Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : 3D-REPAIR (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Sussex — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 776220.45 €

Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown. Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps. This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer

Mots-clés : nuclear organization,dna repair,chromatin,chromosomes
Projet ERC : ADMIRE (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Universität Hamburg — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : UHH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499750.0 €

Fault-tolerant topological quantum computation has become one of the most exciting research directions in modern condensed matter physics. As a key operation the braiding of non-Abelian anyons has been proposed theoretically. Such exotic quasiparticles can be realized as zero-energy Majorana bound states at the ends of one-dimensional magnetic nanowires in proximity to s-wave superconductors in the presence of high spin-orbit coupling. In contrast to previous attempts to realize such systems experimentally, based on the growth of semiconducting nanowires or the self-assembly of ferromagnetic nanowires on s-wave superconductors, we propose to design Majorana bound states in artificially constructed single-atom chains with non-collinear spin-textures on elemental superconducting substrates using scanning tunnelling microscope (STM)-based atom manipulation techniques. We would like to study at the atomic level the formation of Shiba bands as a result of hybridization of individual Shiba impurity states as well as the emergence of zero-energy Majorana bound states as a function of chain structure, length, and composition. Moreover, we will construct model-type platforms, such as T-junctions, rings, and more complex network structures with atomic-scale precision as a basis for demonstrating the manipulation and braiding of Majorana bound states. We will make use of sophisticated experimental techniques, such as spin-resolved scanning tunnelling spectroscopy (STS) at micro-eV energy resolution, scanning Josephson tunnelling spectroscopy, and multi-probe STS under well-defined ultra-high vacuum conditions, in order to directly probe the nature of the magnetic state of the atomic wires, the spin-polarization of the emergent Majorana states, as well as the spatial nature of the superconducting order parameter in real space. Finally, we will try to directly probe the quantum exchange statistics of non-Abelian anyons in these atomically precise fabricated model-type systems.

Mots-clés : emergent exotic states of condensed matter,majorana states,bottom up designed nanostructures
Projet ERC : FeedHypNet (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 401015.4 €

Feeding behaviors represent a complex set of crucial for survival abilities required to meet upcoming nutritional demands. Eating disorders, such as anorexia nervosa, are widespread, difficult to treat and extremely dangerous, displaying the highest mortality rate of all psychiatric disorders and a very high relapse rate. Mechanisms of onset, progression and relapse of eating disorders are unknown. Feeding behaviors are regulated by hypothalamus, an evolutionary conservative brain region. While a role of neurochemically defined hypothalamic neurons in feeding has been recently studied, little is known about an adaptive regulation of hypothalamus by extrahypothalamic inputs. Further, it is not known how dynamic signaling in hypothalamus upon changing metabolic and environmental demands is organized to generate consistent adaptive behavior. The overarching goal of my proposal is to provide insight into neural mechanisms of healthy and pathological feeding behaviors. Combining optogenetics, electrophysiological recordings in transgenic behaving mice, Ca2+ imaging and fiber photometry, I will pursue 4 aims: (i) investigate role of neural circuitries that translate cognitive-related information to the lateral hypothalamus during adaptive feeding behaviors; (ii) characterize causal significance of top-down inputs from anxiety- and mood-related brain regions onto lateral hypothalamus in feeding, and study how changes in metabolic demands affect this signaling; (iii) study mechanisms and functions of fast, network oscillations-related and behavior-dependent signaling in hypothalamus; (iv) investigate how signaling in hypothalamus changes during development of anorexia nervosa symptoms and study consequences of optogenetically restored physiological signaling. This innovative and interdisciplinary approach will enable identification of neuronal circuits mediating feeding behavior in health and pathology, and thus gain insights into neuronal mechanisms of eating disorders.

Mots-clés : neuronal circuits,hypothalamus,prefrontal cortex,inhibition,neuropeptides,orexin,gaba,network oscillations,feeding,behaving mice,optogenetics,in vivo electrophysiology,eating disorders
Projet ERC : DORMANTOOCYTE (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Centre for Genomic Regulation — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CRG;CRG-CERCA
Type d'entité : Recherche
Financement ERC de l'entité : 1381286.0 €

Female germ cells, oocytes, are highly specialised cells. They ensure the continuity of species by providing the female genome and mitochondria along with most of the nutrients and housekeeping machinery the early embryo needs after fertilisation. Oocytes are remarkable in their ability to survive for long periods of time, up to 50 years in humans, and retain the ability to give rise to a young organism while other cells age and die. Surprisingly little is known about oocyte dormancy. A key feature of dormant oocytes of virtually all vertebrates is the presence of a Balbiani body, which is a non-membrane bound compartment that contains most of the organelles in dormant oocytes and disappears as the oocyte matures. The goal of this proposal is to combine genetic and biochemical perturbations with imaging and the state of the art proteomics techniques to reveal the mechanisms dormant oocytes employ to remain viable. My previous research has shown that the Balbiani body forms an amyloid-like cage around organelles that could be protective. This has led me to identify the large number of unanswered questions about the cell biology of a dormant oocyte. In this proposal, we will study three of these questions: 1) What is the metabolic nature of organelles in dormant oocytes? 2) How does the Balbiani body disassemble and release the complement of organelles when oocytes start to mature? 3) What is the structure and function of the Balbiani body in mammals? We will use oocytes from two vertebrate species, frogs and mice, which are complementary for their ease of handling and relationship to human physiology. By studying the Balbiani body, this proposal will provide fundamental insights into organisation and function of organelles in oocytes and the regulation of physiological amyloid-like structures. More generally, the proposed experiments open up new avenues into the mechanisms that protect organelles from ageing and how oocytes stay dormant for many decades.

Mots-clés : balbiani body,spatial organization of the dormant oocyte,and the function of its organelles
Projet ERC : Sperm-Egg Phusion (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 2499375.0 €

Fertilization is essential for a species to survive. Mammalian sexual reproduction requires the fusion between the haploid gametes sperm and egg to create a new diploid organism. Although fertilization has been studied for decades, and despite the remarkable recent discoveries of Izumo (on sperm) and Juno (on oocytes) as a critical ligand:receptor pair, due to the structure of Izumo and Juno, it is clear that other players on both the sperm and the oocytes must be involved. While the focus of our laboratory over the years has been in understanding apoptotic cell clearance by phagocytes, we accidentally noted that viable, motile, and fertilization-competent sperm exposes phosphatidylserine (PtdSer). PtdSer is a phospholipid normally exposed during apoptosis and functions as an ‘eat-me’ signal for phagocytosis. Further, masking this PtdSer on sperm inhibits fertilization in vitro. Based on additional exciting preliminary data, in this ERC proposal, we will test the hypothesis that PtdSer on viable sperm and the complementary PtdSer receptors on oocytes are key players in mammalian fertilization. We will test this at a molecular, biochemical, cellular, functional, and genetic level. From the sperm perspective — we will ask how does PtdSer changes during sperm maturation, and what molecular mechanisms regulate the exposure of PtdSer on viable sperm. From the oocyte perspective — we will test the genetic relevance of different PtdSer receptors in fertilization. From the PtdSer perspective — we will test PtdSer induces novel signals within oocytes. By combining the tools and knowledge from field of phagocytosis with tools from spermatogenesis/fertilization, this proposal integrates fields that normally do not intersect. In summary, we believe that these studies are innovative, timely, and will identify new players involved in mammalian fertilization. We expect the results of these studies to have high relevance to both male and female reproductive health and fertility.

Mots-clés : phosphatidylserine,phagocytosis,efferocytosis,phagocytic receptors,ptdser receptors,apoptosis,bai1,cd36,elmo,cytoskeletal reorganization,myoblast fusion,bai3,cell fusion
Projet ERC : CLUSTER (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : École normale supérieure PSL — Pays : France — Rôle : Partner
Acronyme de l'entité : ENS PSL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 24118.76 €

Few geophysical phenomena are as spectacular as tropical cyclones, with their eye surrounded by sharp cloudy eyewalls. There are other types of spatially organised convection (convection refers to overturning of air within which clouds are embedded), in fact organised convection is ubiquitous in the tropics. But it is still poorly understood and poorly represented in convective parameterisations of global climate models, despite its strong societal and climatic impact. It is associated with extreme weather, and with dramatic changes of the large scales, including drying of the atmosphere and increased outgoing longwave radiation to space. The latter can have dramatic consequences on tropical energetics, and hence on global climate. Thus, convective organisation could be a key missing ingredient in current estimates of climate sensitivity from climate models. CLUSTER will lead to improved fundamental understanding of convective organisation to help guide and improve convective parameterisations. It is closely related to the World Climate Research Programme (WCRP) grand challenge: Clouds, circulation and climate sensitivity. Grand challenges identify areas of emphasis in the coming decade, targeting specific barriers preventing progress in critical areas of climate science. Until recently, progress on this topic was hindered by high numerical cost and lack of fundamental understanding. Advances in computer power combined with new discoveries based on idealised frameworks, theory and observational findings, make this the ideal time to determine the fundamental processes governing convective organisation in nature. Using a synergy of theory, high-resolution cloud-resolving simulations, and in-situ and satellite observations, CLUSTER will specifically target two feedbacks recently identified as being essential to convective aggregation, and assess their impact on tropical cyclones, large-scale properties including precipitation extremes, and energetics of the tropics.

Mots-clés : deep convection in the tropics,self aggregation of deep convection
Projet ERC : HistoGenes (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Landesamt für Denkmalpflege und Archäologie Sachsen-Anhalt — Pays : Allemagne — Rôle : Partner
Type d'entité : Organismes publics (hors enseignement & recherche)
Financement ERC de l'entité : 0.0 €

Few parts of Europe witnessed so many population shifts in a few centuries as the Carpathian Basin in 400-900 CE. In this macro-region along the middle Danube, Pannonians, Romans, Goths, Gepids, Longobards, Avars, Bulgars, Slavs, Franks and many others came and went. This is an intriguing test case for the relationship between ethnic identities constructed in texts, cultural habitus attested in the archaeological record, and genetic profiles that can now be analysed through ancient DNA. What was the impact of migrations and mobility on the population of the Carpathian Basin? Was the late antique population replaced, did it mix with the newcomers, or did its descendants only adopt new cultural styles? To what degree did biological distinctions correspond to the cultural boundaries and/or ethnonyms in the texts? If pursued with methodological caution, this case study will have implications beyond the field. HistoGenes will analyse c. 6,000 samples from graves with cutting edge scientific methods, and contextualize the interpretation of these data in their archaeological and historical setting. The rapid progress of aDNA analysis and of bio-informatics now make such an enterprise viable. However, the methods of historical interpretation have not kept pace. HistoGenes will, for the first time, unite historians, archaeologists, geneticist, anthropologists, and specialists in bio-informatics, isotope analysis and other scientific methods. Many team members have already collaborated successfully in a pilot project, which has demonstrated the feasibility of the approach and of the integrated workflow at the core of the project. A wide range of particular historical questions will be addressed from an interdisciplinary perspective, and fundamental theoretical and methodological issues can be explored. HistoGenes will not only advance our knowledge about a key period in European history, but also establish new standards for the historical interpretation of genetic data.

Mots-clés : early middle ages,late antiquity,migration,ethnicity,transformation of the roman world,historical method,interdisciplinary method,steppe empires
Projet ERC : HistoGenes (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Hungarian Natural History Museum — Pays : Hongrie — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 0.0 €

Few parts of Europe witnessed so many population shifts in a few centuries as the Carpathian Basin in 400-900 CE. In this macro-region along the middle Danube, Pannonians, Romans, Goths, Gepids, Longobards, Avars, Bulgars, Slavs, Franks and many others came and went. This is an intriguing test case for the relationship between ethnic identities constructed in texts, cultural habitus attested in the archaeological record, and genetic profiles that can now be analysed through ancient DNA. What was the impact of migrations and mobility on the population of the Carpathian Basin? Was the late antique population replaced, did it mix with the newcomers, or did its descendants only adopt new cultural styles? To what degree did biological distinctions correspond to the cultural boundaries and/or ethnonyms in the texts? If pursued with methodological caution, this case study will have implications beyond the field. HistoGenes will analyse c. 6,000 samples from graves with cutting edge scientific methods, and contextualize the interpretation of these data in their archaeological and historical setting. The rapid progress of aDNA analysis and of bio-informatics now make such an enterprise viable. However, the methods of historical interpretation have not kept pace. HistoGenes will, for the first time, unite historians, archaeologists, geneticist, anthropologists, and specialists in bio-informatics, isotope analysis and other scientific methods. Many team members have already collaborated successfully in a pilot project, which has demonstrated the feasibility of the approach and of the integrated workflow at the core of the project. A wide range of particular historical questions will be addressed from an interdisciplinary perspective, and fundamental theoretical and methodological issues can be explored. HistoGenes will not only advance our knowledge about a key period in European history, but also establish new standards for the historical interpretation of genetic data.

Mots-clés : early middle ages,late antiquity,migration,ethnicity,transformation of the roman world,historical method,interdisciplinary method,steppe empires
Projet ERC : HistoGenes (Horizon 2020, appel 2019, Synergy grants)
Entité participante : Research Foundation for the State University of New York — Pays : Etats-Unis — Rôle : Partner
Acronyme de l'entité : RF SUNY
Type d'entité : Autres
Financement ERC de l'entité : 1127863.75 €

Few parts of Europe witnessed so many population shifts in a few centuries as the Carpathian Basin in 400-900 CE. In this macro-region along the middle Danube, Pannonians, Romans, Goths, Gepids, Longobards, Avars, Bulgars, Slavs, Franks and many others came and went. This is an intriguing test case for the relationship between ethnic identities constructed in texts, cultural habitus attested in the archaeological record, and genetic profiles that can now be analysed through ancient DNA. What was the impact of migrations and mobility on the population of the Carpathian Basin? Was the late antique population replaced, did it mix with the newcomers, or did its descendants only adopt new cultural styles? To what degree did biological distinctions correspond to the cultural boundaries and/or ethnonyms in the texts? If pursued with methodological caution, this case study will have implications beyond the field. HistoGenes will analyse c. 6,000 samples from graves with cutting edge scientific methods, and contextualize the interpretation of these data in their archaeological and historical setting. The rapid progress of aDNA analysis and of bio-informatics now make such an enterprise viable. However, the methods of historical interpretation have not kept pace. HistoGenes will, for the first time, unite historians, archaeologists, geneticist, anthropologists, and specialists in bio-informatics, isotope analysis and other scientific methods. Many team members have already collaborated successfully in a pilot project, which has demonstrated the feasibility of the approach and of the integrated workflow at the core of the project. A wide range of particular historical questions will be addressed from an interdisciplinary perspective, and fundamental theoretical and methodological issues can be explored. HistoGenes will not only advance our knowledge about a key period in European history, but also establish new standards for the historical interpretation of genetic data.

Mots-clés : early middle ages,late antiquity,migration,ethnicity,transformation of the roman world,historical method,interdisciplinary method,steppe empires
Projet ERC : AsthmaPhenotypes (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
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 : 255880.0 €

Fifteen years ago it was widely believed that asthma was an allergic/atopic disease caused by allergen exposure in infancy; this produced atopic sensitization and continued exposure resulted in eosinophilic airways inflammation, bronchial hyper-responsiveness and reversible airflow obstruction. It is now clear that this model is at best incomplete. Less than one-half of asthma cases involve allergic (atopic) mechanisms, and most asthma in low-and-middle income countries is non-atopic. Westernization may be contributing to the global increases in asthma prevalence, but this process appears to involve changes in asthma susceptibility rather than increased exposure to “established” asthma risk factors. Understanding why these changes are occurring is essential in order to halt the growing global asthma epidemic.This will require a combination of epidemiological, clinical and basic science studies in a variety of environments. A key task is to reclassify asthma phenotypes. These are important to: (i) better understand the aetiological mechanisms of asthma; (ii) identify new causes; and (iii) identify new therapeutic measures. There are major opportunities to address these issues using new techniques for sample collection from the airways (sputum induction, nasal lavage), new methods of analysis (microbiome, epigenetics), and new bioinformatics methods for integrating data from multiple sources and levels. There is an unprecedented potential to go beyond the old atopic/non-atopic categorization of phenotypes. I will therefore conduct analyses to re-examine and reclassify asthma phenotypes. The key features are the inclusion of: (i) both high and low prevalence centres from both high income countries and low-and-middle income countries; (ii) much more detailed biomarker information than has been used for previous studies of asthma phenotypes; and (iii) new bioinformatics methods for integrating data from multiple sources and levels.

Mots-clés : asthma,epidemiology,phenotypes