大学共同利用機関法人 自然科学研究機構
生命創成探究センター

Inter-University Research Institute Corporation
National Instutetes of Natural Sciences

Exploratory Research Center
on Life and Living Systems

Message from the Director
KATO, Koichi Ph.D.

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What is life? The Exploratory Research Center on Life and Living Systems (ExCELLS) wasestablished in April 2018 to address this fundamental question. The essence of living systems
has long been explored by physicists, including Erwin Schrödinger and Ilya Prigogine, and has
been characterized as open systems in disequilibrium. Omics-based approaches that havebeen developed in recent decades have provided comprehensive knowledge on biomolecules
as parts of living systems. However, the fundamental question of how these biomolecules areintegrated into living systems remains unanswered. ExCELLS aims to achieve a comprehensive
understanding of living systems beyond reductionism by utilizing large-scale data analyses andsynthetic biology approaches. For this purpose, ExCELLS develops novel approaches forobserving biological entities, deciphering hidden information, and creating living systems to
improve understanding of their nature. Moreover, ExCELLS promotes collaborative,
interdisciplinary research involving investigators who explore organisms living in extreme
environments and provides a unique platform for cross-disciplinary research in aninteruniversity, collaborative environment, using the “Observe, Read, and Create” approach.
Furthermore, for developing a strong research and innovation base, ExCELLS enlightens young
people to become the next generation scientists. To achieve our aims, we would like to expand
our international collaborative network. Therefore, your cooperation would be greatly
appreciated!

Observe

Read
1

Exploration ofLife in Extreme
Environments

CreateOrganizaion

NINS
National Institutes of
Natural Sciences

National Astronomical Observatory of Japan

National Institute for Fusion Science

National Instutute for Basic Biology

National Institute for Physiological Science

President

Institute for Molecular Science

Center for Novel Science Intiatives

Astrobiology Center
Exploratory Research Center
on Life and Living Systems

ExCELLS
Exploratory ResearchCenter on Life andLiving Systems

Department of Creative Research
Bioimage Informatics Group
Biomolecular Dynamics Simulation Group
Biomolecular Organization Research Group
Cardiocirculatory Dynamism Research Group
Cognitive Genomics Research Group
Developmental Signaling Research Group
Dynamic Molecular Neurobiology Group
Metallobiology Group
Neuronal Networks Research Group
Protein Design Group
Cognitive Genomics Research Group
Quantitative Biology Group

Director

Spatiotemporal Regulations Group
Thermal Biology Group
Plant Development and Physiology Research Group
Biofunctional Systems Construction Research Group
Constructive Biology Group
Nuclear Dynamics Group

Collaborative Research Group
Biomolecular Dynamics Observation Group
Collaborative Research Coordinator

Section for Exploration of Lifein Extreme Environments
Deep-Sea and Deep Subsurface Life Research Group
Extreme Environmental Biomolecular Research Group2

Department of Creative Research
Bioimage Informatics GroupTAKADA, Shinji / KATO, Kagayaki / OHTA, Yusaku
Modern microscopic techniques used in the biological ﬁeld yield large amounts ofimaging data that generally include multiple dimensions, such as depth and temporalaxes. Thus, they can be diﬃcult to interpret with the naked eye. In addition, thesebiological specimens take various shapes and are often changing.
To overcome this and extract biological descriptions from them, we are developing
specialized algorithms for extracting image features out of multi-dimensional
biological images. We will also apply these to processing large amounts of imaging
data for further analysis by building an image processing pipeline.

References：
・Nishimura R, Kato K, Fujiwara S, Ohashi K, Mizuno K. Solo and Keratin Filaments Regulate Epithelial Tubule Morphology,
Cell Struct Funct, 2;43(1):95-105. (2018)
・Kato K, Dong B, Wada H, Tanaka-Matakatsu M, Yagi Y, Hayashi S. Microtubule-dependent balanced cell contraction andluminal-matrix modiﬁcation accelerate epithelial tube fusion, Nature Communications, 7, 11141. (2016)

Biomolecular Dynamics Simulation GroupOKUMURA, Hisashi
Biomolecules such as proteins and peptides have complicated free-energy landscape withmany local minima. The conventional canonical-ensemble molecular dynamics (MD)simulations tend to get trapped in a few of the local-minimum states. To overcome thesediﬃculties, we have proposed new generalized-ensemble algorithms, such as
replica-permutation method. We apply these methods to proteins and peptides and try to
predict the native structures of proteins.
We are also interested in protein aggregates such as
oligomers and amyloid ﬁbrils, which are associatedwith more than 20 human neurodegenerative
diseases. To understand formation and disruption ofthese protein aggregates, we perform MD
simulations of these systems.
References：3Amyloid ﬁbril of amyloid-β peptides.

・H. Okumura and S. G. Itoh, Structural and ﬂuctuational diﬀerence between two ends of Aβ amyloid ﬁbril: MD simulation predicts only one
end has open conformations, Sci. Rep. 6, 38422. (2016)
・H. Okumura and S. G. Itoh, Amyloid ﬁbril disruption by ultrasonic cavitation: Nonequilibrium molecular dynamics simulations,
J. Am. Chem. Soc. 136, 10549-10552. (2014)
・S. G. Itoh and H. Okumura, Replica-permutation method with the Suwa-Todo algorithm beyond the replica-exchange method,
J. Chem. Theory Comput. 9, 570-581. (2013)

Department of Creative Research
Biomolecular Organization Research Group
KATO, Koichi
Living systems are characterized by the dynamic assembly and disassembly of various
self-organized biomolecules in response to external environmental changes.
Omics-based approaches developed in recent decades have provided a comprehensive
understanding of biomolecules as parts of living organisms. However, fundamental
questions concerning how these biomolecules are ordered autonomously to form
ﬂexible and robust systems remain unanswered. To acquire an integrative
understanding of the principles underlying biomolecular organization, we employ
multidisciplinary approaches based on detailed analyses of dynamic structures andinteractions of biomolecules using molecular and cellular biology techniques
accompanied by synthetic and computational techniques.
References：
・Kato, K., Yanaka, S. and Yagi, H.
Technical basis for nuclear magnetic resonance approach for glycoproteinsExperimental Approaches of NMR Spectroscopy, 415-438 (2018)
・Kato, K. and Satoh, T.
Structural insights on the dynamics of proteasome formation
Biophys. Rev., 10, 597-604 (2018)

Cardiocirculatory Dynamism Research GroupNISHIDA, Motohiro
Cardiocirculatory system is precisely maintainedby the multilevel interactions among muscularorgans including heart, blood vessels, and skeletal
muscles. We aim to elucidate the mechanisms ofstress resilience (i.e., recovery from ischemic andmechanical stress) in cardiocirculatory systems.
We aim to elucidate molecular mechanisms
underlying regulation of cardiovascular risks bysulfur-based electrophilic/nucleophilic
modiﬁcations of proteins. We also aim toelucidate the mechanism how exercise promotes
vasculogenesis after ischemic stress, and establish

Capillary arterialization after hindlimb ischemia
in TRPC6-deﬁcient gastrocnemii.

an exercise-mimetic therapeutic strategy.
References：
・Nishimura A et al. Hypoxia-induced interaction of ﬁlamin with Drp1 causes mitochondrial hyperﬁssion-associated myocardial
senescence. Science Signal. 11, eaat5185. (2018)
・Shimauchi T et al. TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy. JCI Insight. Aug 3;2(15). pii: 93358. (2017)
・Nishimura A et al. The purinergic P2Y6 receptor heterodimerizes with the angiotensin AT1 receptor to promote angiotensin II-induced
hypertension. Science Signal. 9(411), ra7. (2016)4

Department of Creative Research
Cognitive Genomics Research GroupGO, Yasuhiro
Spatiotemporal transcriptome gene regulations are essential for the construction ofbrain structure and for proper function. Comprehensive analyses of the dynamics andthe architecture of transcriptome in the both wild and diseased animal models also leadto understanding the molecular causality of the human neuropsychiatric disease.
Currently we examine the spatiotemporal transcriptome dynamics using the primate
brain to identify the spatiotemporal-speciﬁc modulating genes from macro-scale tosingle-cell level. Through this study, we aim to identify the molecular dynamics andtrajectories between proper and atypical brain gene expressional networks. Additionally,
we perform massive population genetic analysis for the neuropsychiatric related genes
in primates to identify an individual that has a spontaneous loss-of-functional (LoF)
mutation in the neuropsychiatric genes and aim to make disease primate models for theReferences：

neuropsychiatric disease.

・Xu C, Li Q, Eﬁmova O, He L, Tatsumoto S, Stepanova V, Oishi T, Udono T, Yamaguchi K,
Shigenobu S, Kakita A, Nawa H, Khaitovich P, Go Y. Human-speciﬁc features of spatial gene
expression and regulation in eight brain regions. Genome Res. 28: 1097-1110. (2018)
・Tatsumoto S, Go Y, Fukuta K, Noguchi H, Hayakawa T, Tomonaga M, Hirai H, Matsuzawa T,
Agata K, Fujiyama A. Direct estimation of de novo mutation rates in a chimpanzee
parent-oﬀspring trio by ultra-deep whole genome sequencing. Sci Rep. 7(1): 13561. (2017)
・Yoshida K, Go Y, Kushima I, Toyoda A, Fujiyama A, Imai H, Saito N, Iriki A, Ozaki N, Isoda M.
Single-neuron and genetic correlates of autistic behavior in macaque. Sci Adv. 2(9): e1600558.
(2016)Developmental Signaling Research GroupTAKADA, Shinji

The most popular model to explain the patterning process is the “morphogen gradient andthreshold” theory. Many genetic results indicate that secreted signal proteins, including Wnt,
FGF, BMP, and Hh, function as morphogens. In spite of the accumulation of genetic
evidence, however, the mechanism of morphogen transport, as well as the characteristics ofmorphogen molecules themselves, remain to be elucidated. One of our major goals is toreveal the real image of morphogens and the molecular mechanism underlying theformation of morphogen gradients, including the secretion and extracellular transport ofthese morphoge.

References：
・Takada, R., Mii, Y., Krayukhina, E., Maruyama, Y., Mio, K., Sasaki,Y., Shinkawa, T., Pack, C.-G., Sako, Y., Sato, C., Uchiyama, S.,
Takada, S. Commun. Biol. 1, 165 (2018)
・Mii, Y., Yamamoto, T., Takada, R., Mizumoto, S., Matsuyama, M.,
Yamada, S., *Takada, S., & *Taira, M. (*Co-corresponding
authors) Nature Commun. 8, 1973. (2017)
・Yabe, T., Hoshijima, K., Yamamoto, T., & Takada, S.
Development 143, 2842-2852. (2016)

5Deﬁciency in Wnt secretion causes abnormal
development

Wnt proteins require speciﬁc apparatus
in secretionDepartment of Creative Research
Dynamic Molecular Neurobiology GroupSHIINA, Nobuyuki
The transport of speciﬁc mRNAs and local control of translation in neuronal dendrites
represent an important gene expression system that provides localized protein
synthesis in dendrites at just the right time and place. This system controls the location
at which neurites will connect to each other, thereby forming neural networks. The
speciﬁc mRNAs are recruited into “RNA granules” in neuronal dendrites. We areresearching RNA granule factors regulating mRNA transport and local translation, theirtarget mRNAs, and the mechanisms of localized protein synthesis using mice in order
to better understand its relation to the formation of synapses and neural networks,
memory, learning, and behavior.
References：
・Nakayama K, Ohashi R, Shinoda Y, Yamazaki
M, Abe M, Fujikawa A, Shigenobu S,
Futatsugi A, Noda M, Mikoshiba K,
Furuichi T, Sakimura K and Shiina N. eLife 6,
e29677 (2017).
・Ohashi R, Takao K, Miyakawa T and Shiina N.
Sci. Rep. 6, 20775 (2016).

A conditional knockout (cKO) mouse of RNG105, an RNA granule component (A) and brain
hippocampal areas stained with an anti-RNG105 antibody (B).

Metallobiology GroupAONO, Shigetoshi

Transition metal ions and

(A)

(B)

(C)

(D)

metalloproteins play crucial roles inmeeting the energy demands of the cellby playing roles in intermediarymetabolism and in signal transduction
processes. The elucidation of thestructure and function of these
metalloproteins is central to understanding the regulatory
mechanisms associated with biological functioning. We are
currently elucidating the structure-function relationships ofmetalloproteins using experimental methods in the areas ofbiochemistry, molecular biology, structural biology, inorganic
chemistry, and physical chemistry. Our research interest is
especially focusing on transition metal ion-containing

References：
・Andrea Pavlou, Andreas Loullis, Hideaki Yoshimura,transcriptional regulators, heme-based gas sensor proteins, andShigetoshi Aono, and Eftychia Pinakoulaki,transition metal ions/complexes transport systems.

Biochemistry, 56, 5309-5317. (2017)
・N. Muraki, C. Kitatsuji, S. Aono, J. Porphyrins &Phthalocyanines., 19, 9-20. (2015)
・N. Muraki, S. Aono, Chem. Lett., 45, 24-26. (2015)6

Department of Creative Research
Neuronal Networks Research GroupHIGASHIJIMA, Shin-ichi
Using zebraﬁsh, we are studying
the morphology and functional
properties of spinal neurons that
express a particular transcription
factor. Central to our approach is
to visualize transcription factor
positive cells by making
transgenic zebraﬁsh that express
ﬂuorescent proteins in these cells. Such transgenic
ﬁsh allow us to trace development of speciﬁc types ofneurons, and allow us to perform targetedelectrophysiological recordings. We also use
optogenetic tools such as ChR2 and halo-rhodopsin
to manipulate activity of speciﬁc types of neurons.

A class of inteneurons are easily identiﬁed by
ﬂuorescence of GFP in live animals

References： ・T. Shimazaki, M. Tanimoto, Y. Oda, and S. Higashijima. "Behavioral role of the reciprocal inhibition between apair of Mauthner cells during fast escapes in zebraﬁsh" Journal of Neuroscience, 39, 1182-1194. (2019)
・Y. Kimura and S. Higashijima. Nature Communications, in revision

Protein Design Group
KOGA, Nobuyasu

Protein molecules spontaneously fold into unique three-dimensional structures speciﬁed bytheir amino acid sequences from random coils to carry out their functions. Many of protein
studies have been performed by analyzing naturally occurring proteins. However, it isdiﬃcult to reach fundamental working principles of protein molecules only by analyzing
naturally occurring proteins, since they evolved in their particular environments spending
billions of years. In our lab, we explore the principles by computationally designing protein
molecules completely from scratch and experimentally assessing how they behave.

References：
・N. Koga, R. Tatsumi-Koga, G. Liu, R. Xiao, T. B. Acton, G. T.
Montelione and D. Baker*, Nature 491, 222‒227 (2012)
・Y.-R. Lin, N. Koga*, R. Tatsumi-Koga, G. Liu, A. F. Clouser,
G. T. Montelione and D. Baker*, Proc. Natl. Acad. Sci. U. S.
A. 112, E5478‒E5485 (2015)
・Y.-R. Lin, N. Koga, S. M. Vorobiev and D. Baker*, Protein
Sci. 26, 2187‒2194 (2017)7

Department of Creative Research
Quantitative Biology GroupAOKI, Kazuhiro
A living cell acts as an input-output (I/O) unit, which senses environment and internal
states, processes information, and responds appropriately to adapt the changes. Ourlaboratory is interested in such a system for the information processing controlled byintracellular signaling devises and networks. Especially, we focus on several signaltransduction pathways related to cell proliferation, diﬀerentiation, and cell death inmammalian cells, and aim to quantitatively decipher the mechanisms of signaling networks
governing cellular decision-making. To this end, we are attempting to visualize, manipulate,and simulate intracellular signaling with ﬂuorescence imaging techniques andcomputational approaches.

FRET

YFP

CFP

475 nm433 nm

530 nm433 nmReferences：
・Miura H, Kondo Y, Matsuda M, Aoki K. Cell-to-cell heterogeneity in p38-mediated

Liganddomaincross-inhibition of JNK causes stochastic cell death. Cell Reports, 24:2658-2668. (2018)

0 min

・Aoki K, Kondo Y, Naoki H, Hiratsuka T, Itoh RE, Matsuda M. Propagating Wave of ERK

SensordomainLinker

4 min

8 min

Activation Orients Collective Cell Migration. Developmental Cell, 43, 305‒317. (2017)
・Uda Y, Goto Y, Oda S, Kohchi T, Matsuda M, Aoki K. Eﬃcient synthesis ofphycocyanobilin in mammalian cells for optogenetic control of cell signaling.
Proc Natl. Acad. Sci. U.S.A., 114 (45) 11962-11967. (2017)(Upper) Structure of intramolecular FRET biosensor.
(Lower) Spatiotemporal Rac1 activity in a migrating cell.

Spatiotemporal Regulations GroupNONAKA, Shigenori

Our main interest is the mechanism how the initialleft-right asymmetry is determined in mammaliandevelopment. A small patch in a gastrulating mouseembryo called ʻthe nodeʼ generates leftward ﬂuid
ﬂow by vortical motion of primary cilia on its ventral
surface, and the ﬂow direction is critically importantto subsequent asymmetric gene expression andﬁnal organ arrangement. We are currently focusedon the mechanism how the ﬂow is converted to theasymmetric gene expression, i.e. what kind of
information is conveyed by the ﬂow, chemical ormechanical or something else, by combining
techniques including whole embryo culture,light-sheet microscopy, etc.

Self-made light-sheet microscope

References：・Ichikawa, T., Nakazato, K., Keller, P.J., Kajiura-Kobayashi, H., Stelzer, E.H., Mochizuki, A., and Nonaka, S. Live imaging and quantitative analysis
of gastrulation in mouse embryos using light-sheet microscopy and 3D tracking tools. Nat Protoc 9, 575-585. (2014)
・Takao, D., Nemoto, T., Abe, T., Kiyonari, H., Kajiura-Kobayashi, H., Shiratori, H., and Nonaka, S. Asymmetric distribution of dynamic
calcium signals in the node of mouse embryo during left-right axis formation. Developmental Biology 376, 23-30. (2013)8

Department of Creative Research
Thermal Biology GroupTOMINAGA, Makoto
We mainly investigate molecularmechanisms of thermosensation andnociception by focusing on TRP ion
channels. We are trying to clarify themolecular mechanisms ofthermosensation and their
physiological signiﬁcance by focusing
on the thermosensitive TRP channels
from mammals to insects. We are also trying to clarify thenociceptive mechanisms at peripheral nerve endings byfocusing on TRPV1 and TRPA1. We are doing behavioral
analyses of mice lacking the thermosensitive TRP channels.
Furthermore, we are cloning the thermosensitive TRP
channels genes from various species, which would help us
to understand the mechanisms of thermosensation in theevolution. We also utilize fruit ﬂies as a model to investigate
temperature preference and adaptation, particularly
focusing on regulatory roles of lipid components.

References：
・Derouiche S. et al, TRPV4 heats ups ANO1-dependent exocrine
gland ﬂuid secretion. FASEB J. 32 (4): 1841-1854. (2018)
・Maruyama K. et al, The ATP transporter VNUT mediates
induction of Dectin-1-triggered Candida nociception. iScience
6: 306-318. (2018)
・Sokabe T. et al, A switch in thermal preference in Drosophila
larvae depends on multiple rhodopsins. Cell Rep 17 (2):336-344. (2016)

Biomolecular Interaction Research GroupUCHIYAMA, Susumu

We have been studying dynamic protein assembly using native mass spectrometry (nativeMS) that provides mass of biological complexes such as protein complex formed throughnon-covalent interactions. With native MS we can obtain the high resolution information on
mass of complex molecule, from which stoichiometry of the complex are identiﬁed.
Assembly of not only biological molecules but also of synthetic molecules has been
determined with high accuracy using native MS. Researchers who are highly interested innative MS can potentially ask to perform native MS at this research center under thecollaboration scheme.
References：
・Ishii, K., Zhou, M, and Uchiyama S. Native mass spectrometry forunderstanding dynamic protein complex. BBA General subjects
1862, 275-286. (2018)
・Uchihashi T, Watanabe YH, Nakazaki Y, Yamasaki T, Watanabe T,
Maruno T, Ishii K, Uchiyama S, Song C, Murata K, Iino R, Ando T.
Dynamic structural states of ClpB involved in its disaggregation
function. Nature Communications 9, Article number: 2147. (2018)
・Zhan, Y., Ogata, K., Kojima, T., Koide, T., Ishii, K., Mashiko, T.,
Tachikawa, M., Uchiyama, S., Hiraoka, S. Hyperthermostable

9

Cube-shaped Assembly in Water. Communications Chemistry 1,
Article number: 14. (2018)

Department of Creative Research
Plant Development and Physiology Research GroupTSUKAYA, Hirokazu / KAWADE, Kensuke
Emerging evidences depict that each developmental process requires speciﬁc regulation of
metabolism most likely to produce signaling molecules and/or to support the progression
itself. Despite an importance, less attention has been paid to this relationship due to an
insuﬃcient interaction between development and metabolism research ﬁelds. The aim of ourlaboratory is to understand how metabolic systems are coordinately modulated with
developmental progression. To address this, we are carrying out genetic screening using!"#$%&'()%)*+,#-%#.# as a model experimental system to explore as-yet-unknown relationshipbetween development and metabolism. Also, cutting-edge techniques including
metabolomics, together with solid biochemistry and molecular biology, are currently working to know the functionalsigniﬁcance of speciﬁc metabolism in development of multicellular organisms.
(a)

(b)

(c)

(d)

(e)

References：
・Ali Ferjani*, Kensuke Kawade, Mariko Asaoka, Akira Oikawa,Takashi Okada, Atsushi Mochizuki*, Masayoshi Maeshima,
Masami Yokota Hirai, Kazuki Saito, and Hirokazu Tsukaya.
Scientiﬁc Reports, 8; 14696. (2018)(a) A model plant, !"#$%&'()%)*+,#-%#.#* (b) AN3 protein (green) is a signaling moleculefor proliferation of leaf cells (magenta). (c) The #./ mutant shows unstable seed
pigmentation, suggesting an involvement of this protein also in metabolism. (d) Blue
indicates that AN3 is expressed in root tip. (e) Metabolism of branched chain aminoacids might be regulated by the AN3 in the root tip.

・Kensuke Kawade*, Yimeng Li, Hiroyuki Koga, Yuji Sawada,
Mami Okamoto, Ayuko Kuwahara, Hirokazu Tsukaya, andMasami Yokota Hirai*. Development, 145(17), dev168369.
(2018)
・Kensuke Kawade*, Hirokazu Tanimoto, Gorou Horiguchi,
and Hirokazu Tsukaya.
Biophysical Journal, 113; 1109-1120. (2017)

Biofunctional Systems Construction Research Group
SATO, Koji

The senses of olfaction and gustation are
essential chemosensory systems torecognize the tens of thousands ofchemical compounds in nature. The
genes of olfactory receptors (ORs)encode the large a large family ofseven-transmembrane-domain G protein
coupled receptors (GPCRs). However insect ORs possess theseven transmembrane topology with the intracellular amino
terminus, and comprise the odor-gated ion channels (ﬁg. 1).
We focus on the molecular mechanism of signal transduction inchemical senses, which enable the complex neuronal coding ofFig. 1 Schematic model for ligand-gated channel
properties of the insect conventional OR + olfactory
co-receptor (Orco) complex.

multiple of chemical information.
References： ・Sato, K. (correspondence) and Sorensen, P.W. Chemical Senses, 43:249-260. (2018)
・Sato, K. and Takeuchi, S. Angewandte Chemie International Edition, 53:11798-11802. (2014)(Selected as the Hot Paper and Inside Back Cover of the issue.)・Sato, K., Pellegrino, M., Nakagawa, T., Nakagawa, T., Vosshall, L.B., and Touhara, K. Nature 452:1002-1006. (2008)10

Department of Creative Research
Constructive Biology GroupKURIHARA, Kensuke
Construction of protocells, which are created from simple molecules, has drawn muchattention as part of researchersʼ ongoing exploration of lifeʼ s origins and the creation ofartiﬁcial life. Such protocells are assumed to have replicating systems of information andproducing systems of compartments via metabolic systems. As advanced protocell models,vesicles, which are composed of amphiphiles, have been widely used due to similarities inthe structure and morphological behavior of biological cell membranes. We aim toconstruct cell-mimic vesicles from organic chemical and supramolecular approach. In thelecture, I introduce our self-reproducing vesicular system in which the production of thecatalyst intertwines with that of the vesicular membrane molecules.

References：
1) L. Sheng & K. Kurihara, Chem. Commun. 52, 7786-7789(2016)
2) L. Sheng & K. Kurihara, Chem. Lett. 45, 598-600. (2016)
3) K. Kurihara, Y. Okura, M. Matsuo, T. Toyota, K. Suzuki &T. Sugawara, Nature Commun. 6, 8352. (2015)

Nuclear Dynamics GroupMIYANARI, Yusuke
We have just open a new lab in early 2014. A
fundamental question in biology for us is tounderstand the mechanisms underlying cell-fatedecision. Genomic reprogramming after
mammalian fertilization reverts terminallydiﬀerentiated gametes into toti- or pluripotent
state to start a new developmental program. The
cell lineage allocation is accompanied by drasticchanges in the pattern of gene expression, epigenetic conﬁgurations,and nuclear organization. We are interested in a “microscopic” view of
the nuclear architecture, which is subnuclear distribution of chromatin
and studying functional roles of nuclear dynamics in celllineage-allocation by deciphering the molecular mechanisms
underlying remodeling of nuclear organization and their eﬀects ondevelopmental gene expression, using mouse embryos and ES cells as
model systems.

11

References：
1 Miyanari Y,
A New Approach to Dissect Nuclear Organization:
TALE-Mediated Genome Visualization (TGV). Methods
Mol Biol. 2016;1338:89-97.
2 Miyanari Y,
TAL eﬀector-mediated Genome Visualization (TGV)
Methods, 2014, Sep;69(2):198-204.
3 Miyanari Y#, Birling CZ. And Torres-Padilla ME*,
Live visualization of chromatin dynamics using
ﬂuorescent TALEs, Nature Structural & Molecular
Biology. 2013 Nov;20(11):1321-4.
#Corresponding authors. Highlighted by Nature Methods.
4 Li Y#, Miyanari Y#, Shirane K, Nitta H, Kubota T, Ohashi H,
Okamoto A, Sasaki H. Sequence-speciﬁc microscopic
visualization of DNA methylation status at satellite
repeats
in individual cell nuclei and chromosomes,Nucleic Acids
Res. 2013 Oct;41(19):e186. # First authorship
5 Miyanari Y, Torres-Padilla ME.
Control of ground-state pluripotency by allelic regulationof Nanog. Nature. 2012 Feb 12;483(7390):470-3
6 Miyanari Y, Torres-Padilla ME.
Epigenetic regulation of reprogramming factors towards
pluripotency in mouse preimplantation development.
Curr Opin Endocrinol Diabetes Obes. 2010 Dec;
17(6):500-6
7 Hiura H, Sugawara A, Ogawa H, John RM, Miyauchi N,
Miyanari Y, Horiike T, Li Y, Yaegashi N, Sasaki H, Kono T,
Arima T. A tripartite paternally methylated region within
the Gpr1-Zdbf2 imprinted domain on mouseDepartment of Creative Research
Collaborative Research Group

Biomolecular Dynamics Observation Group
UCHIHASHI, Takayuki

Dynamic events on a molecular level are essential for a living system because biologicalmolecules fulﬁl a wide variety of unique functions through conformational change andmolecular interactions triggered by binding of ligand/substrate and changes in theexternal environment. We aim to elucidate function mechanisms of proteins from the
aspect of single-molecule dynamics based on direct visualization using high-speed
atomic force microscopy (HS-AFM), which enables real-time imaging of individual
molecules in action. Further, we carry out functional extensions of the HS-AFM towards
imaging dynamics of morphology and mechanical property of a living cell.
References：
・Mori T, et al, Revealing circadian mechanisms of integration and resilienceby visualizing clock proteins working in real time. Nat Commun. 9, 3245
(2018)
・Uchihashi T, et al, Dynamic structural states of ClpB involved in its
disaggregation function, Nat Commun. 9, 2147 (2018)
・Kozai T, et al, Two-step process for disassembly mechanism of proteasome
α7 homo-tetradecamer by α6 revealed by high-speed atomic force
microscopy, Sci Rep. 7, 15373 (2017)
・Shibata M, et al, Real-space and real-time dynamics of CRISPR-Cas9 visualizedby high-speed atomic force microscopy, Nat Commun. 8, 1430 (2017)12

Section for Exploration of Life in Extreme Environments
Deep-Sea and Deep Subsurface Life Research Group
TAKAI, Ken
We look for real limits of life and biosphere and boundary conditions between habitableand uninhabitable in the dark world, namely deep-sea and deep subsurface environments
by means of top-rated exploration platforms such as human-occupied submersible vehicle(HOV), remotely operative vehicles (ROV), research vessels including scientiﬁc drilling
vessels. Naturally observed limits of life and biosphere and fringe functional mechanisms
provide signiﬁcant clues to understanding universal and speciﬁc habitability of living
forms, ﬁnding unique chemical and biological systems established in the long history of
evolution and synthesizing novel artiﬁcial systems in laboratory and for application.
References：
・T Nunoura et al, A primordial and reversible TCA cycle in a facultatively
chemolithoautotrophic thermophile, Science 359 (6375), 559-563. (2018)
・K Yanagawa et al, Deﬁning boundaries for the distribution of microbialcommunities beneath the sediment-buried, hydrothermally active seaﬂoor,
The ISME journal 11 (2), 529. (2017)
・Y Takaki et al, Hadal biosphere: insight into the microbial ecosystem in the
deepest ocean on Earth. T Nunoura, Proceedings of the National Academy of
Sciences, 201421816. (2015)

Extreme Environmental Biomolecular Research Group
KATO, Koichi

Organisms living in extreme environments such as deep-sea trenches develop uniqueecological adaptation mechanisms. In addition, even in more familiar environments, someorganisms develop peculiar adaptation mechanisms to extreme environmental conditions
as exempliﬁed by cryptobiosis. We conduct biomolecular analyses to elucidate themolecular processes underlying these biological adaptation mechanisms. Furthermore, we
aim to develop biotechnological applications based on our knowledge of biomolecularsystems involved in biological processes adapted to extreme environments. Moreover, we
exploit extreme environmental conditions such as microgravity in outer space forcontrolling biomolecular processes including amyloid formation.
References：
・Yagi-Utsumi, M., Sikdar, A., Kozai, T., Inoue, R., Sugiyama, M.,
Uchihashi, T., Yagi, H., Satoh, T. and Kato, K. Conversion offunctionally undeﬁned homopentameric protein PbaA into
a proteasome activator by mutational modiﬁcation of its
C-terminal segment conformation, Protein Eng. Des. Sel.
31, 29-36 (2018)
・http://iss.jaxa.jp/en/kiboexp/news/180719̲amyloid.html

13

Joint Research Projects
Joint Research Projects of ExCELLSThe Exploratory Research Center on Life and Living
Systems (ExCELLS) promotes collaborative researchwith researchers from other institutes and universities.
Various researchers can use ExCELLS equipment toperform their own research through joint research
projects along with ExCELLS researchers.

ExCELLS Equipments(1) Combined system of high-speed atomic force
microscopy and ﬂuorescence microscopy

Notes
When presenting the results of their joint
research project, researchers must notethat the results were achieved throughthe ExCELLS joint research initiative (anexample is provided below).

(2) Q-TOF mass spectrometer for native MS※Example
This research was supported by the Joint
Research of the Exploratory ResearchCenter on Life and Living Systems(ExCELLS). (ExCELLS Programme No.***),
where *** is your programme number.
(The programme number will be provided
if your application is successful.)
Travel expenses in Japan may be paid
based on the budget set out in the NINS
regulations.
Travel expenses in foreign countries will
not be reimbursed.
Please refer to the joint research projectguideline for other notes.

(3) High-speed live imaging system(4) Total internal reﬂection ﬂuorescence (TIRF) microscope(5) Multifunctional super-resolution ﬂuorescence microscope NEW
14

Symposium & Seminar
Symposium
Frontier Bioorganization Forum 2018

Date
July 8 (Sun) ‒ 11 (Wed), 2018
Venue
Exploratory Research Center
on Life and Living Systems (ExCELLS),
National Institutes of Natural Sciences, Okazaki, Japan(5-1 Higashiyama Myodaiji, Okazaki, Aichi,
444-8787, Japan)
Organizing Committee
Koichi Kato (ExCELLS, IMS)
Shigetoshi Aono (ExCELLS, IMS)
Motohiro Nishida (ExCELLS, NIPS)
Kazuhiro Aoki (ExCELLS, NIBB)
Maho Yagi-Utsumi (ExCELLS, IMS)
Co-organizers
IMS Asian International Symposium
10th Korea-Japan Seminar on Biomolecular Science
Joint partner
JSPS Grant‐in‐Aid for Scientiﬁc Research on Innovative Areas

ExCELLS Young Scientists Forum 2018

Date
July 10 (Tue), 2018
Venue
Exploratory Research Center on Lifeand Living Systems (ExCELLS),
National Institutes of Natural Sciences,
Okazaki, Japan(5-1 Higashiyama Myodaiji, Okazaki, Aichi,
444-8787, Japan)
Organizing Committee
Maho Yagi-Utsumi (ExCELLS, IMS)
Saeko Yanaka (ExCELLS, IMS)
Tomohiro Tanaka (ExCELLS, NIPS)
Yohei Kondo (ExCELLS, NIBB)Haruko Miura (Kyoto University)
Rina Yogo (Nagoya City University)
Taichiro Sekiguchi (SOKENDAI)

15

Co-organizers
Frontier Bioorganization Forum 2018

Symposium & Seminar
Symposium
The 1st ExCELLS Symposium

Date
15th Oct. 2018 (Mon) ‒ 16th Oct. 2018 (Tue)
Venue
Okazaki Conference Center(Address: Azatenma 8-1, Myodaiji, Okazaki
444-0864, Japan)
Organizing Committee
Motohiro Nishida (ExCELLS, NIPS)
Shin-ichi Higashijima (ExCELLS, NIBB)
Hisashi Okumura (ExCELLS, IMS)
※Language: Japanese16Symposium & Seminar
ExCELLS Seminar

The 1st ExCELLS Seminar
Date: 2nd,July, 2018
Speaker: Dr. Satoshi Toda
(Department of Cellular and Molecular Pharmacology
University of California, San Francisco)
The 2nd ExCELLS Seminar
Date:2nd August, 2018
Dr. Ryuji Kawano(Tokyo University of Agriculture and Technology)
The 3rd ExCELLS Seminar
Date: 21st September, 2018
Dr. Ken Takai(JAMSTEC)The 4th ExCELLS Seminar
Date: 21st December, 2018
Prof. Dr. Azusa Kamikouchi(Nagoya University)

ExCELLS Research Meeting

The 1st ExCELLS Research Meeting“Dormant and Metabolism Research Meeting”
Date: 15th, November, 2018
Speaker:Prof. Dr. Yoshifumi Yamaguchi (Hokkaido University)
Dr. Genshiro Sunagawa (Riken)
Prof. Dr. Toshihiko Fujimori (NIBB)
Prof. Dr. Tohru Ishitani / Dr. Masayuki Oginuma(Gunma University)
Dr. Masamitsu Fukuyama (The University of Tokyo)

17

ExCELLS Floor Map
9Welcome to ExCELLS.
When you enter the building, please take oﬀ
your outdoor shoes and change into slippers .

a
Shiin
de

Kawa

ijima

h
Higas

Sato

8

Koga
ka

Nona

ra

u
Okum

7

Go

naga

Tomi

nari

Myodaiji Campus

Miya

6

Kato

Ohta

a

Takad

5
Aoki

4

Director

Kato

3

ara

Kurih

Aono
Seminar Room

Seminar Room

2

ama

Uchiy
Native MSda

HS-AFM

Nishi

West EntranceWest Side

ashi

Uchih

Vending Machine

1
East Side

EL

bldg.1

bldg.2
East Entrance

bldg.3

bldg.4

bldg.5NO OUTDOOR FOOTWEAR!

Please Change into Slippers

18

ACCESS
Nagoya Sta.

Meitetsu Train（about 30 min by express）

Meitetsu Train

Toyohashi Sta.

（about 30 min
by express）

Higashi- （Tatsumigaoka-Junkan Bus）
Okazaki Meitetsu Bus Tatsumikita
ExCELLS
about 5 min
about 3 min
Sta.
1chomeon foot

Meitetsu Airport Bus（To JR Okazaki Sta.）

Central Japan
International
Airportabout 20 min on foot（about 80 min）

By CarCar（about 10 min）

Okazaki IC

From the south exit of Higashi-Okazaki station,
・By taxi : About 7 min.
・By bus : Take Tatsumigaoka-jyunkan, which departs from No11 bus station, and get oﬀ at Tatsumi-kita-1chome(about 5 min), and walk to the east for about 3min.
・On foot : About 20 min.

Okazaki City HallTo Nagoya

Tonobashi
BridgeMyodaiji-cho

1

Fukiyabashi
BridgeSouth Exit

M

Rokusho Shrine

NIBB

ei

Mishima ES
Entrance

Oto River

te

ts

u

N

Mishima Lodge

NIPS
MyodaijiCampusOkazakiInterchangeWest

North Exit

HigashiOkazaki Sta.

IMS

Okazaki JHS

ag

oy

a

OkazakiHigh
SchoolHigashi
Myodaiji-cho

ExCELLSExCELLs
Yamate Campus

Tatsuminishi
1-chome

Edited by ExCELLS

http://www.excells.orion.ac.jp

Mishima ES

Tatsumi JHS

Issued in February 2019

Otogawa
BridgeLi
ne

Okazaki
ConferenceCenterMyodaijiLodge

To Toyohashi

Tatsumikita
2-chomeOnishi 3

5-1 Higashiyama, Myodaiji,
Okazaki, Aichi, 444-8787, Japan
National Institutes of Natural Sciences
Exploratory Research Center on Life and Living Systems