Technol Innovat SynCTI, 28 Med Dr, Singapore 117456, Singapore;Sangon Biotech Shanghai Co Ltd, 698 Xiangmin Rd, Shanghai 201611, Peoples R China
1095-9130
Codon optimization;Microbial and mammalian hosts;Multi-omics data;Reference codon bias;Synthetic gene design
null
2003;2006;2009;2010;2011;2012;2013;2014;2015
16
Natl Univ Singapore, Dept Chem & Biomol Engn, 4 Engn Dr 4, Singapore 117585, Singapore
Methods
Lee, Dong-Yup
ACADEMIC PRESS INC ELSEVIER SCIENCE
(CC);(CHO);(ICU);,;-omics;abundant;among;analysis;analyzed;and;are;available;between;bias;biases;by;case;CC;cells;cerevisiae;Chinese;CHO;cluster;clustering;codon;coli;compared;compiled;component;context;correlation;data;dependent;derive;design;despite;different;distinguishable;effect;efficiently;Escherichia;establish;expressed;expression;for;forming;frequencies;further;gamma;gene;general;generated;genomic;hamster;heterologous;hierarchical;highly;host;hosts;however;human;ICU;IFN;improved;in;indicated;individual;input;interestingly;investigated;is;lack;levels;mammalian;microbial;more;mRNA;multi-omics;not;of;on;one;optimization;optimized;our;ovary;pair;parameter;parameters;pastoris;patterns;Pichia;principal;protein;proteins;proteomic;publicly;reference;results;robust;Saccharomyces;sequence;sequences;silico;similar;specific;specifically;study;subsets;supported;synthetic;than;that;the;their;then;thereof;this;thus;to;transcriptomic;transcripts;translated;translatomic;usage;using;various;via;we;were
Natl Univ Singapore
In this study, we analyzed multi-omics data and subsets thereof to establish reference codon usage biases for codon optimization in synthetic gene design. Specifically, publicly available genomic, transcriptomic, proteomic and translatomic data for microbial and mammalian expression hosts, Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris and Chinese hamster ovary (CHO) cells, were compiled to derive their individual codon and codon pair frequencies. Then, host dependent and -omics specific codon biases were generated and compared by principal component analysis and hierarchical clustering. Interestingly, our results indicated the similar codon bias patterns of the highly expressed transcripts, highly abundant proteins, and efficiently translated mRNA in microbial cells, despite the general lack of correlation between mRNA and protein expression levels. However, for CHO cells, the codon bias patterns among various -omics subsets are not distinguishable, forming one cluster. Thus, we further investigated the effect of different input codon biases on codon optimized sequences using the codon context (CC) and individual codon usage (ICU) design parameters, via in silico case study on the expression of human IFN gamma sequence in CHO cells. The results supported that CC is more robust design parameter than ICU for improved heterologous gene design.
D-6650-2011;M-2674-2019
CARBON-SOURCES;ENHANCED EXPRESSION;ESCHERICHIA-COLI;GENOME SEQUENCE;HAMSTER OVARY CELLS;HIGH-LEVEL EXPRESSION;PICHIA-PASTORIS;PROTEOMIC ANALYSIS;RECOMBINANT PROTEIN-PRODUCTION;SACCHAROMYCES-CEREVISIAE
0
null
Codon optimization;Microbial and mammalian hosts;Multi-omics data;Reference codon bias;Synthetic gene design
10
ESCHERICHIA-COLI;SACCHAROMYCES-CEREVISIAE;CARBON-SOURCES;Codon optimization;ENHANCED EXPRESSION;GENOME SEQUENCE;HAMSTER OVARY CELLS;HIGH-LEVEL EXPRESSION;Microbial and mammalian hosts;Multi-omics data;Pichia pastoris;PROTEOMIC ANALYSIS;RECOMBINANT PROTEIN-PRODUCTION;Reference codon bias;Synthetic gene design
WOS:000377316200005
ASTAR, Singapore, Singapore;Natl Univ Singapore, Singapore, Singapore;Sangon Biotech Shanghai Co Ltd, Shanghai, Peoples R China
China;Singapore
2,016
null
0000-0003-0901-708X
null
null
English
null
APPL BIOCHEM MICRO+;APPL MICROBIOL BIOT;BIOINFORMATICS;BIOPROC BIOSYST ENG;BIOTECHNOL LETT;BMC BIOTECHNOL;BMC GENOMICS;BMC SYST BIOL;CELL;ENZYME MICROB TECH;EUR J PHARM SCI;FEBS LETT;J BACTERIOL;J BIOTECHNOL;J IND MICROBIOL BIOT;J PROTEOME RES;J R SOC INTERFACE;J THEOR BIOL;MICROB CELL FACT;MOL CELL;MOL CELL PROTEOMICS;NAT BIOTECHNOL;NATURE;NUCLEIC ACIDS RES;P NATL ACAD SCI USA;PLOS GENET;PLOS ONE;PROTEIN EXPRES PURIF;PROTEOMICS;Syst Synth Biol
Ang, Kok Siong;Kyriakopoulos, Sarantos;Lee, Dong-Yup;Li, Wei
2024-03-11 ER
Adhikari, H;Ata Ö;Baycin-Hizal, D;Bin Pek, H;Chung, B K S;Courtes, F C;De Schutter, K;Engel, S R;Gerashchenko, M V;Ghaemmaghami, S;He, M;Kim, H J;Krug, K;Lanza, A M;Lewis, N E;Li, G W;Liang, S L;Liu, G L;Liu, X W;Lu, X M;Maier, T;Menzella, H G;Prielhofer, R;Quax, T E F;Raab David;Renuse, S;Riley, M;Sarantos, K;Shukurov, R R;Snajder, M;Suzuki, R;Tu, Y B;Wei, W;Welch, M;Xu, X
DN8GC
Singapore, Singapore
16
null
3
null
26,850,284
Ang, Kok Siong;Kyriakopoulos, Sarantos;Lee, Dong-Yup;Li, Wei
METHODS
Shanghai, Peoples R China;Singapore, Singapore
Glyzin, S D;Kolesov, A Y;Rozov, N K
10.1134/S0040577916060106
null
233 SPRING ST, NEW YORK, NY 10013-1578 USA
255f1172432t13f5i6z252u3h10j4x5j126r3h
BUFFERING IN CYCLIC GENE NETWORKS
Demidov Yaroslavl State Univ
null
Glyzin, SD (corresponding author), Demidov Yaroslavl State Univ, Yaroslavl, Russia.
null
Glyzin, S D;Kolesov, A Yu;Rozov, N Kh
Physics, Mathematical;Physics, Multidisciplinary
Russian Foundation for Basic Research [15-01-04066_a]; Russian State Research Task [2014/258, 1875]
WOS
Glyzin, S D
Demidov Yaroslavl State Univ, Yaroslavl, Russia;Lomonosov Moscow State Univ, Moscow, Russia
187
BUFFERING;CYCLIC;gene;in;networks
1
Glyzin, Sergey;Rozov, Nicolai;Rozov, Nikolai
MAIK NAUKA/INTERPERIODICA/SPRINGER
Demidov Yaroslavl State Univ, Yaroslavl, Russia;Lomonosov Moscow State Univ, Moscow, Russia
Article
Demidov Yaroslavl State Univ
NEW YORK
null
null
Demidov Yaroslavl State Univ;Lomonosov Moscow State Univ
Russian Foundation for Basic Research;Russian State Research Task
Glyzin, SD (corresponding author), Demidov Yaroslavl State Univ, Yaroslavl, Russia.
951
Glyzin, S D;Kolesov, A Yu;Rozov, N Kh
3
2
379,309,300,010
Russian Foundation for Basic Research [15-01-04066_a];Russian State Research Task [2014/258, 1875]
Russia
THEORETICAL AND MATHEMATICAL PHYSICS
Russia
null
null
Demidov Yaroslavl State Univ, Yaroslavl, Russia
0040-5779
Glyzin, S D;Kolesov, A Y;Rozov, N K
JUN
fpo.mgu@mail.ru;glyzin@uniyar.ac.ru;kolesov@uniyar.ac.ru
BUFFERING;CYCLIC GENE NETWORKS
3
J
Physics
appropriate choice;artificial gene network;artificial oscillating gene networks;asymptotic behavior;buffering;CHAINS;cyclic chain of unidirectionally coupled equations;cyclic chains;CYCLIC GENE NETWORKS;given finite number;mathematical models;parameters;phenomenon;RELAXATION SELF-OSCILLATIONS;so-called traveling waves;special type;stability;stable periodic motions;SYSTEM;traveling wave;unidirectionally coupled delay differential-difference equations
Glyzin, S D
artificial gene network;asymptotic behavior;buffering;CHAINS;cyclic chain of unidirectionally coupled equations;RELAXATION SELF-OSCILLATIONS;STABILITY;traveling wave
935
[Glyzin, S. D.; Kolesov, A. Yu.] Demidov Yaroslavl State Univ, Yaroslavl, Russia. [Rozov, N. Kh.] Lomonosov Moscow State Univ, Moscow, Russia.
This research was supported by the Russian Foundation for Basic Research (Grant No. 15-01-04066_a) and the Russian State Research Task No. 2014/258 (Project No. 1875).
appropriate choice;artificial oscillating gene networks;cyclic chains;given finite number;mathematical models;parameters;phenomenon;so-called traveling waves;special type;stable periodic motions;system;unidirectionally coupled delay differential-difference equations
10.1007/s11232-013-0041-1;10.1038/35002125;10.1070/IM2013v077n02ABEH002636;10.1070/IM2014v078n04ABEH002704;10.1103/PhysRevE.81.066206;10.1134/S0012266111070020;10.1134/S0012266113100017;10.1134/S0965542510120031;10.1142/S0218127409025237
Demidov Yaroslavl State Univ
Glyzin, S D;Kolesov, A Y;Rozov, N K
Glyzin, S D: Demidov Yaroslavl State Univ, Yaroslavl, Russia
Glyzin, Sergey;Kolesov, Andrei Yu.;Kolesov, Andrey;Rozov, Nicolai
15-01-04066_a;1875;2014/258
15
null
Russia
Demidov Yaroslavl State Univ;Lomonosov Moscow State Univ
Glyzin, S D
null
CHAINS;RELAXATION SELF-OSCILLATIONS
Glyzin, S. D.; Kolesov, A. Yu.; Rozov, N. Kh.;
null
Demidov Yaroslavl State Univ, Yaroslavl, Russia;Lomonosov Moscow State Univ, Moscow, Russia
Demidov Yaroslavl State Univ, Yaroslavl, Russia;Lomonosov Moscow State Univ, Moscow, Russia
1573-9333
artificial gene network;asymptotic behavior;buffering;cyclic chain of unidirectionally coupled equations;stability;traveling wave
3
1952;1997;2000;2003;2004;2009;2010;2011;2013;2014
4
Demidov Yaroslavl State Univ, Yaroslavl, Russia
Theor. Math. Phys.
Rozov, N Kh
MAIK NAUKA/INTERPERIODICA/SPRINGER
,;:;a;an;any;appropriate;are;artificial;buffering;chains;choice;coexist;consider;coupled;cyclic;delay;differential-difference;equations;establish;finite;for;gene;given;in;is;mathematical;models;motions;networks;number;of;oscillating;parameters;periodic;phenomenon;realized;so-called;special;stable;system;that;the;these;traveling;type;unidirectionally;waves;we
Demidov Yaroslavl State Univ
We consider cyclic chains of unidirectionally coupled delay differential-difference equations that are mathematical models of artificial oscillating gene networks. We establish that the buffering phenomenon is realized in these system for an appropriate choice of the parameters: any given finite number of stable periodic motions of a special type, the so-called traveling waves, coexist.
A-7646-2018;AAU-2535-2020;ABC-6838-2021;B-2224-2013
CHAIN;RELAXATION SELF-OSCILLATIONS
0
null
artificial gene network;asymptotic behavior;buffering;cyclic chain of unidirectionally coupled equations;stability;traveling wave
17
artificial gene network;asymptotic behavior;buffering;CHAIN;cyclic chain of unidirectionally coupled equations;RELAXATION SELF-OSCILLATIONS;STABILITY;traveling waves
WOS:000379309300010
Demidov Yaroslavl State Univ, Yaroslavl, Russia;Lomonosov Moscow State Univ, Moscow, Russia
Russia
2,016
null
0000-0001-8585-298X;0000-0002-6403-4061;0000-0002-9330-549X
null
null
English
null
COMP MATH MATH PHYS;COMP MATH MATH PHYS+;DIFF EQUAT+;INT J BIFURCAT CHAOS;IZV MATH+;NATURE;P STEKLOV I MATH;PHYS REV E;SIB ZH IND MAT;THEOR MATH PHYS+
Glyzin, S D;Kolesov, A Yu;Rozov, N Kh
2024-03-11 ER
Buse, O;Demidenko G.V.;Elowitz, M B;Fadeev, S I;Glyzin, S D;Kolesov A. Yu.;Kolesov, A Y;Likhoshvai V.A.;Tikhonov Andreinikolaevich;Volokitin, E P
DQ6IY
Yaroslavl, Russia
4
null
2
null
null
Glyzin, S D;Kolesov, A Yu;Rozov, N Kh
THEOR MATH PHYS+
Moscow, Russia;Yaroslavl, Russia