Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : QuasarChronicles (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Universe sciences
Entité participante : Leiden University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2496073.75 €

How the first luminous sources reionized diffuse baryons in the intergalactic medium (IGM) is one of the most fundamental open questions in cosmology. The latest CMB constraints suggest reionization occurred at z ~ 7-8, within the realm of the highest redshift quasars known. The overarching impetus of this proposal is that Euclid's imminent discovery of scores of bright quasar beacons in a neutral universe, combined with the exquisite sensitivity of JWST, will enable a set of qualitatively new absorption spectroscopy experiments. Abundant neutral hydrogen in the IGM imprints a distinct damping wing signature on quasar spectra, which we will exploit to obtain the best constraints on the timing of reionization to date. These same spectra provide a glimpse of baryonic structure prior to reionization, which we will use to determine whether X-rays emitted by primeval black holes during cosmic dawn pre-heated the IGM, and constrain the properties of the underlying dark matter. The quasar's own ionizing radiation powers a cosmological-scale HII region encoding its radiative history, which we propose to map in absorption to answer the enigmatic question of how supermassive black holes grew to 10^9 M_sun just 800 Myr after the Big Bang. The same massive stars which reionized the IGM inevitably exploded in supernovae polluting the Universe with metals. These metals, if they reside in the neutral IGM, manifest as a forest of low-ionization absorbers, which we will use to constrain early IGM enrichment, and trace the history and topology of reionization with cosmic time. By conducting end-to-end analyses encompassing observations, theoretical modeling, state-of-the-art simulations, and Bayesian inference, we will elevate the quantitative study of reionization to be on the same solid methodological and statistical footing as other precision cosmological measurements. The PI is uniquely positioned to achieve these goals and has a proven track record for this type of synergy.

Mots-clés : the intergalactic medium,reionization,cosmic dawn,quasar absorption lines,the growth of supermassive black holes,cosmic enrichment
Projet ERC : bInDR (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

How transcription factors (TFs) bind rapidly at specific sites within large genomes remains a major mystery. Specificity is puzzling since TFs select a small fraction of their potential binding sites - short and highly abundant DNA motifs. Rapid detection of these selected sites is challenging due to the small motif size and the large number of non-specific sites within a genome. Despite extensive efforts, a unifying model accounting for these challenges, underlying the foundations of gene regulation, is still missing. Our recent results revealed an unexpected role of long intrinsically disordered regions (IDRs) in determining the in-vivo binding specificity of TFs. Long IDRs are ubiquitous among eukaryotic TFs, but their potential role is largely unknown. By studying two budding yeast TFs, we found that in-vivo binding specificity depends on long (>500 residues) IDRs located outside the DNA binding domains (DBDs). Furthermore, IDRs direct TF binding to the selected set of promoters using multiple weak specificity determinants distributed throughout their entire sequence. Our results suggest that TFs search for their binding sites through a two-tier process: Specificity determinants distributed within long IDRs direct TFs to broad promoter regions, allowing for subsequent localized search of the DBD for its short binding motif. We plan to establish this model by: (1) Defining the molecular basis of IDR-promoter recognition and its sequence recognition code, (2) Defining the dynamic profile of IDR-based DNA recognition, and (3) Elucidating the evolutionary implications of this novel recognition mode. Through a combination of experiments, computation and theory, carried out by an interdisciplinary group of students, our study will establish a new paradigm that explains the efficiency and specificity of the search of TFs for their in-vivo binding targets, providing a new solution for a long-standing mystery.

Mots-clés : transcription factor,in vivo binding specificity,budding yeast
Projet ERC : Unequal Lifespans (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Southern Denmark — Pays : Danemark — Rôle : PI
Acronyme de l'entité : SDU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 689012.5 €

How unequal are lifespans at older ages? How unequal will they be in the future? The length of life is often summarized by life expectancy, but the mean does not capture the spread. Distributions of lifespans need to be analyzed and forecast. Given the relevance of such research—for assessing pension reforms and other social and health policies—it is remarkable how little demographic modeling has been devoted to inequalities at older ages in individual lifespans. The research proposed here has three audacious ambitions and bold theoretical thrusts: (1) broaden discourse and conceptually shift thinking about retirement to include individual lifespan inequalities, (2) developing the demographic theory of old-age mortality, test the hypothesis that substantial progress is being made in cutting death rates after age 90, and (3) develop an innovative theory-based forecasting method based on 8 strong regularities of mortality trajectories at older ages that goes well beyond the state of the art to predict lifespan distributions (and inequalities)—and to quantify the uncertainties in these predictions. Preliminary research, mostly on Denmark but also some on Sweden, France and Japan, to prepare this application produced findings that surprised me. The probability of dying after age 50 but before retirement age was higher than I suspected. The likely growth in the number of people above age 90 astonished me. Rates of improvement in mortality after age 100 in France and Japan were much greater than published estimates for Denmark or Sweden. Current forecasting methods appear inadequate to capture likely reductions in death rates at the ages when most people die. These preliminary findings suggest that the daring theory-based, theory-building program of analysis of 40+ countries/regions proposed here will open new perspectives for research on lifespans at older ages as well as providing novel, highly-relevant input to discussions of the challenges of raising retirement ages.
Projet ERC : CHROMONUMBER (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Institut Curie — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1400276.02 €

How variations in whole chromosome number impact organism homeostasis remains an open question. Variations to the normal euploid genome content are frequently found in healthy animals and are thought to contribute with phenotypic variability in adverse situations. Yet they are also at the basis of several human diseases, including neuro-developmental disorders and cancer. Our preliminary data shows that physiological aneuploidy can be identified in certain cells during development. Moreover, we have observed that when induced through mutations, non-euploid cells are effectively eliminated from the cycling population. A quantitative view of the frequency of non-euploid karyotypes and the mechanisms underlying their genesis is lacking in the literature. Further, the tissue specific responses at play to eliminate non-euploid cells, when induced through mutations are not understood. The objectives of this proposal are to quantitatively assess the occurrence of physiological chromosome number variations gaining insight into mechanisms involved in generating it. Additionally, we will identify the tissue-specific pathways involved in maintaining organism homeostasis through the elimination of non-euploid cells. We will use a novel genetic approach to monitor individual chromosome loss at the level of the entire organism, combine it with quantitative methods and state-of-the art-microscopy, and focus on two model organisms - Drosophila and mouse - during development and adulthood. We predict that the findings resulting from this proposal will significantly impact the fields of cell, developmental and animal physiology, generating novel concepts that will bridge the existing gaps in the field, and expand our understanding of the links between karyotype variations, animal development and disease establishment.

Mots-clés : aneuploidy,polyploidy,cell death,premature differentiation,stem cells,epithelial cells,tissue dependent responses,microcephaly,cancer
Projet ERC : INCLUSION (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : European University Institute — Pays : Italie — Rôle : PI
Acronyme de l'entité : EUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1003000.0 €

Human migratory flows are currently at an unprecedented scale. The majority of these flows concern forced displacements, turning into long-term settlements in host countries, making ethnic diversity a permanent feature of our societies. Managed incorrectly, rapid changes in ethnic composition can harm host communities’ social capital and give ways to ethnic conflicts and polarization. Given that immigration will remain an inevitable global reality for the foreseeable future, designing and implementing inclusive social policies emerge as pressing policy imperatives. Leveraging the power of public education, the overarching goal of the proposed study program is to offer evidence-informed policy actions to help build ethnically diverse communities characterized by tolerance and inclusion rather than conflict and segregation. The proposal builds on a decade long research agenda to implement and test two uniquely designed educational interventions, one mitigative, the other preventative in nature. These interventions will involve two large-scale randomized controlled trials (RCTs) to be run in parallel for four consecutive years. The first study concerns a unique educational action to mitigate ethnic tensions and conflict in at-risk post-primary schools. The second study involves a pedagogical transformation intervention targeting primary school children who will progress into the post-primary schools targeted in the first study. Both RCTs are novel with respect to the content and delivery of the interventions, comprehensiveness of outcomes to be measured, sample size, and long-term follow-up opportunity. The results of this research program will: (i) generate much-needed evidence to design effective educational policies aiming at building social cohesion in communities afflicted by mass migratory flows, (ii) unravel for the first time the causal role of public education in raising tolerant and inclusive generations, free from ethnic conflict and segregation.

Mots-clés : social inclusion,inter ethnic cohesion,educational achievement,forced displacement,refugee integration
Projet ERC : TRECEPTORS (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1480180.0 €

Human solute carriers (hSLC) form a superfamily of integral membrane proteins that transport small molecules and ions across membranes, and their transport functions are essential to processes ranging from synaptic transmission to apoptosis. Moreover, some hSLCs are the cellular receptors of human and pathogenic proteins, and play important roles in organogenesis, as well as infectious diseases. The hSLC transport and receptor functions are involved in a wide range of pathological conditions, which makes them important emerging drug targets in cancer, psychiatric disorders, and infectious diseases. Despite their paramount importance in human physiology and pathology, the current understanding of hSLCs molecular mechanisms of function and pharmacology still relies extensively on prokaryotic homologs that serve as structural and molecular models. However, due to the evolutionary divergence of these homologs, they fall short of uncovering the complexity of the hSLCs’ architectures and molecular mechanisms. Here, we aim to unravel novel transport, receptor and pharmacological mechanisms of medically important hSLCs using a multidisciplinary biophysical approach. To achieve this, we will determine the high-resolution structures of hSLCs and their macromolecular complexes with other membrane, as well as soluble proteins. Moreover, we will complement and challenge the structural data with functional approaches to probe the proteins dynamics and thermodynamics, as well as computational approaches to aid in drug discovery. Our research will expand our current molecular knowledge on the hSLCs, and aid understanding their cellular functions, as well as, uncovering their tremendous pharmacological potential.

Mots-clés : human solute carriers,membrane protein structure,membrane protein dynamics,macromolecualr complexes,viral receptor,cell fusion,virus cell entry inhibitors,cancer therapy
Projet ERC : TRECEPTORS (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Institut Pasteur — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 569945.0 €

Human solute carriers (hSLC) form a superfamily of integral membrane proteins that transport small molecules and ions across membranes, and their transport functions are essential to processes ranging from synaptic transmission to apoptosis. Moreover, some hSLCs are the cellular receptors of human and pathogenic proteins, and play important roles in organogenesis, as well as infectious diseases. The hSLC transport and receptor functions are involved in a wide range of pathological conditions, which makes them important emerging drug targets in cancer, psychiatric disorders, and infectious diseases. Despite their paramount importance in human physiology and pathology, the current understanding of hSLCs molecular mechanisms of function and pharmacology still relies extensively on prokaryotic homologs that serve as structural and molecular models. However, due to the evolutionary divergence of these homologs, they fall short of uncovering the complexity of the hSLCs’ architectures and molecular mechanisms. Here, we aim to unravel novel transport, receptor and pharmacological mechanisms of medically important hSLCs using a multidisciplinary biophysical approach. To achieve this, we will determine the high-resolution structures of hSLCs and their macromolecular complexes with other membrane, as well as soluble proteins. Moreover, we will complement and challenge the structural data with functional approaches to probe the proteins dynamics and thermodynamics, as well as computational approaches to aid in drug discovery. Our research will expand our current molecular knowledge on the hSLCs, and aid understanding their cellular functions, as well as, uncovering their tremendous pharmacological potential.

Mots-clés : human solute carriers,membrane protein structure,membrane protein dynamics,macromolecualr complexes,viral receptor,cell fusion,virus cell entry inhibitors,cancer therapy
Projet ERC : INQMINDS (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of St Andrews — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Human technology is vastly superior to that of other apes: human tools from telescopes to the Large Hadron Collider exploit causal relationships but also explore them. What change over the brief course of hominid evolution made for such a big difference? One theory implicates a single cognitive distinction: the ability to reinterpret the world in abstract terms. In contrast, in several studies, chimpanzees seemed to rely on surface appearances, as if for the apes there was no more to the situation than met the eye. The theory is seductively simple, but this proposal argues that it is too early to rule out deep evolutionary roots for inquiring minds. Experiments designed specifically to compare humans and other primates are proposed covering two broad lines of study: causal cognition and executive function. To disentangle causal reasoning from simpler mechanisms three approaches are planned. The first will look at intervention: will subjects use exploration to seek hidden causes? The second will focus on natural mechanics: do subjects reason about physical properties or rely on perceptual correlates? The third examines causal learning from observation when the task’s mechanics are opaque. The second line of study explores executive functions. An inquiring primate mind could flourish if more information could be held in mind and manipulated. But we know little about how executive functions compare across primates. A new test battery will explore levels of working memory, inhibition, and attention shifting. Executive functions undergo radical development in human childhood, and individual differences correlate with performance on tests of physical and social reasoning. The intersection between these skills may therefore be particularly revealing. This proposal aims to use cross-sectional testing of causal cognition and executive control in the same individuals to explore how these cognitive skills interact to produce inquiring minds.

Mots-clés : cognition,causal learning,developmental psychology,comparative psychology,executive function
Projet ERC : CLAP (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : King Juan Carlos University — Pays : Espagne — Rôle : PI
Acronyme de l'entité : URJC
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 149701.0 €

Human-computer interaction (HCI) and Virtual reality (VR) are two fields that are succeeding to break from the research setting into the market. The CLAP project follows this trend and will introduce practical advances into both HCI and VR. In a nutshell, it will enable users to interact with digital content directly with their hands. CLAP is sustained on recent research carried out in the ERC Starting Grant 'Animetrics', which enables interactive simulation of natural hands. Thanks to the results in Animetrics, it is possible to see a high-quality virtual copy of the user's own hands in a virtual world, naturally interact with digital content, and create new interaction possibilities. The CLAP project will aid in the setup of a market-ready software solution, which can be embedded in third-party application-development environments (e.g., game development software), and coupled to hand-tracking hardware solutions. Developers will obtain in a seamless manner virtual hands which can be robustly coupled to other content. Prior to this proposal, we have verified market interest on the proposed software solution. Major global players in the software field are working on HCI/VR projects, including hand tracking. But they all miss solutions for natural hand simulation which allows applications with digital objects are naturally and intuitively manipulated. Our proposed solution could play a key role in future developments. A major action in the project will be to determine the best business model (i.e., b2b or b2c), and plan further development steps accordingly.

Mots-clés : virtual reality,human computer interaction
Projet ERC : EARTH@LTERNATIVES (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : University of Twente — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 462407.5 €

Humanity faces major challenges: stay below local and global ecological thresholds; increase natural resources use efficiency; share resources fairly; and increase societal resilience. Most research focusses on one or two of these challenges at a time; there is a major scientific gap in understanding synergies and inevitable trade-offs between the development principles of environmental sustainability, equitability, efficiency and resilience. This project aims to analyse synergies and trade-offs between environmental sustainability, resource efficiency, social equity and social-ecological resilience in the context of land and water use for food and energy supply. We consider production, consumption and trade patterns globally, at high spatial resolution, analyse past developments, and develop alternative future pathways, based on coherent sets of assumptions regarding demographic and economic developments, technological innovation, changes in local diets and energy mixes, and climate change. The project team will pioneer in integrating methods and computational tools from the fields of Environmental Footprint Assessment, Life Cycle Assessment and Input-Output Analysis, applied at unrivalled high level of granularity. Coherent perspectives on handling uncertainty and risk from cultural theory will be used in a unique approach to develop alternative futures. Finally, an original framework will be developed to analyse synergies and traded-offs between competing development principles. The project will revolutionize our understanding of different pathways to food and energy security given limited land and water resources, and particularly how each pathway will make trade-offs between environmental sustainability, fair sharing, efficient resources use and resiliency. This knowledge is key in understanding how to achieve UN’s Sustainable Development Goals with limited land and water resources and reveal synergies and trade-offs embedded in specific strategies.

Mots-clés : sustainability,resource use efficiency,equity,resilience,water land food energy nexus