Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SynthHotSpot (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999953.0 €

The majority of eukaryotes reproduce sexually via meiosis. During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange termed crossover. Meiotic recombination is a major evolutionary force and has a profound effect on patterns of genetic diversity in sexual species. Crossovers distributions are highly non-random and are typically focused in narrow hotspots. Study of hotspots throughout eukaryotes has revealed combinations of genetic and epigenetic factors that contribute to their distributions. In this proposal we will use the extensive genetics and genomics tools available in Arabidopsis to comprehensively dissect hotspot patterning. The strategic aim of the proposal is to use this knowledge to direct de novo hotspots to loci of choice. In the first aim we will use functional genomics to profile the chromosomal distributions of key recombination proteins and test the role of chromatin and higher-order structures in driving these patterns. In the second aim we will study individual hotspots at the fine-scale, to the resolution of individual polymorphisms, using amplification and sequencing of recombinant molecules from gamete DNA. To test genetic versus epigenetic control of hotspots we will use genome-editing to delete hotspot-associated CTT-repeat DNA sequence motifs, in addition to directing DNA methylation in order to epigenetically silence recombination. In the final aim we will use our combined knowledge of hotspot control to implement genome-editing technologies (TALENs & CRISPR-Cas9) during meiosis. This will allow us to rationally control hotspot locations, which will be definitive proof that our models for recombination control are correct. This technology will also accelerate breeding and genome-engineering of our most important crops, where recombination can be limiting. Finally, mapping hotspots will allow us to better understand patterns of natural genetic diversity, including detecting the signatures of selection.

Mots-clés : meiosis,recombination,hotspots,chromatin,genome editing
Projet ERC : MALSWITCH (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Universität Hamburg — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : UHH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

The malaria-causing parasite Plasmodium falciparum has evolved a strategy of clonally variant gene expression to control essential biological processes like antigenic variation and sexual commitment during its persistent blood-stage infection of the human host. Heritable epigenetic silencing of the underlying specialized gene families ensures the limited expression of only a subset of these genes at any time. Switching the expression of individual clonally variant genes enables the parasite to rapidly adapt to changes in its environment, evade the immune system and switch its cell cycle to the development of mosquito-transmissible gametocyte stages. Expression switching of these clonally variant genes therefore represents a key strategy for parasite survival and underlies the evolutionary success of this deadly pathogen. Despite decades of research, the molecular mechanisms coordinating this adaptive gene expression switching are not understood. In my recent research, I developed a unique experimental tool, which for the first time allows the conditional expression switching of endogenous genes in the parasite. I will combine this system with novel CRISPR/Cas derived methodology and proximity-based labelling approaches to deliver the first systematic identification and characterization of the molecular mechanisms controlling epigenetic gene expression switching. The experiments outlined in the proposal will reveal the core of the molecular machinery underlying this fundamental process and elucidate regulatory mechanisms that allow the parasite to translate environmental signals into adaptive switching of clonally variant genes. This will transform our understanding of the molecular mechanisms driving adaptation of this deadly parasite and in the long run might contribute to the design of intervention strategies that P. falciparum is unable to adapt to.

Mots-clés : plasmodium falciparum,clonally variant gene expression,epigenetics,long non coding rna,crispr
Projet ERC : MALSWITCH (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : University of Tübingen — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1434330.0 €

The malaria-causing parasite Plasmodium falciparum has evolved a strategy of clonally variant gene expression to control essential biological processes like antigenic variation and sexual commitment during its persistent blood-stage infection of the human host. Heritable epigenetic silencing of the underlying specialized gene families ensures the limited expression of only a subset of these genes at any time. Switching the expression of individual clonally variant genes enables the parasite to rapidly adapt to changes in its environment, evade the immune system and switch its cell cycle to the development of mosquito-transmissible gametocyte stages. Expression switching of these clonally variant genes therefore represents a key strategy for parasite survival and underlies the evolutionary success of this deadly pathogen. Despite decades of research, the molecular mechanisms coordinating this adaptive gene expression switching are not understood. In my recent research, I developed a unique experimental tool, which for the first time allows the conditional expression switching of endogenous genes in the parasite. I will combine this system with novel CRISPR/Cas derived methodology and proximity-based labelling approaches to deliver the first systematic identification and characterization of the molecular mechanisms controlling epigenetic gene expression switching. The experiments outlined in the proposal will reveal the core of the molecular machinery underlying this fundamental process and elucidate regulatory mechanisms that allow the parasite to translate environmental signals into adaptive switching of clonally variant genes. This will transform our understanding of the molecular mechanisms driving adaptation of this deadly parasite and in the long run might contribute to the design of intervention strategies that P. falciparum is unable to adapt to.

Mots-clés : plasmodium falciparum,clonally variant gene expression,epigenetics,long non coding rna,crispr
Projet ERC : DEVINCI (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

The mammalian neocortex consists of discrete, but highly interconnected, functional areas that collectively encode features of the environment, form associations between stimuli and drive behaviour by transforming sensory input into motor output. All neocortical areas are organised into six layers containing two major classes of neurons, excitatory glutamatergic pyramidal cells and inhibitory GABAergic interneurons. However, each area has distinctive cytoarchitectonical features and inputs that largely determine its computational capabilities. As pyramidal cells comprise the large majority of neurons in the cerebral cortex, much emphasis has been made on their contribution to the differential organisation of cortical areas. In contrast, interneurons have received little attention in the context of the functional specialisation of cortical areas, even though their distribution is highly heterogeneous. The central tenet of this research proposal is that distinct patterns of inhibitory connectivity may accompany, and perhaps even determine, the functional specialisation of neocortical areas. We hypothesise that interneurons play an important role in the tuning of circuits in each cortical area, and therefore that quantitative differences in the relative distribution of specific classes of interneurons, which arise during development, reflect functional specialisations. The overall aim of this research project is to understand how developmental mechanisms ‘sculpting’ the distribution of inhibitory neurons across different neocortical areas contribute to their functional specialisation. This project has the potential to transform our understanding of the organisation of inhibitory circuits in the mammalian neocortex.

Mots-clés : development,diversity,neural circuits,cerebral cortex,interneuron,gaba
Projet ERC : ATLANTIS (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : Norwegian University of Science and Technology — Pays : Norvège — Rôle : PI
Acronyme de l'entité : NTNU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

The marine ecosystem covers around 70% of the planet. Today, every single part of this vast ecosystem is affected by at least one anthropogenic driver of change. This fact should cause us to pause and think: such a huge space, yet habitat and species loss are occurring at an unprecedented rate. The marine ecosystem provides us with a wealth of services and has an economic value exceeding 20 trillion US Dollars. In addition, the marine ecosystem is considered crucial for our sustainable future and is often regarded as the “next economic frontier”. However, despite its importance for humankind, the marine ecosystem is significantly underrepresented in sustainability research. We currently have no holistic approach to quantify the impacts caused by a large number of human pressures in the marine ecosystem. A powerful tool for identifying such impacts is life cycle assessment (LCA). LCA is the best available tool to assess potential environmental impacts of products and processes in a comprehensive way. However, methods have never been properly developed for including marine impacts in LCA results. I will contribute to closing this substantial research gap by developing novel models for quantifying impacts on ecosystem service losses (“whales”), as well as impacts of marine plastic debris (“waste”) and of marine invasive species (“sea walnuts”) within the LCA framework. These models will be developed based on impacts on species richness and ecosystem service potential. Including ecosystem services will be a paradigm extension and a substantial advancement for the LCA framework. All models will be tested in an overarching case study. Currently we are unable to determine whether planned marine activities and processes are sustainable. By developing these models, we will be able to do so with a holistic perspective. This is of unprecedented importance, if we want to manage this vital ecosystem in a sustainable way and preserve it for future generations.

Mots-clés : life cycle assessment  lca,life cycle impact assessment  lcia,marine ecosystem,impact modelling,eosystem services,invasive species,plastic debris
Projet ERC : HyMoCo (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Wuppertal — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : BUW
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1485000.0 €

The meaning of solar energy for future decentralized power supply will largely depend on both efficiency and cost of solar to electrical power conversion. All kinds of conversion strategies including photovoltaics, concentrated solar power, solar to fuel and others would benefit from efficiently collecting solar power on large areas. For this reason luminescent solar concentrators have been developed for over thirty years, but due to waveguide losses their maximum size is still limited to a few centimeters. The proposed project suggests the exploitation of a new type of electromagnetic waveguide in order to realize passive planar concentrators of unsurpassed collection efficiency, size, concentration, lifetime and costs. A dielectric TE1-mode shows a node, a position in the waveguide where no intensity is found. A thin film placed in this node remains largely “invisible” for the propagating mode. Such dielectric node modes (DNMs) have been investigated by the applicant in previous work, but only recently a silver island film (SIF) was for the first time placed in such a node. The resulting extremely low waveguide losses cannot be explained by our current understanding of waveguide modes and hint to a hybridization between the SIF-bound long-range surface plasmon polaritons (LRSPPs) and the DNMs into what we call hybrid node modes (HNMs). The SIFs strongly interact with incident light. An appropriate nanopatterning of SIFs enables efficient excitation of low-loss HNMs modes collecting solar power over square meters and concentrating it. To achieve this goal new technological methods are used that enable patterning on the nanometer scale and low cost roll-to-roll processing at the same time. New measurement techniques and numerical simulation tools will be developed to investigate the HNMs – a novel kind of electromagnetic modes – and their exploitation in the passive solar concentrators.

Mots-clés : solar concentrators,waveguides,nanotransfer printing,silver island films,coalescence control,surface plasmon polaritons,hybrid modes
Projet ERC : MECHANICS (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : University of Göttingen — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : GAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2413250.0 €

The mechanical properties of each of the over 200 cell types in the human body are perfectly well adapted to their function. The large variety of viscoelastic profiles, ranging from soft brain cells to stiff cartilage, and the temporal variability in the mechanical stress response when stationary cells begin to migrate, e.g. in embryogenesis, wound healing or cancer metastasis, is reflected in a surprisingly small number of molecular building blocks. Three distinct filament systems, actin filaments, microtubules and intermediate filaments (IFs), self-organize into a wealth of structural units, collectively termed the cytoskeleton. The main molecular players of this remarkable composite material are largely known. However, from a physics point of view, in particular IFs are poorly understood, despite their importance in health and disease and astonishing mechanical properties, like extreme extensibility and high flexibility. It is not known, how these properties are encoded in the molecular interactions of the protein filament and how they feed into the mechanical behavior of a whole cell. The aim of the proposed research is thus to establish a structure-mechanics-function relationship for this important component of the cytoskeleton. The genetic complexity of the IF protein family with 70 members that are expressed in a tissue specific manner requires a strategic approach involving well-defined model systems and the combination of in vitro and cell work. Direct mechanical testing by applying stress and in situ high-resolution imaging will link mechanical properties to molecular interactions in the hierarchical IF architecture. The results of these in vitro studies will be related to cell experiments to decipher the link between IF type and cell mechanics. The work program will lead to models that predict, how modifications, e.g., in the type of IF protein or specific charge interactions, are associated with changes in cell mechanics and eventually in cell function.

Mots-clés : cytoskeleton,intermediate filaments,mechanical properties,optical trap,confocal imaging,microfluidics
Projet ERC : PoisedLogic (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Spanish National Research Council — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : CSIC
Type d'entité : Recherche
Financement ERC de l'entité : 798094.75 €

The mechanisms that, despite the noisy and stochastic nature of transcription, enable the specific, precise and robust deployment of developmental gene expression programs are poorly understood. We previously identified Poised Enhancers (PEs) as a conserved set of cis-regulatory elements essential for the induction of major anterior neural genes upon ESC differentiation. Importantly, before becoming active in anterior neural progenitors, PEs are already bookmarked in embryonic stem cells (ESC) with unique chromatin and topological features, including binding by polycomb-group protein complexes (PcG) and pre-formed contacts with their target genes. Here I hypothesize that the competence of pluripotent cells to faithfully execute an anterior neural gene expression program is genetically encoded and dependent on the unique modular composition of PEs, consisting of a cluster of highly conserved transcription factor binding sites (TFBS) and a nearby CpG island (CGI). This modular composition might endow PEs with privileged regulatory properties, whereby the TFBS confer cis-activation capacity, while the CGI bestow permissive chromatin and topological features that boost the PEs regulatory activity and increase transcriptional precision. Furthermore, I hypothesize that, together with architectural proteins, this modular composition dictates the specificity, compatibility and responsiveness between PEs and their target genes. Using ESC as a tractable system and genomic, single-cell/single-allele and genetic engineering methods, we will systematically dissect the contribution of each PE module (i.e. TFBS, CGI) and of different epigenetic (e.g. PcG, DNA methylation) and architectural factors (e.g. Cohesin, CTCF) to the regulatory logic of PEs. By systematically dissecting PEs, our work will illuminate novel and general mechanisms whereby enhancer pre-marking facilitates the precise and specific establishment of gene expression programs during vertebrate embryogenesis.

Mots-clés : enhancers,pluripotency,differentiation,transcriptional precision,polycomb,cpg islands,synthetic engineering
Projet ERC : PROGLUTASIS (Horizon 2020, appel 2016, Consolidator 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 : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 2091338.0 €

The metabolic syndrome (MetS) represents one of the major public health challenges worldwide. It reflects a combination of medical disorders that, when occurring together, increase the risk of developing diabetes and cardiovascular disease. The prevalence in the USA is estimated at 30% of the population and the European community follows this trajectory. It is now recognized that the state of chronic low-grade inflammation may favor the onset and progression of the MetS. While the notion of metabolic flexibility in hematopoietic cells has recently emerged in several inflammatory diseases, the origin of this immunometabolic alteration in the MetS remains elusive. There is a growing appreciation that the apportioning of nutrients into different metabolic pathways can support or direct functional immune and hematopoietic changes. Glutamine is the most abundant amino acid in the plasma and an important energy source through glutaminolysis. Despite its potential proliferative and/or immunosuppressive function and the strong association between high glutamine-to-glutamate ratio with cardiometabolic traits, the underlying mechanisms are poorly understood. Thus, there is a considerable therapeutic interest in better understanding the mechanisms linking glutamine to cardiometabolic risks and in particular cardiometabolic inflammation. In PROGLUTASIS, we will investigate the metabolic and immune regulation of glutamine homeostasis in the metabolic syndrome. We will validate the contribution of glutaminolysis in cardiometabolic inflammation, including obesity, diabetes and atherosclerosis through its role on hematopoiesis and macrophage dynamics. Given the ubiquitous association between glutamine and chronic metabolic stress, we expect that identifying the underlying molecular mechanism will offer novel therapeutic perspective on how to intervene in this pathway. This will ultimately allow for tailored strategies aimed at dampening cardiometabolic inflammation in the MetS.

Mots-clés : cardiometabolic diseases,glutamine,glutaminolysis,immunometabolism,low grade inflammation,macrophages,efferocytosis,hematopoiesis,hematopoietic stem cells,proliferation,redox,obesity
Projet ERC : FIRM (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 878105.75 €

The molecular communication between mitochondria and nucleus is an integrated bi-directional crosstalk - anterograde (nucleus to mitochondria) and retrograde (mitochondria to nucleus) signalling pathways. The mitochondrial retrograde response (MRR) is driven by defective mitochondrial function, which increases cytosolic reactive oxygen species (ROS) and Ca2+. Metabolic reprogramming is a key feature in highly proliferative cells to meet the energy needs for rapid growth by generating substrates for cellular biogenesis. In these mitochondria retro-communicate with the nucleus to induce wide-ranging cytoprotective effects exploited to develop resistance against treatment and sustain uncontrolled growth. Recently, the mitochondrial management of cholesterol-derived intermediates for the synthesis of steroids has been demonstrated as a determinant in the oncogenic reprogramming of cellular environment. We hypothesise that cholesterol-enriched domains facilitate the communication between remodelled mitochondria and nucleus to expedite MRR. This mechanism may be exploited during abnormal cell growth in which cholesterol metabolism and associated molecules are increased. This application capitalizes on expertise in cell signalling and metabolism to interrogate core pathways and unveil molecular sensors and effectors that define form and function of the MRR by: I. Elucidating the mechanism of metabolic regulation of MRR, describing the role exerted by cholesterol trafficking; II. Unveiling microdomains for mito-nuclear communication established by remodelled, autophagy escaped, mitochondria; III. Validating protocols to modulate and target MRR for diagnostic and therapeutic benefit; The experimental plan will (i) define a molecular signalling axis that currently stands uncharacterized, (ii) provide mechanistic knowledge for preventive, and (iii) therapeutic applications to counteract deficiencies associated with stressed, dysregulated mitochondria.

Mots-clés : mitochondria,inter organelles communication