Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Antibacterial lead discovery with D/L-peptide libraries (D/L-PEPTIDE LIBRARY)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-09-01
End date: 2010-06-30
Duration (months): 10.0
Total project cost (EUR): 127813.76
EU funding (EUR): 127813.76
Participants: 1
Project status: CLOSED

Nowadays, a multitude of examples for targeting enzymes with small molecules is known, whereas the direkt access to macromolecular interaction, such as DNA/protein, RNA/protein and protein/protein within the cell still waits to be solved by generic methods. We intend to create a toolbox for targeting these interactions with D-/L-peptides, a new class of biostable oligomer ligands. Initially we will establish split-and-pool libraries using postsynthetic dimerization of two orthogonal pairing partners which can be expected to form stable folds of the size of interactive protein subdomains. In a second approach, specific target functions and interaction domains will be used to generate new ligands by design and structural analogy. Folding and secondary structure preference of the most potent constructs will be elucidated (CD, NMR, FRET) to deduce preferences for pairing, minimal sequence length, and composition. Macromolecular targets and activity will be further studied using fluorescence microscopy and protein binding assays.

Keywords: bioorganic chemistry,d/l-peptides,peptide synthesis,library screening,structure-activity relationships,antimicrobial peptides
Re-Evolution of a Non Ribosomal Protein Synthethase (NRSREVO)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-05-15
End date: 2011-05-14
Duration (months): 24.0
Total project cost (EUR): 171867.63
EU funding (EUR): 171867.63
Participants: 1
Project status: CLOSED

Many peptide-based natural products of therapeutic importance are synthesised by nonribosomal peptide synthetases (NRPSs), large, multifunctional enzymes that operate as molecular assembly lines, by coupling and processing an extending chain of amino acid monomers. They are composed of numerous enzyme domains that carry out the steps of the bio-synthesis and provide an efficient route to natural products that are not easily accessible by synthetic chemistry. An efficient exploitation, however, still requires a much deeper understanding of the molecular basis of activity and specificity in NRPS enzymes. A set of approaches dealing with neutral drift, directed evolution and selective enzyme modification will be carried out on the model system TycA, taking advantage of knowledge and technologies available at the host institution as well as through a number of international collaborations and participation in the training programme of the FP7 network ENEFP (dealing with directed evolution of functional proteins).

Keywords: molecular evolution,molecular design,de novo design,nonribosomal peptide synthetases,tyca,tyrocidine biosynthesis,neutral drift,catalytic promiscuity
AROMATIC FOLDAMERS AS DRUG DELIVERY CARRIERS (HELICAL TRANSPORTERS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-04-01
End date: 2011-03-31
Duration (months): 24.0
Total project cost (EUR): 164877.53
EU funding (EUR): 164877.53
Participants: 1
Project status: CLOSED

The Huc group is a world leading research team in the fields of Biomimetic and Bioorganic Chemistry. One of group’s main contributions is focused on the synthesis, structural elucidation and biological application of aromatic oligoamides. These compounds adopt exceptionally stable folded conformations, helices, stabilised by intramolecular hydrogen bonds and - interactions. The high structural predictability, tunability, ease of synthesis and resistance to hydrolysis of such foldamers has led to an increasing attention towards those oligoamides. Very recently, Huc and co-workers have proven that despite the high hydrophobicity of those aromatic foldamers, they can be made highly hydrosoluble by inserting cationic side chains, providing important possibilities for their biological application as cell penetrating agents. This project focuses on the investigation of structural characteristics and the ability of aromatic oligoamides to cross the cellular membrane and deliver different cargoes efficiently. The qualitative and quantitative determination of uptake of the helices, intracellular trafficking and translocation of cargo will very importantly allow us to gain an insight into the kinetics and mechanism underlying the cellular translocation, areas that are currently being subject to a lot of controversy. The project is concerned with an emerging area of interdisciplinary chemical research in which the development of drug delivery technologies based on the new understanding of cross-membrane transport is expected to have a very strong impact on health and the design of novel therapeutic and diagnostic agents.

Keywords: aromatic foldamers,membrane translocation,drug delivery
Rational Design and Synthesis of Zeolitic Imidazolate Frameworks (ZIFs): an experimental and statistical approach (DASZIF)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-09-01
End date: 2011-08-31
Duration (months): 24.0
Total project cost (EUR): 172434.64
EU funding (EUR): 172434.64
Participants: 1
Project status: CLOSED

One of the novel and most promising alternatives to combine the advantages of microporous zeolites and metal organic frameworks (i.e., high porosity, framework diversity, transition metal centers and tailored linkers) resides in the nanoporous imidazole-based MOFs: zeolitic imidazole frameworks (ZIFs). ZIFs comprise a network of corner units (transition metals) and linker units (imidazole molecules which can be further functionalised) that allow a manifold of frameworks due to their structural analogy to zeolites). ZIFs offer many interesting and promising features compared with other porous materials, such as the possibility to tailor these materials for specific applications; different framework zeolite structures, with different cavities and windows; and exceptional chemical stability in refluxing organic solvents, water, and aqueous alkaline solution, compared with other MOFs. Yet to date, the discovery of promising novel porous materials for specific adsorption applications is happening by trial and error rather than by rational design. In this way, molecular simulations provide an outstanding tool to predict the performance of the materials and, like so, to select the optimal structures for a given application. This project will address three objectives: i) identify optimal ZIFs structures through the simulation of its adsorption performance, ii) the synthesis and characterisation of pre-selected ZIFs using different computational and experimental techniques, iii) the assessment of their performance for industrial applications by simulations and experiments. More specifically, the target applications are: a) gas separation of CO2/CH4 and xylenes mixtures as well as gas purification; b) storage of CH4 and H2; c) capture of CO2. The novelty of this work lies in the synergetic combination of tools from different areas and disciplines to produce advances that are of both fundamental scientific interest and of engineering relevance in industrial applications

Keywords: computational chemistry,environmental chemistry,organometallic chemistry,chemical engineering,materials engineering,nanotechnology,carbon dioxide capture,storage,disposal (climate change)
New catalytic strategies for chemical synthesis: Enantioselective Organocatalytic Dearomatization – From flat molecules to complex 3-D architectures in a single step. (3DSSS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-03-01
End date: 2011-01-31
Duration (months): 23.0
Total project cost (EUR): 171867.63
EU funding (EUR): 171867.63
Participants: 1
Project status: CLOSED

Despite the changing face of organic chemistry one aspect remains persistent: the ability to make molecules to order is something that, even now, is still unique to the synthetic chemist. What is changing in synthesis is the way that we go about achieving our goal. The use of catalysts to control the synthesis of architecturally complex and enantiopure molecules is a key aspect for the future of organic chemistry. Not only does this concept impact strongly on all aspects of chemical synthesis but also the continued development of chemical biology, medicinal chemistry and materials science. The challenge for the synthetic chemist is to develop novel strategies for complex molecule synthesis that combine the factors of atom economy, catalysis and stereocontrol.

Keywords: carbon chemistry,organocatalytic reactions,organic chemistry,enantioselective synthesis,complex 3d molecules
The structural and dynamical ensemble of an amyloidogenic intermediate (AMYLOIDINTERMEDIATE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-07-01
End date: 2010-02-28
Duration (months): 8.0
Total project cost (EUR): 171867.63
EU funding (EUR): 171867.63
Participants: 1
Project status: CLOSED

Proteins and peptides have a generic tendency to convert from their soluble states into well-organized aggregates characterized by a fibrillar morphology and an extended cross-beta structure. Such transitions can give rise to over 40 pathological conditions ranging from neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, polyQ disease, to systemic amyloidoses, including light chain amyloidosis and hemodyalisis-related amyloidosis. Unveiling the origins of amyloid disorders is one of the top scientific challenges. It is clear that a better understanding of the molecular mechanisms of protein and peptide aggregation into amyloid fibrils will allow optimal therapeutic strategies and the development of better drugs to combat these disorders. Nevertheless, despite the huge efforts of the scientific community, the molecular determinants underlying these processes are still largely obscure. The aim of the present project is to determine, at an atomic level, the structural and dynamical ensemble of the amyloidogenic intermediate of a novel Acilphosphatase, the AcPDro2. This protein represents a prototype of for studying the aggregation via native-like conditions, a major aggregation pathway in vivo. The project will be performed in the lab of prof. C.M. Dobson (University of Cambridge) and will be based on a multidisciplinary approach of experiments (basically solution-NMR) and molecular simulations to characterize the conformational ensembles adopted along the AcPDro2 aggregation pathway. This study will provide the atomic description of the molecular determinants of AcPDro2 aggregation into amyloid structures. Moreover, an appealing part of the project will focus on the mode of actions of a small ligand, the phosphate, which is able to inhibit the AcPDro2 aggregation. This determination will represent an unprecedented information with implications in the field of drug design for targeting amyloid-linked diseases.

Keywords: biophysics,amyloid,free energy,solution ensembles of proteins,nmr,molecular simulations
Layer-by-layer assembly of novel bone-mimetic hydroxyapatite-fibrous clay-biopolymer hybrid membranes (CLAY BIOMIMETICS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Ireland
Call:  (FP7-PEOPLE-IIF-2008, 2008)
Start date: 2010-01-18
End date: 2011-10-17
Duration (months): 21.0
Total project cost (EUR): 251299.65
EU funding (EUR): 251299.65
Participants: 1
Project status: CLOSED

Biomimetics is a fast growing multidisciplinary field leading to the fabrication of novel materials with remarkable mechanical properties. Natural bone is a complex biomineralized system with an intricate hierarchical structure. It was widely reported that a typical secondary bone contains around 65 wt.% mineral phase, 25 wt.% organic and 10 wt.% water, among which carbonated hydroxyapatite (HAp) and collagen fibrils are the major components for the mineral and organic phases, respectively. High stiffness and large surface area fibrous clays, halloysite and sepiolite, will be used for the first time to biomimic collagen fibrils as the templates for the growth of HAp nanocrystals. Natural biopolymers, such as anionic sodium alginate, and cationic amino acids (lysine and arginine) and chitosan will be used to interact with HAp-clay composites and improve their toughness. HAp nanocrystals will be grown along the fibrous clays via co-precipitation methods, followed by preparing HAp-clay-biopolymer hybrid membranes by layer-by-layer (LBL) assembly. Processing conditions, materials composition and LBL assembly approaches will be varied to investigate their effects on structure and properties of the hybrid membranes. The chemical and crystalline structure of the HAp grown will be characterized, and its growth mechanisms in the presence of clay will be studied. Interfacial interactions among HAp, clay and biopolymer will be investigated, and the morphology of the hybrid membranes will be observed. Physical and mechanical properties, biodegradability, protein adsorbability as well as regeneration function of the membranes obtained will be measured. The resultant HAp-clay-biopolymer hybrid membranes are expected to have a good combination of stiffness and toughness through the bottom-up colloidal assembly of stiff fibrous HAp-clay with ductile biopolymers, and will have great potential in bone repair and regeneration in particular in scaffolds for tissue engineering.

Keywords: clay,biomimetics,nanocomposites,bone scaffolds,organic-inorganic hybrids,layer-by-layer assembly
Molecular mechanisms involved in the IGF-1R signalling setting of the somatotropic axis. (MISS-SA)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-IOF-2008, 2008)
Start date: 2009-09-01
End date: 2011-12-31
Duration (months): 28.0
Total project cost (EUR): 173509.69
EU funding (EUR): 173509.69
Participants: 1
Project status: CLOSED

This proposal aims to understand molecular mechanisms involved in the induction and persistence of the somatotropic function decrease observed in mice with diminished IGF-I signalling. This alteration could be induced by a specific heterozygous IGF-1R invalidation in mice brain, and in wild type mice, by a nutrient restriction during the first two weeks of life. Previous results obtained in these both models indicate that diminished IGF-I signalling first decreases hypothalamic GHRH gene expression in first 10 days of life, which alters development of somatotrophs cells in pituitary. Preliminary data indicate that this is not associated with a decrease of GHRH neurons number and suggest an alteration of gene transcription. Environmental programming of endocrine axis activity through gene transcription suggests implication of epigenetic mechanisms. Thus, using the two mice models cited above, I plan to study epigenetic modifications on the GHRH promoter (CpG methylation &amp; histones modifications). GHRH gene expression requires Ikaros that has been shown to act through changes of chromatin access. If modifications of GHRH promoter were confirmed, I will determine Ikaros gene expression by real time PCR. Next, it could be interesting to study Ikaros promoter methylation profile, since it contain 1kb CpG island. The second part of this proposal will be on mechanism involved in the persistence of somatotropic axis decrease and will focus on somatotroph cells, which are a key element of this axis. The study the GH promoter methylation profile will indicate if the gene expression alteration is associated with epigenetic changes. In this case, a particular attention will be hold to its two essentials enhancers, Ikaros and Pit-1. High throughput pyrosequencing will be use to perform these experiments. Latter, questions concerning alteration of somatotrophs proliferation/ differentiation could be raised with a widescreen MDIP array technology present at the Douglass Institute.

Keywords: neurobiology,animal growth,environmental genomics,molecular genetics
Versatile and Environmentally Friendly New Reaction Methodologies for Synthetic Organic Chemistry with Application to Natural Product Synthesis. (CASCADES)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-IOF-2008, 2008)
Start date: 2009-03-01
End date: 2011-04-30
Duration (months): 26.0
Total project cost (EUR): 172488.5
EU funding (EUR): 172488.5
Participants: 1
Project status: CLOSED

Enantioselective catalysis is the most important frontier of synthetic organic chemistry today. As nature uses enzymes to catalyze highly stereoselective reactions, it was long assumed that large and complex structures are essential to attain high enantioselectivity. However, it has now been illustrated by MacMillan and others that small molecule organic catalysts can compete with the enantioselectivity and reactivity levels of enzymes, omitting the need for highly toxic organometallic catalysts or “strong” Lewis acids. The availability of enantiopure organic chemicals as well as the academic, industrial, environmental and economic benefits of organocatalysis has shown the importance of this field of research. The combination of more than one chemical transformation into a cascade sequence is also an expanding area of research due to the reduction in cost, energy and waste. The proposed outgoing phase project would further the development of a new enantioselective organocatalytic method, within the pioneering research group of Prof. David MacMillan at Princeton. The MacMillan group have consistently been at the forefront of organocatalysis research, and thus far have pioneered over 30 catalytic asymmetric transformations of immense practicality and synthetic utility. The return phase project would highlight the importance of domino reaction sequences in organic synthesis today, with the implementation of a 3-step cascade in the total synthesis of an anti-cancer molecule. The mobility, importance of the research topic and high profile collaboration between 2 world-class research institutes would increase scientific excellence and provide opportunity to widely advertise participation in Marie Curie actions. Overall, a highly motivated European scientist would benefit greatly from both phases whilst developing many new skills. Important networks of international communication would be established, providing a platform for further collaborations in the future.

Keywords: organic chemistry,asymmetric catalysis,organocatalysis,photoredox catalysis,?-substitution,organic synthesis,diels-alder,retro-diels alder,imda,cascade reactions,environmentally friendly
Pushing the Boundaries of Molecular Dynamics Simulations (PUSHBOUND)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physical and Analytical Chemical sciences
Countries involved: Switzerland
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-08-01
End date: 2015-07-31
Duration (months): 60.0
Total project cost (EUR): 2499600.0
EU funding (EUR): 2499600.0
Participants: 1
Project status: CLOSED

Atomistic computer simulation has established itself as one of the most important methodologies in modern science, its impact being felt in areas as diverse as physics, chemistry, geophysics, materials science and biophysics, to name but a few. Yet in spite of great progress in computer power and algorithms, we are still not able to simulate such important phenomena as nucleation, phase transitions or protein folding. The purpose of this proposal is to strongly push back the limits of length, time scale and accuracy of present-day methods, greatly enhancing the scope of atomistic simulations. We expect the impact of a successful outcome of this proposal to revolutionize the field. We shall make use of three technical innovations: an extension of Langevin-type equations to include correlated (colored) noise; the use of h-matrices to speed up electronic structure calculations; and an intelligent use of neural networks. Our strategy will be complex. We plan to speed up ab-initio molecular dynamics calculations considerably and also to generate new and highly accurate effective potentials based on electronic structure calculations. A large part of our effort will be devoted to the time scale problem. In this respect we shall improve metadynamics so that its implementation becomes as general and as automatic as possible, and we shall also introduce methods for reconstructing the real dynamics from metadynamics. Finally, highly innovative and powerful sampling methods based on specially designed colored noise Langevin equations will be developed.

Keywords: molecular dynamics,ab-initio molecular dynamics