Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : EXTREME (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3498825.0 €

The mechanical properties of structural animal tissues like bone, tendon and skin are determined by the extracellular matrix (ECM) of the tissue, a complex, changeable 3D material that forms a scaffold around the tissue’s cells. The matrix is under constant mechanical stress from our everyday movements. When it is damaged, cells in the tissue repair it; where there is repeated damage, cells must strengthen the matrix, not just repair. Thus, drivers of cell behaviour are encoded into the detailed molecular structure of the ECM. For cells to respond appropriately when they re-structure the ECM – simple repair or strengthen, for example – they need access to its mechanical history. However, there is currently little understanding of how the mechanical history of the ECM is encoded into its molecular structure. New work shows that chemistry happens in the ECM under mechanical strains. Covalent bonds break resulting in chemical modifications to extracellular proteins, the modifications depending on the strain. This suggests Nature has evolved an exquisite mechanism to communicate the mechanical history of the ECM to cells, using mechanochemistry resulting from the forces on the tissues to accumulate specific molecular cues into the ECM. The challenge now is to determine what these ECM mechanochemical modifications are, how cells use them and how they change in ageing and diseases such as diabetes and cancer. There are few methods to probe atomic structures in highly heterogeneous materials such as the ECM. I have developed solid-state NMR (SSNMR) methodology over the last 15 years to determine molecular structure changes and follow chemistry in the ECM. Here, I will develop an SSNMR approach to determine the chemical modifications to the ECM of intact tissues under mechanical deformations. I will use the new methodology to develop important new insight into how cells interpret their environment that will impact on how we understand human diseases and ageing.

Mots-clés : collagen,extracellular matrix,tissue mechanics
Projet ERC : ACTOMYOSIN RING (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Warwick — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2863705.0 €

The mechanism of cell division is conserved in many eukaryotes, from yeast to man. A contractile ring of filamentous actin and myosin II motors generates the force to bisect a mother cell into two daughters. The actomyosin ring is among the most complex cellular machines, comprising over 150 proteins. Understanding how these proteins organize themselves into a functional ring with appropriate contractile properties remains one of the great challenges in cell biology. Efforts to generate a comprehensive understanding of the mechanism of actomyosin ring assembly have been hampered by the lack of structural information on the arrangement of actin, myosin II, and actin modulators in the ring in its native state. Fundamental questions such as how actin filaments are assembled and organized into a ring remain actively debated. This project will investigate key issues pertaining to cytokinesis in the fission yeast Schizosaccharomyces pombe, which divides employing an actomyosin based contractile ring, using the methods of genetics, biochemistry, cellular imaging, DNA origami, genetic code expansion, and click chemistry. Specifically, we will (1) attempt to visualize actin filament assembly in live cells expressing fluorescent actin generated through synthetic biological approaches, including genetic code expansion and click chemistry (2) decipher actin filament polarity in the actomyosin ring using total internal reflection fluorescence microscopy of labelled dimeric and multimeric myosins V and VI generated through DNA origami approaches (3) address when, where, and how actin filaments for cytokinesis are assembled and organized into a ring and (4) reconstitute actin filament and functional actomyosin ring assembly in permeabilized spheroplasts and in supported bilayers. Success in the project will provide major insight into the mechanism of actomyosin ring assembly and illuminate principles behind cytoskeletal self-organization.

Mots-clés : cytokinesis,actomyosin ring,yeast,click chemistry,dna origami,genetic code expansion
Projet ERC : Homo.symbiosus (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Institut national de recherche pour l'agriculture, l'alimentation et l'environnement — Pays : France — Rôle : PI
Acronyme de l'entité : Inrae
Type d'entité : Recherche
Financement ERC de l'entité : 2291014.0 €

The microbiomics revolution has favoured the recognition of the gut as a true organ and the importance of man-microbes symbiosis in health and disease. Derived from a long co-evolution the latter has been challenged by numerous environmental triggers, modern lifestyles, changes in birth modalities, nutritional transition and therapeutic attitudes. A large fraction of the human population has tentatively entered a man-microbes dysbiotic state characterized by altered interactions between microbiome and host features with auto-aggravating crosstalk signals. The result is increased incidence of incurable immune-mediated diseases of modern societies that affect a third the human population on earth today and for which current therapeutics only address symptoms alleviation, rather than considering man as a holobiont. In this context and its resulting threat for the human species, I will carry out a project geared to open a new era of individualized preventive care and novel gut ecology-based therapeutic approaches. The project will assemble insights and contributions from theoretical to experimental ecology, quantitative and functional microbiomics, preclinical work, cohort studies and clinical trials, so as to: • Validate the concept of critical transition and alternative stable state as it applies to a shift from man-microbes symbiosis to disease-prone man-microbes dysbiosis • Assess the potential of diet alone to promote such a shift • Model the symbiosis-to-dysbiosis transitions and derive predictors of tipping points • Propose counter-measures that may allow to break vicious circles and restore a balanced, health-prone, man-microbes symbiosis by concomitantly acting upon microbiome and host features • Validate strategies to reinforce ecological robustness and restore man-microbes symbiosis Based on a paradigm shift, the proposed work will set the grounds for future personalized preventive nutrition and clinical management considering man as a true holobiont.

Mots-clés : intestinal ecology,host microbiota symbiosis,critical transition,dysbiosis,microbiotherapy
Projet ERC : SOFTBREAK (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Wageningen University & Research — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : WUR
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

The microscopic mechanisms that lead to mechanical failure of soft polymer materials are still poorly understood. The main reason for this is a lack of experimental tools to prepare well-controlled model systems and to observe the failure process in real time at the microscopic scale. Here, I propose to fill this gap by taking a multidisciplinary approach that combines innovative chemical tools with state-of-the art physical experiments and modelling. Previous work in my group has led to the development of polymer networks with extremely well-controlled architecture and bond strength, and of various tools to study their structure and mechanics. Here, I will take advantage of this expertise to systematically unravel the microscopic physics of failure of polymer networks. To visualize how the failure process proceeds, we will make use of recently developed mechanosensors, molecules that change colour in response to a force or that emit light when they break. These chemical tools will allow us to map in real time the spatial distribution of both strains and bond rupture events. Together with computer simulations carried out in parallel, this will give us unprecedented insight in the microscopic processes that occur during failure of the material, from the very first bonds that rupture, to the gradual accumulation of damage, all the way to macroscopic failure. We will use this to address the following unresolved questions about failure of polymer networks: 1. What is the microscopic mechanism that leads to delayed failure of polymer networks at subcritical loads? 2. How does the initiation of failure depend on the material's heterogeneity? 3. How does failure occur in a network with transient (viscoelastic) bonds? The project will not only provide detailed insight in the physics of failure of polymer networks, but it will also shed light on fracture physics in general. Finally, it will help material scientists to design new materials with superior properties.

Mots-clés : fracture,polymer networks
Projet ERC : SMART-DNA (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Potsdam — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UP
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1996476.0 €

The monitoring of single molecule reactions promises unrivalled insight into chemical reaction mechanisms, but represents one of the most challenging tasks in chemistry. Surface-enhanced Raman scattering (SERS) is a particularly attractive single molecule (SM) technique due to its high chemical specificity, which allows to directly detect relevant intermediates and molecular subpopulations. However, SM-SERS is still at a premature state due to the highly challenging task to place single molecules precisely in nanoscale gaps of plasmonic nanostructures. These are required to provide sufficiently high electromagnetic field enhancement to reach SM sensitivity. The aim of SMART-DNA is to exploit artificial DNA nanostructures to provide sufficient structural control to assemble both, nanoparticles and target molecules, with nanometer precision. By means of novel DNA origami nanostructures the distance between two nanoparticles will be controlled, and at the same time target molecules will be placed at the positions of highest Raman enhancement through DNA aptamers. Apart from Raman enhancement the excitation of the localized surface plasmon resonance of the metallic nanostructures results in other plasmonic effects such as heating and possibly the transfer of hot electrons. This can lead to diffusion, conformational changes or even dissociation of the target molecules. These issues do not only concern SM-SERS, but also make quantitative SERS and the SERS analysis of complex (bio)molecules very challenging. By the improved structural control achieved by SMART-DNA, nanoscale heating and hot electron transfer and their effect on SERS spectra will be studied on an ensemble and a SM level. Finally, reactions induced by plasmonically generated electrons in DNA and DNA modified with electrophilic molecules will be studied by SERS with the aim to develop novel strategies to improve cancer radiation therapies such as the photothermal therapy.

Mots-clés : surface enhanced raman scattering,dna origami,low energy electrons
Projet ERC : BinGraSp (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Friedrich Schiller University Jena — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : FSU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1432301.0 €

The most energetic electromagnetic phenomena in the Universe are believed to be powered by the collision of two neutron stars, the smallest and densest stars on which surface gravity is about 2 billion times stronger than gravity on Earth. However, a definitive identification of neutron star mergers as central engines for short-gamma-ray bursts and kilonovae transients is possible only by direct gravitational-wave observations. The latter provide us with unique information on neutron stars' masses, radii, and spins, including the possibility to set the strongest observational constraints on the unknown equation-of-state of matter at supranuclear densities. Neutron stars binary mergers are among the main targets for ground-based gravitational-wave interferometers like Advanced LIGO and Virgo, which start operations this year. The astrophysical data analysis of the signals emitted by these sources requires the availability of accurate waveform models, which are missing to date. Hence, the theoretical understanding of the gravitational spectrum is a necessary and urgent step for the development of a gravitational-based astrophysics in the next years. This project aims at developing, for the first time, a precise theoretical model for the complete gravitational spectrum of neutron star binaries, including the merger and postmerger stages of the coalescence process. Building on the PI's unique expertise and track record, the proposed research exploits synergy between analytical and numerical methods in General Relativity. Results from state of the art nonlinear 3D numerical relativity simulations will be combined with the most advanced analytical framework for the relativistic two-body problem. The model developed here will be used in the first gravitational-wave observations and will dramatically impact multimessenger astrophysics.

Mots-clés : gravitational waves,numerical relativity,binary neutron stars
Projet ERC : CROSSROADS (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : University of Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999250.0 €

The most important open questions in European paleoanthropology concern the timing, number and origin of early human dispersals into the continent, the identity and number of taxa present, and their possible interactions. These issues remain unresolved partly due to the lack of research in South-East Europe, a region at the crossroads between continents and a refugium for fauna, flora and possibly human populations during glacial times. The PI’s previous work there (ERC StG PaGE) aimed to add new evidence to further our understanding of human evolution on the continent. PaGE led to the discovery of several new Paleolithic sites, including the oldest radiometrically dated archaeological site from South-East Europe, placing the region squarely in the Paleolithic map of Europe. CROSSROADS is an ambitious, groundbreaking research program that builds on the foundation of PaGE to take Paleolithic research in the region to a new level. In contrast to the exploratory goals of PaGE, it focuses on the early part of the Paleolithic targeting the following questions: Can human presence in South-East Europe, considered a major dispersal route into the continent from Africa and the Near East, be documented beyond the current known chronology of ca. 500 ka BP, as shown in the West? Is there a gap between the earliest human arrival and subsequent human activity in the region, or was human habitation continuous, as would be expected in a refugium? What was the environmental backdrop of the early human dispersal and subsequent evolution? How did behavioral / biological change correlate with environmental changes, chronology and landscape use? Can we document a higher level of diversity in the human fossil record of the region than would be expected under evolutionary scenarios developed on Western European evidence, suggesting that different evolutionary processes were at work? The answers to these questions will be essential for testing hypotheses about human evolution in Eurasia.

Mots-clés : human evolution,early human dispersal,south east europe
Projet ERC : Myelination (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1392195.02 €

The myelin sheath is a plasma membrane extension that is laid down in regular spaced segments along axons of the nervous system. In the central nervous system it is formed by oligodendrocytes that spirally wrap their plasma membrane around axons to generate a highly abundant, tightly packed stack of membranes with unique structural properties. Previously, myelin has been regarded as an inert and purely insulating membrane, but it now appears that myelin is metabolically active, providing metabolic support to the underlying axon and participating in information processing by modulating velocity and synchronicity of nerve impulses in neuronal networks. In addition, myelination is not limited to the period of early post-natal development, but continuous into adulthood where it appears to be regulated by neuronal stimuli. This paradigm shift should be fuelled by new knowledge about myelin biology. Here, we plan to fill this gap by addressing the molecular basis of myelin growth, plasticity and remodelling. We will determine the factors that determine whether and to what extent an axon will be myelinated or not, the forces that drive myelin around the axon, the structural basis of myelin plasticity and the mechanisms of myelin turnover in the adult. We will test the hypothesis that microglia actively participate in myelin turnover by taking up myelin fragments that pinch off from the myelin sheath. To realize these aims we plan to pursue an integrative and multidisciplinary approach by bringing together genetics, biochemistry, proteomics and imaging in various model systems. The innovation arises from the combination of high-resolution imaging with molecular approaches in different cell types to obtain a unifying mechanistic understanding of myelin formation, maintenance and degradation. If successful, the project would not only explain how myelin is generated during brain development, but also give insight into how myelin plasticity could fine-tune neuronal networks.

Mots-clés : myelin,glia,oligodendrocytes,axons,membranes
Projet ERC : MyeRIBO (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of Santiago de Compostela — Pays : Espagne — Rôle : PI
Acronyme de l'entité : USC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1860519.27 €

The myelin sheath is essential for neuronal function and health: myelinating glial cells speed up propagation of axonal potentials, fuel the energetic demands and regulate the ionic environment of neurons. Lesions to the myelin sheath thus result in devastating neurological disorders that include multiple sclerosis, diabetic neuropathy and Charcot-Marie-Tooth disease. Myelination involves a striking expansion of the glial cell membrane that relies on an exceptional increase in protein and lipid synthesis rates. Decades of dedicated research has uncovered a complex transcriptional program that drives this process, whereas translational control mechanisms, on the other hand, have received little attention. There is emerging evidence, enabled by modern techniques, that ribosomes, typically viewed as invariant, passive molecular machines, may instead be heterogeneous in composition, with particular ribosomal components having a ‘specialized’ regulatory capacity for preferential translation of specific mRNAs. In MyeRIBO, I propose that translation control by specialized ribosomes is a novel layer of regulation that shapes the proteome of the myelinating glial cell. I will exploit advances in cryo-EM and quantitative proteomics analyses to discover the nature and diversity of ribosomes in myelinating cells, employ genome-wide ribosome profiling to obtain mechanistic insights into selective mRNA translation by heterogeneous ribosomes, and generate genetic mouse models to determine the functional consequences of this specialization for myelination in vivo. Notably, I will study the implication of this mechanism in pathogenesis of injury-induced demyelination and diabetic neuropathy, and evaluate the targeting of specialized ribosomal components as a preclinical strategy. MyeRIBO will push further the boundaries of our current understanding of the molecular control of myelination, which could have a profound impact for understanding neural development and myelin disorders.

Mots-clés : myelin,schwann cells,translation control,specialised ribosomes
Projet ERC : LHCtoLISA (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Deutsches Elektronen-Synchrotron DESY — Pays : Allemagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1975000.0 €

The nascent field of gravitational wave (GW) science will be an interdisciplinary subject, enriching different branches of physics, yet the associated computational challenges are enormous. Faithful theoretical templates are a compulsory ingredient for successful data analysis and reliable physical interpretation of the signals. This is critical, for instance, to study the equation of state of neutron stars, the nature of black holes, and binary formation channels. However, while current templates for compact binary sources may be sufficient for detection and crude parameter estimation, they are too coarse for precision physics with GW data. We then find ourselves in a situation in which, for key processes within empirical reach, theoretical uncertainties may dominate. To move forward, profiting the most from GW observations, more accurate waveforms will be needed. I have played a pioneering role in the development and implementation of a new formalism, known as the ‘effective field theory approach’, which has been instrumental for the construction of the state-of-the-art GW template bank. The goal of my proposal is thus to redefine the frontiers of analytic understanding in gravity through the effective field theory framework. Even more ambitiously, to go beyond the current computational paradigm with powerful tools which have been crucial for `new-physics' searches at the Large Hadron Collider. The impact of the high-accuracy calculations I propose to undertake will be immense: from probes of dynamical spacetime and strongly interacting matter, to the potential to discover exotic compact objects and ultra-light particles in nature. Furthermore, GW observations scan gravity in a regime which is otherwise unexplored. Consequently, the coming decade will tell whether Einstein's theory withstands precision scrutiny. In summary, my program will provide novel techniques and key results that will enable foundational investigations in physics through GW precision data.

Mots-clés : post newtonian theory,effective field theory,gravitational waves