Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : Epi4MS (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Karolinska Institutet — Pays : Suède — Rôle : PI
Acronyme de l'entité : KI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1998798.0 €

Multiple Sclerosis (MS) is a leading cause of unpredictable and incurable progressive disability in young adults. Although the exact cause remains unknown, this immune-mediated disease is likely triggered by environmental factors in genetically predisposed individuals. I propose that epigenetic mechanisms, which regulate gene expression without affecting the genetic code, mediate the processes that cause MS and that aberrant epigenetic states can be corrected, spearheading the development of alternative therapies. We will exploit the stable and reversible nature of epigenetic marks, in particular DNA methylation, to gain insights into the novel modifiable disease mechanisms by studying the target organ in a way that has not been possible before. This highly ambitious project comprises three synergistic facets formulated in specific aims to: (i) identify epigenetic states that characterize the pathogenesis of MS, (ii) prioritize functional epigenetic states using high-throughput epigenome-screens, and (iii) develop novel approaches for precision medicine based on correcting causal epigenetic states. Our unique MS biobank combined with cutting-edge methodologies to capture pathogenic cells and measure their functional states provides a rational starting point to identify MS targets. I will complement this approach with studies of the functional impact of MS targets using innovative in vitro screens, with the added value of unbiased discovery of robust regulators of specific MS pathways. Finally, my laboratory has extensive experience with animal models of MS and I will utilize these powerful systems to dissect molecular mechanisms of MS targets and test the therapeutic potential of targeted epigenome editing in vivo. Our findings will set the stage for a paradigm-shift in studying and treating chronic inflammatory diseases based on preventing and modulating aggressive immune responses by inducing self-sustained reversal of aberrant epigenetic states.

Mots-clés : multiple sclerosis,epigenetics,dna methylation,epigenome editing,autoimmunity,adaptive immunity,neuroinflammation,animal models,functional genetics
Projet ERC : H I C I (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 86299.01 €

Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS), in which chronic inflammation and failure of regenerative mechanisms lead to progressive tissue destruction and accumulation of neurological deficits. Glial cells such as astrocytes induce regenerative processes in acute inflammation, but fail to inhibit tissue destruction for yet unknown reasons in chronic disease. In preliminary studies, we identified heparin-binding EGF-like growth factor (HB-EGF) in astrocytes as novel tissue protective factor. Indeed, knock-down of HB-EGF in astrocytes led to exacerbated disease and failure to recover in an animal model of MS. Promoter studies revealed induction of HB-EGF by the ligand-induced transcription factor aryl hydrocarbon receptor (AHR) in acute inflammation. However, astrocytic HB-EGF decreased in chronic stages concomitantly with progressive disease worsening. Analyses of AHR binding sites in the HB-EGF promoter revealed epigenetic modifications mediated by DNA-Methyltransferase 1 (DNMT1) in chronic inflammation, which inhibited promoter activation by AHR. Knocking down DNMT1 prevented epigenetic changes and increased HB-EGF production in chronic stages. Thus, we have discovered astrocytic HB-EGF as a novel regenerative factor and its regulation by AHR and DNMT1, which could be targeted therapeutically to enhance tissue regeneration in chronic stages. In this project, we will define the role of HB-EGF in acute and chronic autoimmune CNS inflammation (Aim 1), its regulation by AHR and DNMT1 (Aim 2), and the therapeutic value of nasal HB-EGF application or DNMT1 blockade (Aim 3). In a translational approach, we will validate AHR ligands, HB-EGF and HB-EGF promoter methylation status in serum and cerebrospinal fluid of MS patients as novel biomarkers for MS (Aim 4). These high risk/high gain studies explore novel concepts for monitoring and therapy of yet untreatable stages of MS and other degenerative diseases of the CNS.

Mots-clés : cns regeneration,tissue protection,hb egf,astrocyte,epigenetic modification
Projet ERC : H I C I (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Universitätsklinikum Erlangen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1413406.99 €

Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS), in which chronic inflammation and failure of regenerative mechanisms lead to progressive tissue destruction and accumulation of neurological deficits. Glial cells such as astrocytes induce regenerative processes in acute inflammation, but fail to inhibit tissue destruction for yet unknown reasons in chronic disease. In preliminary studies, we identified heparin-binding EGF-like growth factor (HB-EGF) in astrocytes as novel tissue protective factor. Indeed, knock-down of HB-EGF in astrocytes led to exacerbated disease and failure to recover in an animal model of MS. Promoter studies revealed induction of HB-EGF by the ligand-induced transcription factor aryl hydrocarbon receptor (AHR) in acute inflammation. However, astrocytic HB-EGF decreased in chronic stages concomitantly with progressive disease worsening. Analyses of AHR binding sites in the HB-EGF promoter revealed epigenetic modifications mediated by DNA-Methyltransferase 1 (DNMT1) in chronic inflammation, which inhibited promoter activation by AHR. Knocking down DNMT1 prevented epigenetic changes and increased HB-EGF production in chronic stages. Thus, we have discovered astrocytic HB-EGF as a novel regenerative factor and its regulation by AHR and DNMT1, which could be targeted therapeutically to enhance tissue regeneration in chronic stages. In this project, we will define the role of HB-EGF in acute and chronic autoimmune CNS inflammation (Aim 1), its regulation by AHR and DNMT1 (Aim 2), and the therapeutic value of nasal HB-EGF application or DNMT1 blockade (Aim 3). In a translational approach, we will validate AHR ligands, HB-EGF and HB-EGF promoter methylation status in serum and cerebrospinal fluid of MS patients as novel biomarkers for MS (Aim 4). These high risk/high gain studies explore novel concepts for monitoring and therapy of yet untreatable stages of MS and other degenerative diseases of the CNS.

Mots-clés : cns regeneration,tissue protection,hb egf,astrocyte,epigenetic modification
Projet ERC : Mushroomics (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Utrecht University — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Mushrooms are the sexual reproductive structures of basidiomycetes. Much remains to be learned about the molecular regulation of mushroom development. Only a few genes have been implicated in this process, but their exact function remains unknown. Schizophyllum commune is a model system for mushroom-forming fungi. It was recently shown that this species shows the highest intraspecies DNA variability in eukaryotes with 150 SNPs per 1000 base pairs, yet they can still reproduce sexually. This hypervariabity is also illustrated by variability in the response to environmental factors that initiate mushroom development and by the differences in morphology within this species. I propose a functional genomics approach to elucidate the molecular genetics of mushroom development. We have a collection of 100 S. commune strains sampled world-wide. I propose to leverage the extraordinary diversity among these strains. I will identify genes that explain differences in mushroom morphology and in responses to environmental stimuli such as light and CO2. The genes/alleles responsible for these phenotypes will by mapped by genome sequencing followed by bulk segregant analysis. Transcription factors (TFs) are expected to play an important role in regulation of mushroom development. Therefore I propose to systematically study TF function by generating a knock-down collection of all predicted 313 TFs. The phenotypes of the resulting strains will be analyzed and target genes of TFs will be identified by RNA-Seq and ChIP-Seq. The genes identified by these strategies will subsequently be analyzed to determine their function. My initial results demonstrate the feasibility of this approach. The availability of the strain collection, the available molecular toolbox, and my strong expertise both in genomics and molecular biology of mushroom development will enable me to take a huge step forward in our understanding of mushroom development.

Mots-clés : development,developmental genetics and pattern formation in fungi,eukaryotic microbiology
Projet ERC : CAASD (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Shanghai Normal University — Pays : Chine — Rôle : Partner
Acronyme de l'entité : SHNU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 57060.0 €

Music and language share similar properties and are processed in overlapping brain regions. As a common information-bearing element in music and language, pitch plays an essential role in encoding musical melodies, signifying linguistic functions, and conveying emotions through music and speech. However, two distinct neurodevelopmental disorders, congenital amusia (CA) and autism spectrum disorders (ASD), affecting millions of people in Europe and worldwide, may selectively impair individuals’ ability to process musical, linguistic, and emotional pitch. To date, it remains unclear why individuals with CA and ASD exhibit significant differences in music, speech, and emotion processing. Under our Delicate Form-Function Balance Hypothesis, we will conduct a series of behavioural and neurophysiological experiments to test the central hypothesis that normal musical, linguistic, and emotional functioning requires a delicate balance in the encoding and decoding of form and function in musical, speech, and emotional communication, with musical communication centred on form and linguistic and emotional communication focused on function. Most critically, we hypothesize that the differences in music, speech, and emotional processing in CA and ASD are rooted not only in pitch and cognitive abilities, but also in the balance between form and function for each domain. Addressing three specific aims regarding the impacts of cognitive processing styles, pitch processing skills, and language background (tone vs. non-tonal) on the behavioural and neurophysiological characteristics of music, language, and emotion processing in CA and ASD, this research will not only help reveal the underlying mechanisms of the two defining aspects of human cognition, music and language, but also form a laboratory for testing key hypotheses about the bio-behavioural manifestations of human neurodevelopmental disorders in music and language processing.

Mots-clés : music,language,emotion,pitch,congenital amusia,autism spectrum disorders,form,function,cognitive processing
Projet ERC : CAASD (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Reading — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1431754.0 €

Music and language share similar properties and are processed in overlapping brain regions. As a common information-bearing element in music and language, pitch plays an essential role in encoding musical melodies, signifying linguistic functions, and conveying emotions through music and speech. However, two distinct neurodevelopmental disorders, congenital amusia (CA) and autism spectrum disorders (ASD), affecting millions of people in Europe and worldwide, may selectively impair individuals’ ability to process musical, linguistic, and emotional pitch. To date, it remains unclear why individuals with CA and ASD exhibit significant differences in music, speech, and emotion processing. Under our Delicate Form-Function Balance Hypothesis, we will conduct a series of behavioural and neurophysiological experiments to test the central hypothesis that normal musical, linguistic, and emotional functioning requires a delicate balance in the encoding and decoding of form and function in musical, speech, and emotional communication, with musical communication centred on form and linguistic and emotional communication focused on function. Most critically, we hypothesize that the differences in music, speech, and emotional processing in CA and ASD are rooted not only in pitch and cognitive abilities, but also in the balance between form and function for each domain. Addressing three specific aims regarding the impacts of cognitive processing styles, pitch processing skills, and language background (tone vs. non-tonal) on the behavioural and neurophysiological characteristics of music, language, and emotion processing in CA and ASD, this research will not only help reveal the underlying mechanisms of the two defining aspects of human cognition, music and language, but also form a laboratory for testing key hypotheses about the bio-behavioural manifestations of human neurodevelopmental disorders in music and language processing.

Mots-clés : music,language,emotion,pitch,congenital amusia,autism spectrum disorders,form,function,cognitive processing
Projet ERC : ORIGINS (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
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 : 1996027.0 €

Mutualism between plants and microorganisms has been essential for the evolution of terrestrial ecosystems for millions of years. It has been proposed that even the colonization of lands by plants was facilitated by a mutualistic symbiosis formed with arbuscular mycorrhizal fungi. This symbiosis, by far the most widespread in land plants, results in the accommodation of the symbiotic fungus inside the plant cells. Following this initial symbiosis, multiple other intracellular symbioses have evolved in plants as diverse as orchids, Ericaceae such as cranberry, legumes or the Jungermanniales, a group of bryophytes. These symbioses provide numerous benefits, improving plant nutrient acquisition and fitness. Despite their absolute importance in terrestrial ecosystems, the molecular mechanisms underlying the origin and subsequent evolution of intracellular symbioses in plants remain poorly understood. In a first objective, we will use CRISPR/Cas9 in the bryophyte Marchantia paleacea to test the conservation across land plants of symbiotic mechanisms known in angiosperms. Then, we will decipher how these mechanisms evolved by comparing land plants with their closest algal relatives. In a second objective, we will conduct transcriptomics coupled with genetic manipulations of most known intracellular symbioses in plants. This will allow determining how the ability to host intracellularly microbial symbionts recruited in the environment evolved repeatedly in land plants and how functional specificity evolved in these different symbioses. Lastly, we will investigate why the evolution of intracellular symbioses is constrained to a unique genetic pathway. Through this project, combining phylogenomics, biochemistry, transcriptomics and genetic validations in six plant lineages covering more than 500 million years of evolution, we will provide a comprehensive understanding of the molecular mechanisms underlying the evolution of intracellular mutualistic symbioses in plants.

Mots-clés : plant symbioses,evo devo,marchantia,arbuscular mycorrhizal symbiosis,gene regulatory networks,zygnematophyceae
Projet ERC : MwHresEP (Horizon 2020, appel 2016, Proof of concept grants)
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

MwHresEP: Multi-well High-resolution Electrophysiology Platform The aim of this proof-of-concept project is to make initial steps in translating the high-density microelectrode array (HD-MEA) chip technology, which has been developed in the ERC project “NeuroCMOS” (AdG 267351, Subproject 1) into a commercial product. The project will be performed in collaboration with the spin-off company MaxWell Biosystems AG (http://www.mxwbio.com/) that has been founded after the NeuroCMOS project end by collaborators of the PI laboratory and a lab at Riken (Japan) with the purpose to commercialize the developed CMOS-based chip technology and software for neuroscientific research and industrial use in drug discovery and development. The initial steps undertaken in this PoC include (i) the development of a multi-well-plate prototype, suitable for drug discovery applications, that can host CMOS microelectrode arrays in each well. Moreover, we will (ii) develop the needed soft- and hardware to prove the feasibility of integrating the chip system prototype into cell-culture automation platforms, and we will work to (iii) obtain initial data from commercially available human induced-pluripotent-stem-cell (iPSC) -derived neurons.

Mots-clés : electrophysiology,microelectrode arrays,extracellular recording,well plate multi well plate,drug screening,human induced pluripotent stem cells
Projet ERC : UTHC (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Université Catholique de Louvain — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UCL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1311263.0 €

My aim is to determine the role of elite knowledge and upper-tail human capital (UTHC) in triggering the rise of the West. I propose to build a database of a large sample of academic scholars in Europe over the period 1000CE-1800CE. Sources will be primary (published cartularia and matricula), secondary (books on the history of universities & academies), and tertiary (biographical dictionaries). To measure the quality of scholars, these data will be matched with the existing catalogues of publications. Second, we will build a geographical grid of the density, composition, and quality of the UTHC across time, and correlate the UTHC at the cell level with the adoption of new techniques and better institutions, and the development of literacy, numeracy, and urbanization. The individual character of the data will allow basing causal identification on exogenous variations in the European network of both individuals and universities. The migration pattern of scholars will be used to identify sorting and agglomeration forces, witnessing to the functioning of an academic market in the medieval and early modern periods. Families of scholars will be identified to assess the importance of nepotism vs human capital transmission. Third, we will develop a new theory of the complementarity between sciences and techniques, to deter-mine the incentives under which codified knowledge and practical skills interact, and ideas spread. A second new theoretical model will be devoted to revealing the dynamic interactions between conservative and modern forces within universities and learned societies; the key trade-off here is between vested interests and new paradigms, letting scholarly elites develop a culture of growth. With the data gathered, we will be able to measure the importance of these theoretical mechanisms and how the UTHC and society interact. Overall, I intend to rethink economic growth by unraveling the rich interactions between scholars & literati and its emergence.

Mots-clés : human capital,knowledge,development,universities
Projet ERC : GReatLaP (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Mathematics
Entité participante : University of Bonn — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499491.0 €

My objectives consist of laying new foundations for the representation theory of p-adic groups and making significant progress on the local, global and relative Langlands program. The Langlands program is a far-reaching collection of conjectures that relate different areas of mathematics including number theory and representation theory. Work in this area has also lead to the resolution of other major conjectures including Fermat's Last Theorem. A fundamental problem on the representation theory side is the construction of all (irreducible, smooth, complex) representations of certain matrix groups, called p-adic groups. Despite much progress in the past 40 years, we still know surprisingly little about these representations in the general setting. My first main objective is the construction of all (supercuspidal) representations in full generality. This will form the foundation for the future of the representation theory of p-adic groups and have a plethora of applications also beyond this area. Solving this problem will involve tackling all the complications that arise in the non-tame case compared to the tame case. I will then demonstrate the power of this result beyond the representation theory of p-adic groups by making significant contributions to the - global Langlands program. This will be achieved by constructing congruences between automorphic forms based on the existence of enough suitable (omni-)supercuspidal types for p-adic groups. - relative Langlands program. I will prove finite multiplicity of the representations occurring in the space of function on a spherical variety by combining my results about the shape of representations with properties of the moment map. Finally, I will use my insights to advance the explicit local Langlands correspondence by proving that the most-general construction to date, which treats non-singular representations, satisfies all required properties and suggesting a correspondence beyond non-singular representations.

Mots-clés : p adic groups,reductive groups,supercuspidal representations,bushnell  kutzko types,langlands correspondence,automorphic forms,spherical varieties