Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : BioNet (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of London — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 531181.5 €

Enzymes created by Nature are still more selective and can be orders of magnitude more efficient than man-made catalysts, in spite of recent advances in the design of de novo catalysts and in enzyme redesign. The optimal engineering of either small molecular or of complex biological catalysts requires both (i) accurate quantitative computational methods capable of a priori assessing catalytic efficiency, and (ii) molecular design principles and corresponding algorithms to achieve, understand and control biomolecular catalytic function and mechanisms. Presently, the computational design of biocatalysts is challenging due to the need for accurate yet computationally-intensive quantum mechanical calculations of bond formation and cleavage, as well as to the requirement for proper statistical sampling over very many degrees of freedom. Pioneering enhanced sampling and analysis methods have been developed to address crucial challenges bridging the gap between the available simulation length and the biologically relevant timescales. However, biased simulations do not generally permit the direct calculation of kinetic information. Recently, I and others pioneered simulation tools that can enable not only accurate calculations of free energies, but also of the intrinsic molecular kinetics and the underlying reaction mechanisms as well. I propose to develop more robust, automatic, and system-tailored sampling algorithms that are optimal in each case. I will use our kinetics-based methods to develop a novel theoretical framework to address catalytic efficiency and to establish molecular design principles to key design problems for new bio-inspired nanocatalysts, and to identify and characterize small molecule modulators of enzyme activity. This is a highly interdisciplinary project that will enable fundamental advances in molecular simulations and will unveil the physical principles that will lead to design and control of catalysis with Nature-like efficiency.

Mots-clés : enhanced sampling alogrithms,free energy calculations,phosphate catalysis
Projet ERC : VITAL (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : PI
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499770.0 €

Epidemiological reports from around the world suggest that more people than ever before are living with (especially chronic) diseases. As a consequence, sustained efforts to reduce morbidity and mortality rates have been joined by systematised efforts to improve the lives – the quality of life – of those living with disease in ways that are measurable and auditable. VITAL will focus on the making of ‘quality of life’. While social studies of medicine have of late been marked by a ‘bio-turn’, it is apparent that within contemporary medicine, life is envisaged as much more than cellular and molecular activity; it is also a social activity and a personal experience. Not only is life sustained, it is also lived. In recent decades, morbid living – living with disease – has come to be the object of novel forms of knowledge, expertise, measurement and management while also generating new medical practices and attendant ways of relating to oneself. VITAL suggests a shift in attention from the ways in which the social sciences have previously studied morbid living and related issues of quality of life. Rather than continue longstanding efforts to understand how people cope with disease or to refine definitions and instruments for measuring the quality of life of the sick, in VITAL we will empirically study the co-production of ‘quality of life’ within healthcare through four ethnographically-grounded studies of how ‘quality of life’ is assembled, mobilised, negotiated and practiced in concrete medical settings. The four studies will focus on how knowledge about living with disease is assembled and mobilised, on the one hand, and how morbid living is negotiated and practiced on the other. The key outcomes of VITAL will be theoretical advancement of understandings of vitality in the 21st century beyond molecular biology and methodological innovation to facilitate empirical study of co-production processes that involve social science knowledge and practice.

Mots-clés : quality of life,medical anthropology
Projet ERC : EPICLINES (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Gregor Mendel Institute of Molecular Plant Biology — Pays : Autriche — Rôle : PI
Acronyme de l'entité : GMI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 2498468.0 €

Epigenetics continues to fascinate, especially the notion that it blurs the line between “nature and nurture” and could make Lamarckian adaptation via the inheritance of acquired characteristics possible. That this is in principle possible is clear: in the model plant Arabidopsis thaliana (Thale cress), experimentally induced DNA methylation variation can be inherited and affect important traits. The question is whether this is important in nature. Recent studies of A. thaliana have revealed a pattern of correlation between levels of methylation and climate variables that strongly suggests that methylation is important in adaptation. However, somewhat paradoxically, the experiments also showed that much of the variation for this epigenetic trait appears to have a genetic rather than an epigenetic basis. This suggest that epigenetics may indeed be important for adaptation, but as part of a genetic mechanism that is currently not understood. The goal of this project is to determine whether the global pattern of methylation has a genetic or an epigenetic basis, and to use this information to elucidate the ultimate basis for the global pattern of variation: natural selection.
Projet ERC : DECAF (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : TU Dortmund University — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1078828.49 €

Epigenetics plays a fundamental role in the function and regulation of the genome. From an evolutionary viewpoint, a pressing question is whether epigenetic modifications are a source of adaptive variation. To answer this question substantial attention is being given to the epigenetic marks themselves, but surprisingly little is known about the evolutionary underpinnings of the genomic sites that anchor them. Using novel analytical and technical approaches, I want to address this fundamental knowledge gap. I will use the best understood epigenetic mark, DNA methylation, as a model and advance on recent findings in avian genome evolution, epigenetic inheritance and sequencing technology. This will enable me to pinpoint signatures of epigenetically driven adaptation. I have designed separate approaches at three different levels: (1) At the individual level, to identify stably methylated anchors in the avian germline with focus on a recently discovered germline-specific chromosome, (2) at the population level, to establish the selective forces acting on DNA methylation diversity in natural populations and (3) at the species level, to gain insight into how fast-mutating anchors of DNA methylation act as potential facilitators of species differentiation and barriers. Ultimately, by combining these three levels I will be able to pinpoint epigenetic anchors that are involved in molecular adaptation. The possible research outcomes will not only be valuable to evolutionary biologists and ecologists, but will also make fundamental contributions to molecular biology and possibly medical research, and will deepen our understanding of how epigenetic marks manifest themselves at the sequence level.

Mots-clés : adaptive evolution,dna methylation,speciation,gene flow,mutation rate variation,embryogenesis,bird genomics,whole genome sequencing,epigenetics
Projet ERC : SleepEpisMemory (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2566250.0 €

Episodic memory is a core element of the human mind, but how experiencing an episode consolidates into long-term memory remains a central unsolved question in cognitive science. We will test the hypothesis that hippocampal-cortical dialogue (HCD) during sleep promotes memory consolidation, a hypothesis that has been largely beyond direct testing in humans to date. Moreover, transcending report is essential, since it remains unclear if sleep improves memory per-se, or the ability to access and report memories. Conventional paradigms do not facilitate sleep and memory research in dementia, where it is vital. Based on my expertise, ongoing studies, and preliminary results, I propose a unique approach to address these gaps by combining novel approaches to recording and stimulating brain activity in human sleep with novel ‘no-report’ memory paradigms. We will go beyond the state-of-the-art in three synergistic domains: (1) Develop an ecological ‘no-report’ paradigm to study episodic memory, and its consolidation during sleep. (2) Test the role of sleep HCD in mediating human memory consolidation. (3) In dementia and aging, we will investigate to what extent disrupted HCD during sleep impairs memory consolidation, and whether noninvasive neuromodulation can improve memory in dementia. The proposed research has the potential to elucidate fundamental principles and transform conceptual insights of how sleep promotes episodic memory consolidation.
Projet ERC : EPIMODKIT (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : German Cancer Research Center — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : DKFZ
Type d'entité : Recherche
Financement ERC de l'entité : 100000.0 €

Epitranscriptomic modifications constitute specific marks in mRNA that regulate gene expression. Identification of epitranscriptomic modifications requires next generation sequencing analyses and specific validation, processes that are cumbersome and time consuming. Furthermore, while some modifications are straightforward to identify, as they cause specific base changes (like RNA editing), most are only detectable either through chemical means (requiring large quantities of material) or by immunoprecipitation followed by sequencing. Of these techniques, immunoprecipitation requires far less material and can be used in any molecular biology laboratory, but depends exquisitely on the quality of the monoclonal antibodies that recognize the modification - their specificity, selectivity and sensitivity. Most anti-modification antibodies are generated using traditional methods for the production of monoclonals to small molecule haptens (e.g. conjugation to a large protein carrier and injection into animals together with an adjuvant). While these methods can generate anti-hapten responses with some specificity they are generally not very selective. We have developed a novel immunization platform that exquisitely focuses the antibody response to a hapten to generate high affinity monoclonals with a high degree of specificity. We propose to employ this approach to generate anti-inosine antibodies (for the detection of editing in disease contexts); anti-m6A antibodies (which would be benchmarked against the ones currently in use, validating our approach); and antipseudo-uridine antibodies (a tool that is lacking in the field and for which traditional approaches have completely failed). The generation of specific and selective antibodies to these three modifications, will open the way toward a better understanding of their intricate molecular roles in biological proceGenerating monoclonal antibodies that selectively and specifically recognize epitranscriptomic modifications.

Mots-clés : rna editing,rna modification,epitranscriptomic modifications,anti modification antibodies
Projet ERC : RESPICHAIN (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Institute of Science and Technology Austria — Pays : Autriche — Rôle : PI
Acronyme de l'entité : ISTA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1781133.0 €

Eukaryotic life is made possible by energy production in mitochondria, where several large membrane protein complexes of the respiratory chain work in series to produce ATP. The structure and function of these complexes have been intensively studied over decades, but the mechanistic understanding is lacking due to their elaborate architecture. This proposal’s goal is to reveal the mechanism of energy transduction by the least understood of them: complex I, respiratory supercomplexes and transhydrogenase. Complex I is the largest respiratory enzyme, containing up to 45 subunits with a total mass of ~1 MDa. We have determined the first atomic structures of complex I from bacteria and mitochondria. Mammalian complex I usually exists as a supercomplex with complexes III2 and IV: we have determined the first architecture of this ~1.7 MDa physiological “unit” of respiration. The nicotinamide nucleotide transhydrogenase couples proton motive force to mitochondrial redox homeostasis, working in tandem with the respiratory chain. We recently determined the first structure of transhydrogenase but its coupling mechanism remains controversial. Huge conformational changes are envisaged but not yet observed. The mechanism of coupling between spatially separated electron transfer and proton translocation in complex I is also a mystery. It is likewise not known why respiratory complexes are organised into supercomplexes. We will tackle all these questions by an integrative approach, solving the atomic structures of different catalytic states of the complexes by applying the latest cryo-EM methods to these extremely challenging targets. The comparison of structures, complemented by functional and computational analyses, will reveal the mechanistic basis for the function of these molecular machines, solving fundamental questions in biology. As these enzymes are involved in many severe human disorders, the acquired knowledge will also be instrumental to tackle mitochondrial diseases.

Mots-clés : membrane protein structure,respiratory chain,mitochondria,nadh ubiquinone oxidoreductase,complex i,cryo em,redox protein,respiratory supercomplexes,proton translocating transhydrogenase
Projet ERC : ArtEmpire (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Universidad Pablo de Olavide — Pays : Espagne — Rôle : PI
Acronyme de l'entité : UPO
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1264528.64 €

European incursions onto the narrow isthmian pass that divided and connected the Atlantic and Pacific oceans made it a strategic node of the Spanish Empire and a crucial site for early modern globalization. On the front lines of the convergence of four continents, Old Panama offers an unusual opportunity for examining the diverse, often asymmetrical impacts of cultural and commercial contacts. The role of Italian, Portuguese, British, Dutch, and French interests in the area, as well as an influx of African slaves and Asian merchandise, have left a unique material legacy that requires an integrated, interdisciplinary approach to its varied sources. Bones, teeth and artifacts on this artery of Empire offer the possibility of new insights into the cultural and biological impact of early globalization. They also invite an interdisciplinary approach to different groups’ tactics for survival, including possible dietary changes, and the pursuit of profit. Such strategies may have led the diverse peoples inhabiting this junction, from indigenous allies to African and Asian bandits to European corsairs, to develop and to favor local production and Pacific trade networks at the expense of commerce with the metropolis. This project applies historical, archaeological and archaeometric methodologies to evidence of encounters between peoples and goods from Europe, America, Africa and Asia that took place on the Isthmus of Panama during the sixteenth and seventeenth centuries. Forging an interdisciplinary approach to early globalization, it challenges both Euro-centric and Hispano-phobic interpretations of the impact of the conquest of America, traditionally seen as a demographic catastrophe that reached its nadir in the so-called seventeenth-century crisis. Rather than applying quantitative methods to incomplete source material, researchers will adopt a contextualized, inter-disciplinary, qualitative approach to diverse agents involved in cultural and commercial exchange.

Mots-clés : conquest,commerce,cultural exchange,global history,globalization
Projet ERC : ArtEmpire (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The study of the human past
Entité participante : Curt Engelhorn Centre Archaeometry — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : CEZA
Type d'entité : Recherche
Financement ERC de l'entité : 176346.36 €

European incursions onto the narrow isthmian pass that divided and connected the Atlantic and Pacific oceans made it a strategic node of the Spanish Empire and a crucial site for early modern globalization. On the front lines of the convergence of four continents, Old Panama offers an unusual opportunity for examining the diverse, often asymmetrical impacts of cultural and commercial contacts. The role of Italian, Portuguese, British, Dutch, and French interests in the area, as well as an influx of African slaves and Asian merchandise, have left a unique material legacy that requires an integrated, interdisciplinary approach to its varied sources. Bones, teeth and artifacts on this artery of Empire offer the possibility of new insights into the cultural and biological impact of early globalization. They also invite an interdisciplinary approach to different groups’ tactics for survival, including possible dietary changes, and the pursuit of profit. Such strategies may have led the diverse peoples inhabiting this junction, from indigenous allies to African and Asian bandits to European corsairs, to develop and to favor local production and Pacific trade networks at the expense of commerce with the metropolis. This project applies historical, archaeological and archaeometric methodologies to evidence of encounters between peoples and goods from Europe, America, Africa and Asia that took place on the Isthmus of Panama during the sixteenth and seventeenth centuries. Forging an interdisciplinary approach to early globalization, it challenges both Euro-centric and Hispano-phobic interpretations of the impact of the conquest of America, traditionally seen as a demographic catastrophe that reached its nadir in the so-called seventeenth-century crisis. Rather than applying quantitative methods to incomplete source material, researchers will adopt a contextualized, inter-disciplinary, qualitative approach to diverse agents involved in cultural and commercial exchange.

Mots-clés : conquest,commerce,cultural exchange,global history,globalization
Projet ERC : EXPLO (Horizon 2020, appel 2018, Synergy grants)
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1141831.0 €

European societies today face unprecedented environmental change. Understanding how human societies responded to past challenges of environmental change relates to the interface between culture and environment. The EXPLO project proposes a novel interdisciplinary approach to investigate key questions regarding the interaction between past human ways of life, land use and the wider environment through a unique combination of archaeological, biological and dynamic mathematical modelling approaches. Archaeological prehistoric sites in lakes of northern Greece and the southern Balkans provide an excellent opportunity to investigate rich archives of societal and environmental change in the cradle of European farming. Natural lake sediments and submerged prehistoric settlements offer exceptional preservation conditions and uniquely holistic insights into past anthroposphere, biosphere and geosphere dynamics. More than 8,000 years ago, technological and social breakthroughs allowed the introduction of farming from western Asia to Greece and thus for the first time to Europe; however, so far there is no high-resolution picture of how this revolutionary innovation interacted with the environment, including its long-term consequences. New underwater archaeological research will allow the construction of highly precise settlement chronologies on the basis of dendrochronology, radiocarbon dating and Bayesian modelling. On-site information from excavations will be combined with off-site palaeoenvironmental data from the same lakes to investigate past adaptation strategies to the environment as well as the effects of past societies on their environments. Dynamic models integrating archaeological contexts and palaeoenvironmental data will open up the opportunity to investigate vulnerability, resilience, tipping points and thresholds of ancient agrarian economies, with implications for future food systems under a rapidly changing climate.

Mots-clés : neolithic,bronze age,paleoecology,bioarchaeology,balkans,northern greece,wetlands,underwater archaeology,early agropastoral societies,lande use,anthropogenic land cover land use change