Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : DismantlingNoise (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 1997853.0 €

Current estimates place the prevalence of obesity beyond 1 billion by the year 2030. As a critical risk factor for heart disease, diabetes and stroke, obesity represents one of the chief socio-economic challenges of our day. While studies have mapped a genetic framework for understanding obesity, the etiological contribution of several regulatory layers, and in particular epigenetic regulation, remain poorly understood. A perfect example, we know that isogenic C57Bl6/J mice can vary by as much as 100% in body weight upon high fat feeding; currently, we have no mechanistic explanation for the emergence of such phenotypic variation. Here, I propose three aims dedicated towards understanding the (epi)genetic control of phenotypic variation and disease susceptibility. First, we will catalogue epigenome and phenome variation to an unprecedented depth and resolution in the isogenic context. Next, we will examine two completely novel models of epigenetically sensitized bi-stable obesity and thus begin a mechanistic dissection of phenotypic variation. Finally, we will map a series of gene-gene and gene-environment epistasis interactions including eight models of developmental plasticity and approximately a dozen chromatin regulator mutants. The latter epistasis matrix will identify the molecular mechanisms that trigger, amplify and buffer phenotypic variation and stochastic obesity in mice. The functional (epi)phenomics approach is unique. It builds the first unbiased framework against which to understand developmental plasticity and phenotypic variation, and at the same time generates powerful resources for disease researchers worldwide.

Mots-clés : stochastic disease,stochastic obesity,phenotypic variation,chromatin,suvar,h3k9me3,epigenomics,phenome
Projet ERC : AMPLIFY (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : University of Stuttgart — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 657500.0 €

Current technical sensor systems offer capabilities that are superior to human perception. Cameras can capture a spectrum that is wider than visible light, high-speed cameras can show movements that are invisible to the human eye, and directional microphones can pick up sounds at long distances. The vision of this project is to lay a foundation for the creation of digital technologies that provide novel sensory experiences and new perceptual capabilities for humans that are natural and intuitive to use. In a first step, the project will assess the feasibility of creating artificial human senses that provide new perceptual channels to the human mind, without increasing the experienced cognitive load. A particular focus is on creating intuitive and natural control mechanisms for amplified senses using eye gaze, muscle activity, and brain signals. Through the creation of a prototype that provides mildly unpleasant stimulations in response to perceived information, the feasibility of implementing an artificial reflex will be experimentally explored. The project will quantify the effectiveness of new senses and artificial perceptual aids compared to the baseline of unaugmented perception. The overall objective is to systematically research, explore, and model new means for increasing the human intake of information in order to lay the foundation for new and improved human senses enabled through digital technologies and to enable artificial reflexes. The ground-breaking contributions of this project are (1) to demonstrate the feasibility of reliably implementing amplified senses and new perceptual capabilities, (2) to prove the possibility of creating an artificial reflex, (3) to provide an example implementation of amplified cognition that is empirically validated, and (4) to develop models, concepts, components, and platforms that will enable and ease the creation of interactive systems that measurably increase human perceptual capabilities.

Mots-clés : user experience,augmented senses,user interface technologies
Projet ERC : ACTOMYO (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : University of Porto — Pays : Portugal — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1499988.75 €

Cytokinesis completes cell division by partitioning the contents of the mother cell to the two daughter cells. This process is accomplished through the assembly and constriction of a contractile ring, a complex actomyosin network that remains poorly understood on the molecular level. Research in cytokinesis has overwhelmingly focused on signaling mechanisms that dictate when and where the contractile ring is assembled. By contrast, the research I propose here addresses fundamental questions about the structural and functional properties of the contractile ring itself. We will use the nematode C. elegans to exploit the power of quantitative live imaging assays in an experimentally tractable metazoan organism. The early C. elegans embryo is uniquely suited to the study of the contractile ring, as cells dividing perpendicularly to the imaging plane provide a full end-on view of the contractile ring throughout constriction. This greatly facilitates accurate measurements of constriction kinetics, ring width and thickness, and levels as well as dynamics of fluorescently-tagged contractile ring components. Combining image-based assays with powerful molecular replacement technology for structure-function studies, we will 1) determine the contribution of branched and non-branched actin filament populations to contractile ring formation; 2) explore its ultra-structural organization in collaboration with a world expert in electron microcopy; 3) investigate how the contractile ring network is dynamically remodeled during constriction with the help of a novel laser microsurgery assay that has uncovered a remarkably robust ring repair mechanism; and 4) use a targeted RNAi screen and phenotype profiling to identify new components of actomyosin contractile networks. The results from this interdisciplinary project will significantly enhance our mechanistic understanding of cytokinesis and other cellular processes that involve actomyosin-based contractility.

Mots-clés : cytokinesis,c  elegans,actin,myosin,formin,laser microsurgery
Projet ERC : CyPod (Horizon 2020, appel 2015, Proof of concept grants)
Entité participante : University of Twente — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Cytometry (the characterisation and counting of cells) is essential to clinical diagnostics, biotechnology, food industry, water monitoring and many fields of research. Within the ERC Starting Grant, InstantCount, inkjet printing methods have been developed, which allow us to fabricate cell counting chambers with on-chip sample preparation, simplifying cell counting procedures tremendously. By effectively eliminating all sample preparation steps and efficient usage of reagents CyPod promises low-cost, simple, rapid cell counting, including mobile applications. The fabrication by inkjet printing enables us to offer tailor-made solutions. We expect that CyPod tests can replace expensive and complex instruments in many existing cell counting applications, as well as open new markets, e.g. in agriculture and food industry. This project aims at evaluating and enhancing the competitiveness of CyPod cell counting technology by analysing the market, comparing CyPod with potential competitors and adapting our concept to identified customers’ needs. A product demonstration for potential customers and partners will be prepared and the optimal business strategy will be selected for which a business plan will be devised.

Mots-clés : cytometry,inkjet printing,microfluidics
Projet ERC : DEEP TIME (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
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 : 92626.36 €

DEEP TIME will unearth a record of geological time that is buried thousands of kilometres deep. The seafloor that covers two-thirds of the earth's surface is a tiny fraction of all seafloor created during its history – the rest has sunk back into the viscous mantle. Slabs of subducted seafloor carry a record of surface history: how continents and oceans were configured over time and where their tectonic plate boundaries lay. DEEP TIME will follow former surface oceans as far back in time as the convecting mantle system will permit, by imaging subducted slabs down to the core with cutting-edge seismological techniques. Current tectonic plate reconstructions incorporate little if any of this deep structural information, which probably reaches back 300+ million years; they are based on present-day seafloor, which constrains only the past 100-150 million years. DEEP TIME will match deep slab structure to the geological surface record of subduction – volcanic arcs and other crustal slivers that stayed afloat, survived collisions, and form the world’s largest mountain belts. Integrating these two direct records of subduction, the project will * Add paleo-trenches to existing plate reconstructions and extend them 2-3 times longer into the past. * Produce a 3-D atlas of the mantle that matches subducted seafloor with paleo-oceans inferred by land geology. * Rigorously test the hypothesis of vertical slab sinking, which may yield an absolute mantle reference frame. Tomographic models and geological land records will be synthesized into quantitative and testable paleogeographic reconstructions that complement and extend existing ones, especially in paleo-oceanic areas. This is likely to transform our understanding of the earth’s physical surface environment and biosphere during Mesozoic times, as well as the formation of natural resources. It also will put observational constraints on elusive mantle rheologies. Nearly every subdiscipline of the earth sciences could benefit.

Mots-clés : mantle structure,seismic tomography,plate tectonic reconstructions,geology,geodynamics,continental growth,mountain belts,subducted ocean basins,paleomagnetism
Projet ERC : DEEP TIME (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1346219.64 €

DEEP TIME will unearth a record of geological time that is buried thousands of kilometres deep. The seafloor that covers two-thirds of the earth's surface is a tiny fraction of all seafloor created during its history – the rest has sunk back into the viscous mantle. Slabs of subducted seafloor carry a record of surface history: how continents and oceans were configured over time and where their tectonic plate boundaries lay. DEEP TIME will follow former surface oceans as far back in time as the convecting mantle system will permit, by imaging subducted slabs down to the core with cutting-edge seismological techniques. Current tectonic plate reconstructions incorporate little if any of this deep structural information, which probably reaches back 300+ million years; they are based on present-day seafloor, which constrains only the past 100-150 million years. DEEP TIME will match deep slab structure to the geological surface record of subduction – volcanic arcs and other crustal slivers that stayed afloat, survived collisions, and form the world’s largest mountain belts. Integrating these two direct records of subduction, the project will * Add paleo-trenches to existing plate reconstructions and extend them 2-3 times longer into the past. * Produce a 3-D atlas of the mantle that matches subducted seafloor with paleo-oceans inferred by land geology. * Rigorously test the hypothesis of vertical slab sinking, which may yield an absolute mantle reference frame. Tomographic models and geological land records will be synthesized into quantitative and testable paleogeographic reconstructions that complement and extend existing ones, especially in paleo-oceanic areas. This is likely to transform our understanding of the earth’s physical surface environment and biosphere during Mesozoic times, as well as the formation of natural resources. It also will put observational constraints on elusive mantle rheologies. Nearly every subdiscipline of the earth sciences could benefit.

Mots-clés : mantle structure,seismic tomography,plate tectonic reconstructions,geology,geodynamics,continental growth,mountain belts,subducted ocean basins,paleomagnetism
Projet ERC : DEEPVOLC (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of Leeds — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1941270.0 €

DEEPVOLC will radically advance the way future activity is forecast at volcanoes by applying advances in artificial intelligence to transformative new geodetic datasets. 200 million people live within 30 km of a volcano. Accurate forecasting of volcanic eruptions is problematic because 1) it relies on human interpretation at individual volcanoes, 2) a volcano can behave in unexpected ways not previously seen at that location, and 3) most volcanoes are not instrumented. DEEPVOLC will address this by i) applying artificial intelligence, ii) using data for all volcanoes worldwide, and iii) exploiting advances in satellite monitoring. A key indicator of potential volcanic activity is deformation of a volcano's surface due to magma migrating beneath. Surface movements as small as a few millimetres can now be measured from space, using satellite-borne radar. A recently-launched European satellite mission, Sentinel-1, has transformed our ability to measure surface deformation at all of the world's volcanoes, acquiring data at least twice every twelve days. However, forecasting how deforming volcanoes will behave in the future remains challenging. In this project I will apply recently developed deep learning approaches to the satellite data. This is an entirely new approach to forecasting volcanic activity, which currently relies on the individual expertise available at each observatory, and which is only now made possible due to the launch of Sentinel-1 and advances in deep learning algorithms. DEEPVOLC will combine knowledge from all volcanoes that have been active in the era of satellite deformation observations, and will continue to improve as it ingests data from new activity. The main deliverable will be a system for volcano observatories that uses knowledge of how volcanoes behave globally to automatically identify deformation at volcanoes locally, and forecast how the deformation will evolve, indicating the probability of eruption.

Mots-clés : insar,sentinel 1,volcano deformation,deep learning,neural networks
Projet ERC : DISCRETION (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : University of Bergen — Pays : Norvège — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1997918.0 €

DISCRETION aims to unlock the black box of discretionary decision-making in child protection cases by a comparative-empirical study of how discretionary decisions are made and justified in the best interests of the child. There are huge research gaps in this important area of the welfare state, with a great deal of uncertainty concerning how, when and why discretionary decisions about the child´s best interests are different between decision-makers within and between child protection systems. The main objectives for this project are to reveal the mechanisms for exercising discretion, and improve the understanding of the principle of the child´s best interests. These objectives will be reached by systematically examining the role of institutional, organisational and individual factors including regulations of best interest principles; professions involved; type of courts; type of child protection system; demographic factors and individual values; and the populations’ view on children and paternalism. DISCRETION employs an innovative methodological approach, with multilevel and cross-country studies. DISCRETION will, by conducting the largest cross-national study on decision-making in child protection to date, lift our understanding of international differences in child protection to a new level. By conducting randomized survey experiments with both decision-makers in the system and the general population, DISCRETION generates unique data on the causal mechanisms explaining differences in discretionary decisions. The outcomes of DISCRETION are important because societies are at a crossroad when it comes to how children are treated and how their rights are respected, which creates tensions in the traditional relationship between the family and the state. DISCRETION will move beyond the field of child protection and provide important insights into the exercise of discretion in all areas where the public interest as well as national interest must be interpreted.

Mots-clés : children s rights,child protection systems,discretionary reasoning,paternalism,social legal decision making
Projet ERC : altEJrepair (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : Partner
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 310078.75 €

DNA repair pathways evolved as an intricate network that senses DNA damage and resolves it in order to minimise genetic lesions and thus preventing tumour formation. Gaining in recognition the last few years, the alternative end-joining (alt-EJ) DNA repair pathway was recently shown to be up-regulated and required for cancer cell viability in the absence of homologous recombination-mediated repair (HR). Despite this integral role, the alt-EJ repair pathway remains poorly characterised in humans. As such, its molecular composition, regulation and crosstalk with HR and other repair pathways remain elusive. Additionally, the contribution of the alt-EJ pathway to tumour progression as well as the identification of a mutational signature associated with the use of alt-EJ has not yet been investigated. Moreover, the clinical relevance of developing small-molecule inhibitors targeting players in the alt-EJ pathway, such as the polymerase Pol Theta (Polθ), is of importance as current anticancer drug treatments have shown limited effectiveness in achieving cancer remission in patients with HR-deficient (HRD) tumours. Here, we propose a novel, multidisciplinary approach that aims to characterise the players and mechanisms of action involved in the utilisation of alt-EJ in cancer. This understanding will better elucidate the changing interplay between different DNA repair pathways, thus shedding light on whether and how the use of alt-EJ contributes to the pathogenic history and survival of HRD tumours, eventually paving the way for the development of novel anticancer therapeutics. For all the abovementioned reasons, we are convinced this project will have important implications in: 1) elucidating critical interconnections between DNA repair pathways, 2) improving the basic understanding of the composition, regulation and function of the alt-EJ pathway, and 3) facilitating the development of new synthetic lethality-based chemotherapeutics for the treatment of HRD tumours.

Mots-clés : dna repair,alternative end joining,homologous recombination,synthetic lethality
Projet ERC : REPLICONSTRAINTS (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
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 : 1498898.75 €

DNA replication is essential for the perpetuation of life and, yet, it is also a major source of genomic instability that can lead to cancer and other human diseases. Despite the vast efforts invested in establishing the origins of genomic instability, the mechanisms that coordinate faithful genome duplication while ensuring its integrity remain unknown. This dilemma is molecularly best exemplified by single stranded DNA (ssDNA), which inevitably results from unwinding the double helix due to replication fork progression, but is at the same time a vulnerable intermediate that can lead to severe genomic lesions. Thus, maintaining an appropriate balance of ssDNA is a paramount challenge for replicating cells. My own work has significantly contributed to this concept by showing that eukaryotic cells have limited resources to guard its ssDNA, and that exhaustion of these resources (due to increased overall levels of ssDNA) causes a lethal fragmentation of the genome termed ‘replication catastrophe’ (RC). To prevent this terminal scenario, ssDNA levels and DNA replication activity must be constrained by yet uncharacterized mechanisms. In eukaryotes, where DNA is simultaneously replicated at multiple sites throughout the genome, this represents a particularly challenging task. Understanding how this is molecularly accomplished could transform our view of the very principles of DNA replication regulation, and also reveal potential therapeutic avenues to exploit RC in the treatment for cancer. With the present proposal I will address this challenge by investigating how ssDNA maintenance is enrooted in the regulatory principles of DNA replication. I will dissect the mechanisms that, globally and locally, constrain replication activity to prevent genomic instability. By using novel and innovative analytical tools, I aim to provide an unmatched picture of the DNA replication apparatus and to identify novel anticancer strategies based on provoking RC selectively in tumor cells.

Mots-clés : dna replication,genomic instability