Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The role of essential DNA metabolism genes in vertebrate chromosome replication (DNAMEREP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Italy
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-06-01
End date: 2019-05-31
Duration (months): 60.0
Total project cost (EUR): 1999800.0
EU funding (EUR): 1999800.0
Participants: 2
Project status: CLOSED

Faithful chromosomal DNA replication is essential to maintain genome stability. A number of DNA metabolism genes are involved at different levels in DNA replication. These factors are thought to facilitate the establishment of replication origins, assist the replication of chromatin regions with repetitive DNA, coordinate the repair of DNA molecules resulting from aberrant DNA replication events or protect replication forks in the presence of DNA lesions that impair their progression. Some DNA metabolism genes are present mainly in higher eukaryotes, suggesting the existence of more complex repair and replication mechanisms in organisms with complex genomes. The impact on cell survival of many DNA metabolism genes has so far precluded in depth molecular analysis. The use of cell free extracts able to recapitulate cell cycle events might help overcoming survival issues and facilitate these studies. The Xenopus laevis egg cell free extract represents an ideal system to study replication-associated functions of essential genes in vertebrate organisms. We will take advantage of this system together with innovative imaging and proteomic based experimental approaches that we are currently developing to characterize the molecular function of some essential DNA metabolism genes. In particular, we will characterize DNA metabolism genes involved in the assembly and distribution of replication origins in vertebrate cells, elucidate molecular mechanisms underlying the role of essential homologous recombination and fork protection proteins in chromosomal DNA replication, and finally identify and characterize factors required for faithful replication of specific vertebrate genomic regions. The results of these studies will provide groundbreaking information on several aspects of vertebrate genome metabolism and will allow long-awaited understanding of the function of a number of vertebrate essential DNA metabolism genes involved in the duplication of large and complex genomes.

Keywords: genome instability,dna damage response,replication stress
High Impact Cross-section Calculations for Unprecedented Precision (HICCUP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Fundamental Constituents of Matter
Countries involved: Switzerland,United Kingdom
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2019-03-31
Duration (months): 60.0
Total project cost (EUR): 1514798.0
EU funding (EUR): 1514798.0
Participants: 2
Project status: CLOSED

The first runs of the Large Hadron Collider (LHC) experiment just finished. The LHC was successful in discovering a particle compatible with the Higgs boson of the Standard Model (SM). However expectations to discover New Physics have not been met so far. In order to establish whether the new resonance is the SM Higgs boson, or not, precise measurements of its properties are mandatory. These require accurate predictions for cross-sections involving the Higgs boson, as well as for SM backgrounds, that need to be subtracted accurately. Furthermore, since so far New Physics has been elusive, it will be even more important to extend the range of these searches as much as possible. This requires a solid control of SM backgrounds. This project aims at pushing the frontier of precision QCD calculations to reach an unprecedented precision for collider processes. The project is divided into two main parts. In the first part the PI will formulate a general procedure to merge different calculations at next-to-leading order (NLO) level. This will lead to the construction of an event generator for two-to-one and two-to-two scattering processes at next-to-next-to-leading order (NNLO), including parton shower corrections, essentially upgrading the POWHEG NLO generator to the NNLO level. Depending on the process considered, a significant reduction of the theoretical errors, by a factor 2-4, will be achieved. The second part focuses on extending the accuracy of resummed predictions for important QCD observables from next-to-leading logarithmic to next-to-next-to-leading logarithmic level, again achieving a substantial reduction of the theoretical error. The observables considered include, besides event-shapes and jet-rates, also jet-veto predictions in Higgs + 1 or 2 jet events. Besides the groundbreaking impact on present LHC physics measurements, these results will also be essential to match the high accuracy of measurements at a future linear collider.
A Photo-triggered On-demand Drug Delivery System for Chronic Pain (NANOHEDONISM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Products and Processes Engineering
Countries involved: Spain
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-03-01
End date: 2019-02-28
Duration (months): 60.0
Total project cost (EUR): 1570091.0
EU funding (EUR): 1570091.0
Participants: 1
Project status: CLOSED

Nerve pain affects millions of people, and can be personally devastating for people who experience it. Current methods for pain management (e.g. local injection of pain killers) are inadequate because of the short duration of action. Even sustained release treatments, such as drug-loaded liposomes, provide only one week of analgesia producing a continuous extended nerve blockade without allowing for changes in daily physical activity or level of pain relief. More importantly, such systems cannot be turned off until they run their course. In this proposal, a locally-injected or implanted near infrared (NIR)-sensitive drug reservoir that can be triggered by a simple handheld laser device applied externally is described. The device enables drug release with consistent response over multiple on/off cycles. Such a device, implanted (or eventually injected) on a nerve or near the neuraxis, could have substantial clinical impact in the treatment of chronic (or prolonged perioperative) pain. This system will consist of an impermeable ethylcellulose membrane embedded with temperature-sensitive polymer nanoparticles and NIR-active gold nanoparticles. The membrane will be engineered such that the nanoparticles form a disordered but interconnected network throughout. The gold nanoparticle concentration will be adjusted so that light-induced heating of the nanoparticles produces sufficient heat to collapse the polymer, thus opening the porous network. Those nanostructured materials which compose the device will be produced in a continuous manner by using microfluidic reactors to avoid the characteristic disadvantages when using conventional discontinuous (batch) reactors. Nanoparticle-synthesis protocols will be supported by computational fluid dynamics. The specific aims will be geared toward engineering a NIR-triggered drug release device and optimizing for a variety of drug types, then demonstrating its biocompatibility and therapeutic effectiveness in vivo.

Keywords: nanoparticles,drug eluting devices,drug delivery,plasmonics,pnipam,triggered release,microreactors,micromixers,pain,temperature responsive polymers
The Molecular Anatomy of Neurons (NEUROMOLANATOMY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and Neural Disorders
Countries involved: Germany
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2019-03-31
Duration (months): 60.0
Total project cost (EUR): 1985062.8
EU funding (EUR): 1985062.8
Participants: 1
Project status: CLOSED

The brain is nowadays the object of a number of extensive systematic studies that focus on seemingly all aspects of its morphology and function, from overall brain architecture to neuronal connections, neuronal morphology and gene expression. However, at least one basic aspect is as yet incompletely studied: the molecular anatomy of the neuron, i.e., the copy numbers and the spatial arrangement of molecules within the neuronal cell. This cannot be addressed by gene expression or proteomics approaches, as they do not have sufficient spatial precision. Electron microscopy, ideal for unraveling the neuronal morphology, does not have sufficient protein labeling efficiency. My project aims to fill this gap by a combination of super-resolution fluorescence microscopy, advanced fluorescence labelling techniques and advanced biochemistry tools such as quantitative mass spectometry. My objectives are fourfold: 1) to determine the molecular organization of at least 200 major neuronal proteins: their exact copy numbers and their position within the cell determined with nanoscale precision; 2) to generate a bank of biochemistry and microscopy sample preparations that will be available world-wide for the characterization of 1000-2000 additional proteins; 3) to integrate results into an in silico neuronal model that can be used for modelling functional neuronal parameters; 4) to use this technology to determine the changes in neuronal anatomy caused by neurodegeneration in Alzheimer’s and Parkinson’s Diseases. My group has already performed key preliminary work towards these aims. Our preliminary work focused on the synapse, where we ascertained copy numbers and positions for proteins adding up to more than 50% of the synapse’s protein mass (see figure). We are thus ready to embark on this large-scale, risk-taking project. We are confident that the in silico neuron and the preparation bank we will create will represent key new resources for future studies in neurobiology.

Keywords: super-resolution,microscopy,sted,neuron,synapse,molecular organization
Developing sequence controlled polymers for organization, templation and recognition (SCPS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Synthetic Chemistry and Materials
Countries involved: United Kingdom
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2020-01-31
Duration (months): 70.0
Total project cost (EUR): 2324271.0
EU funding (EUR): 2324271.0
Participants: 2
Project status: CLOSED

Nature‘s toolbox for replication uses DNA and RNA which are nucleic acids capable of templating new copies of themselves. Nature‘s ability to replicate has led to the evolution of a wide variety of forms and functions for biological materials which cannot be achieved using current synthetic approaches. It seems likely that if we were able to teach plastics or other polymers how to template new copies of themselves that we would similarly be able to make new, impossible materials and hence further expand the potential function and properties of these materials. These new materials would provide enhanced properties and function (such as replication and evolution) that are not currently available to material chemists. This would allow for a best-of-both-worlds scenario with the development of robust synthetic materials, with tuneable properties including crystallinity, thermal properties, shape memory, and self-healing. Most importantly, by developing an empirical and perhaps even model-based connection between polymer sequence / composition and polymer properties it would be possible to begin to design new materials in a rational and knowledge-based way. Indeed, it could be argued that this advance would ultimately solve one of the major problems in materials science, multiscale modelling of polymer properties. It seems certain that achieving even a portion of these goals would open up a completely new area of material science. Hence, following the model of DNA, we propose developing a number of new routes for the preparation of sequence controlled polymers (SCPs) and specifically a new class of SCPs which are capable of replication and ultimately evolution. This will produce polymers and self-assembled structures with unprecedented physical properties and the ability to functionally interact and communicate with biological materials. Realizing this goal will allow us to bring new function to chemistry, through expanding chemical space to access new precision polymers

Keywords: self-assembly,functional amino acids,nucleobases,compartmentalization,templating,sequence control
An artificial water-soluble photosystem by protein design (PS3)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Medical Biotechnology
Countries involved: Israel,United States
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-06-01
End date: 2019-05-31
Duration (months): 60.0
Total project cost (EUR): 1997944.0
EU funding (EUR): 1997944.0
Participants: 2
Project status: CLOSED

This project aims at producing a fully functional light energy conversion system that is inspired by, but does not necessarily mimic, the fundamental solar energy conversion unit of natural photosynthesis – the photosystem. This is a formidable challenge that can be met with thorough understanding of biological energy and electron transfer processes, and the growing capabilities of computational protein design. Here, this knowledge and capabilities will be further developed and utilized for the design and construction of multi-cofactor, multi-subunit protein complexes with photosystem functionality. These will be designed to efficiently capture light in the visible and near infrared range, exploit it for driving the oxidation of a molecular redox carrier at one end, and providing highly reducing electrons at the other end. Our general goal will be achieved by designing protein-cofactor complexes that will facilitate light-driven electron- and excitation energy-transfer that will make up the reaction center, and light harvesting modules, respectively. Constructing protein scaffolds that will assemble and organize arrays of multiple pigments, and chains of redox cofactors are significant challenges at the forefront of the field of protein de novo design, and current theories of biological energy and electron transfer. Success will set a new standard, well beyond the current state of the art, for our ability to use computational protein design methods for assembling functional protein-cofactor complexes. These can be used as benchmarks to test and validate the engineering principles of biological energy conversion systems, as well as new ideas about their evolution. Practically, it will open new and exciting technological possibilities for constructing artificial solar energy conversion systems from biological building blocks, which may enable their introduction into living systems and the construction of novel bioreactors for light driven fuel production.

Keywords: photosynthesis,alternative energy,solar energy conversion,protein design,electron transfer,light harvesting
Nanostructured Surfaces: Molecular Functionality on advanced sp2-bonded substrates (NANOSURFS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Physical and Analytical Chemical Sciences
Countries involved: Germany
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2020-03-31
Duration (months): 72.0
Total project cost (EUR): 1983841.0
EU funding (EUR): 1983841.0
Participants: 1
Project status: CLOSED

Inspired by the diverse functionalities of complex molecular building blocks evidenced in manifold life processes as transport of respiratory gases, metabolism or light harvesting, we aim for a comprehensive characterization and control of molecular properties in surface-based model systems. To fully exploit and tune molecular functionality on substrates, a paradigm shift away from conventional metal supports, which might drastically affect adsorbates, is mandatory. We propose to apply nanostructured boron nitride (BN) monolayers and sp2-heterostructures as templates for molecular units and architectures. As indicated by the fascinating nanomesh interface and the electronically corrugated atomically thin BN sheet on Cu we recently reported, inert, temperature stable and insulating BN has a huge potential as advanced substrate supporting molecular functionality, self-ordering and intercalation. By combining the inherent functionality of organic or bio-molecular building blocks with the unusual electronic and structural characteristics of advanced sp2-bonded substrates grown by chemical vapour deposition, we aim to achieve desired properties, including electronic, magnetic and conformational switching, tunable reactivity, or tailored electronic band gaps. Special emphasis will be put on economic substrates as thin films or foils, which open perspectives for scalable processing. With this proposal, we wish to establish research at the interface of surface science, supramolecular chemistry and materials engineering, yielding new insight into physicochemical processes at the single-molecule level, but also offering pathways to molecular sensors, switches, catalysts and devices, thus making a viable contribution to the on-going quest for innovation in nanotechnology. State-of-the-art scanning probe microscopy, a proposed new apparatus for the growth and handling of sp2-sheets and complementary X-ray based techniques will be used to tackle this ambitious project.
Deciphering the molecular language orchestrating host-microbiome interactions and their effects on health and disease (META-BIOME)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Immunity and Infection
Countries involved: Israel
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-03-01
End date: 2019-02-28
Duration (months): 60.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: CLOSED

The gastrointestinal tract hosts the microbiome, one of the highest microbial densities on earth. Diverse host-microbiome interactions influence a multitude of physiological and pathological processes, yet the basic mechanisms regulating host-microbiome interactions remain unknown. Deciphering the codes comprising the host-microbiome communication network and factors initiating loss of homeostasis (termed dysbiosis) will enable the recognition of pathways and signals critically important to initiation and progression of common immune and metabolic disorders. We recently identified the NLRP6 inflammasome as a critical innate immune regulator of colonic microbial ecology, with its disruption resulting in auto-inflammation and tumorigenesis. We will use this unique system, coupled with innovative robotic high-throughput modalities, gnotobiotics, metagenomics and multiple genetically altered mouse models to generalize our studies and decipher the critical principles governing host-microbiome interactions. We will elucidate the host-derived microbiome recognition signaling pathway at its entirety, from its upstream activators to the downstream effector molecules controlling microbial ecology; uncover the principles generating a stable microbiota composition; and develop and apply computational modelling to dissect the general mechanisms disrupting microbiome stability leading to dysbiosis. Using this innovative experimental and computational toolbox we will study the impact of dysbiosis on key components of the metabolic syndrome, and apply our findings to devise the first rational proof-of-concept approach for individualized microbiome-based treatment for these common disorders. At the basic science level, unraveling the principles of host-microbiota interactions will lead to a conceptual leap forward in our understanding of physiology and disease. Concomitantly, it may generate a platform for microbiome-based personalized therapy against common idiopathic illnesses.

Keywords: inflammasome,microbiome,metabolism,innate immunity,dysbiosis,disease pathogenesis,microbial ecology,metagenomics,gnotobiotics,mouse models,metabolic syndrome,infection,auto-inflammation
Spectroscopic Studies of N2 Reduction: From Biological to Heterogeneous Catalysis (N2RED)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Physical and Analytical Chemical Sciences
Countries involved: Germany,Germany
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2019-03-31
Duration (months): 60.0
Total project cost (EUR): 1989600.0
EU funding (EUR): 1989600.0
Participants: 2
Project status: CLOSED

The conversion of dinitrogen (N2) to ammonia (NH3) is of fundamental biological and economic importance. The catalytic conversion is achieved either industrially, using heterogeneous catalysts or biologically, by the nitrogenase enzyme. However, in both cases, the mechanistic details of the process are not fully understood. In order to design advance catalysts that will be essential for a sustainable energy economy, an in-depth understanding of both the biological and chemical mechanisms is required. The goal of this proposal is to develop advanced spectroscopic tools, which will allow for a detailed description of the atomic level processes in the both the biological and the heterogeneous systems. This will include the development of valence to core resonant X-ray emission spectroscopy as a unique probe of transition metal ligation in complex media. High-resolution X-ray absorption, X-ray emission, X-ray magnetic circular dichroism, and nuclear resonant vibrational spectroscopy will be utilized and their chemical information content fully developed. These experiments will be correlated to advanced quantum chemical calculations to obtain a detailed picture of the electronic structure of the catalytic systems. The results should provide a clear understanding of the electronic factors that govern N-N bond cleavage. The proposed research will bring together the fields of biochemistry and heterogeneous catalysis, by utilizing inorganic, physical and theoretical chemistry to advance our fundamental understanding of N2 cleavage. The proposed developments will provide a powerful set of novel tools for the elucidation of transition metal catalyzed homogenous and heterogeneous reaction mechanisms. The long-term goal is to pave the way for rationally designed catalytic systems, based on fundamental mechanistic knowledge.

Keywords: nitrogen reduction,xas,xes,nitrogenase,catalysis