Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : FLEXPEPNET (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Acronyme de l'entité : KUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1559807.5 €

Animal brains are wired according to a series of remarkable genetic programs that have evolved over millions of years. Much of our behavior, however, is the product of experiences that happen to us on much shorter time scales. The ability of the nervous system to properly respond to aversive stimuli is crucial for animal well-being and survival. In many vertebrate sensory systems, persistent stimuli are coded by tonically active neural circuits. As opposed to phasic sensors that adapt rapidly, tonic neurons reliably convey stimulus intensity over long time periods and are essential for cues that need to hold attention, e.g. harmful stimuli. How persistent aversive stimuli are molecularly encoded and reprogram behavior remains elusive. Our working hypothesis is that aversive challenge recruits a network of neuropeptide signaling pathways that is sculpted by experience and mediates diverse acute and long-lasting behavioral responses. We will test this hypothesis on the small and well-described oxygen-sensing circuit of C. elegans. Because neuropeptidergic networks are notoriously complex, such a highly controlled context for pioneering research on their involvement in tonic aversive signaling is preferable. First, my team will develop tools for the in vivo reporting of neuropeptide GPCR activation, establishing SPARK in a living animal, which will allow conceptual advancements with unprecedented detail. Pertinent questions we will then address include: ‘How do cellular networks respond to changes in neuropeptidergic network activities in an aversive signaling context?’; ‘What are behavioral implications of neuropeptidergic network activity upon aversive challenge?'; and ‘Do neuropeptidergic networks contribute to cross-modality?' We expect that on the long term, this project will impact our understanding of how tonic peptidergic circuits influence and organize habituation, learning, forgetting and modus operandi of nervous systems in general.

Mots-clés : neuropeptide,g protein coupled receptor,tonic neural signaling,experience dependent plasticity,caenorhabditis elegans
Projet ERC : ALIVEAfrica (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : Swiss Tropical and Public Health Institute — Pays : Suisse — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 216320.31 €

Animals are central to the livelihood strategies of millions of people in sub-Saharan Africa. Across the continent, animals provide sources of food and income, despite the growth of more diverse modes of subsistence. However, entanglements between humans and animals often have deeply problematic consequences for health, well-being and the environment. For example, unsustainable hunting practices reduce biodiversity and risk zoonotic disease transmission, and the uncontrolled use of antibiotics in intensified farming threatens to exacerbate anti-microbial resistance. Meanwhile, against a backdrop of climate-change induced pressures, development projects try to change human-animal relations in order to enhance productivity and economic resilience. Within this emerging dynamic it is important to reappraise the role of animals for contemporary livelihoods; the implications of human-animal relations for the wellbeing of multi-species communities; and the mechanisms of governance that seek to manage human-animal relations. This will be achieved through detailed ethnographic case studies in Kenya and Sierra Leone. This approach will shed light on contemporary livelihood strategies in sub-Saharan Africa. It will enable a major innovation in the social sciences by pushing forward new, post-human, visions for the fields of development and global health. Moreover, these local studies will be situated in a global context through a study of global assemblages of animal-focused development and One Health approaches. A deeper understanding of human-animal relationships has important implications for sustainability across species and will help to shift thinking around health and livelihoods in Africa from an anthropocentric perspective towards a post-humanist vision that enables multi-species stewardship. The project will co-produce knowledge with non-academic partners and build capacity among African scholars to maximise the reach of the research and ensure its long-term legacy.

Mots-clés : health,animals,livelihoods,one health,biomedicine,development,kenya,sierra leone,switzerland
Projet ERC : COLOUR PATTERN (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Collège de France — Pays : France — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1163840.0 €

Animals display a tremendous diversity of patterns ‒from the colourful designs that adorn their body to repeated segmented appendages. Natural patterns result from the formation of discrete domains within developing tissues through the integration of positional cues by cells that consequently adopt specific fates and produce spatial heterogeneity. How can such developmental processes underlie the apparent complexity and diversity of natural patterns? We propose to address this long-standing question with an innovative experimental design: we will make use of natural variation as a powerful tool to facilitate the identification of patterning molecules and morphogenetic events. We will study colour pattern, a crucial adaptive trait that varies extensively in nature, from large colour domains to periodic designs. In amniotes, colour pattern is formed by spatial differences in the distribution of pigment cells and integumentary appendages. While the pigmentation system has been well characterized, the mechanisms governing the formation of compartments in the skin of wild animals have remained unclear, largely because laboratory models do not display ecologically-relevant colour patterns. We will use a combination of forward genetics, developmental biology, modelling, and imaging to study natural variation in the large colour domains of Estrildid finches and the periodic stripes of Galliform birds. For both phenotypes, we will characterize the organization of the embryonic skin and the mode of patterning (i.e., instructional patterning via external cues vs locally-occurring self-organization) underlying their formation, and identify the molecular factors and developmental processes contributing to their variation. Results from these studies will elucidate the biochemical events and tissue rearrangements orchestrating colour patterning in development and shed light on how these processes shape natural variation in this trait‒ and more generally, in natural patterns.
Projet ERC : MicroBeeOme (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Lausanne — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499462.0 €

Animals harbor specialized bacterial communities in their guts, typically referred to as gut microbiomes. Despite the importance of gut microbiomes for host health, surprisingly little is known about their evolution. There is evidence that the complexity of the mammalian gut microbiome has emerged through the diversification of a few founder lineages. However, how lineages have diversified into discrete species and which underlying mechanisms maintain the diversity in the gut remains elusive. The current project will address these questions by studying the gut microbiome of honey bees. We have recently found that the eight dominant bacterial lineages in the honey bee gut have substantially diversified, which is a striking parallelism to the evolution of the mammalian gut microbiome. Moreover, we have established experiments to colonize microbiota-free bees with cultured isolates of divergent bee gut bacteria. This provides us with unique opportunities to study bacterial evolution in the gut in a simple and experimentally amenable system. The project is divided into four work packages addressing interconnected research questions of current biology: We will (i) determine the population genomic landscape of divergent gut bacteria, (ii) investigate whether bacterial diversification has resulted in competition or cooperation, (iii) discover novel mechanisms of bacterial interactions, and (iv) reveal how bacterial diversification impacts the symbiosis with the host. To this end, we will use a multidisciplinary approach combining comparative metagenomics, transcriptomics, metabolomics, bee colonization experiments, microscopy, bacterial genetics, and automated bee tracking. This project situated at the forefront of microbial symbiosis will provide groundbreaking insights into microbial evolution and ecology, gut microbiology, and honey bee health and biology.

Mots-clés : microbial symbiosis,microbial diversity,gut microbiota,metagenomics,honey bee
Projet ERC : FORECASToneMONTH (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Hebrew University of Jerusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1719000.0 €

Anomalies in surface temperatures, winds, and precipitation can significantly alter energy supply and demand, cause flooding, and cripple transportation networks. Better management of these impacts can be achieved by extending the duration of reliable predictions of the atmospheric circulation. Polar stratospheric variability can impact surface weather for well over a month, and this proposed research presents a novel approach towards understanding the fundamentals of how this coupling occurs. Specifically, we are interested in: 1) how predictable are anomalies in the stratospheric circulation? 2) why do only some stratospheric events modify surface weather? and 3) what is the mechanism whereby stratospheric anomalies reach the surface? While this last question may appear academic, several studies indicate that stratosphere-troposphere coupling drives the midlatitude tropospheric response to climate change; therefore, a clearer understanding of the mechanisms will aid in the interpretation of the upcoming changes in the surface climate. I propose a multi-pronged effort aimed at addressing these questions and improving monthly forecasting. First, carefully designed modelling experiments using a novel modelling framework will be used to clarify how, and under what conditions, stratospheric variability couples to tropospheric variability. Second, novel linkages between variability external to the stratospheric polar vortex and the stratospheric polar vortex will be pursued, thus improving our ability to forecast polar vortex variability itself. To these ends, my group will develop 1) an analytic model for Rossby wave propagation on the sphere, and 2) a simplified general circulation model, which captures the essential processes underlying stratosphere-troposphere coupling. By combining output from the new models, observational data, and output from comprehensive climate models, the connections between the stratosphere and surface climate will be elucidated.

Mots-clés : stratosphere troposphere coupling,quasi biennial oscillation,stratospheric polar vortex
Projet ERC : FORECASToneMONTH (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : New York University — Pays : Etats-Unis — Rôle : Partner
Acronyme de l'entité : NYU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 89000.0 €

Anomalies in surface temperatures, winds, and precipitation can significantly alter energy supply and demand, cause flooding, and cripple transportation networks. Better management of these impacts can be achieved by extending the duration of reliable predictions of the atmospheric circulation. Polar stratospheric variability can impact surface weather for well over a month, and this proposed research presents a novel approach towards understanding the fundamentals of how this coupling occurs. Specifically, we are interested in: 1) how predictable are anomalies in the stratospheric circulation? 2) why do only some stratospheric events modify surface weather? and 3) what is the mechanism whereby stratospheric anomalies reach the surface? While this last question may appear academic, several studies indicate that stratosphere-troposphere coupling drives the midlatitude tropospheric response to climate change; therefore, a clearer understanding of the mechanisms will aid in the interpretation of the upcoming changes in the surface climate. I propose a multi-pronged effort aimed at addressing these questions and improving monthly forecasting. First, carefully designed modelling experiments using a novel modelling framework will be used to clarify how, and under what conditions, stratospheric variability couples to tropospheric variability. Second, novel linkages between variability external to the stratospheric polar vortex and the stratospheric polar vortex will be pursued, thus improving our ability to forecast polar vortex variability itself. To these ends, my group will develop 1) an analytic model for Rossby wave propagation on the sphere, and 2) a simplified general circulation model, which captures the essential processes underlying stratosphere-troposphere coupling. By combining output from the new models, observational data, and output from comprehensive climate models, the connections between the stratosphere and surface climate will be elucidated.

Mots-clés : stratosphere troposphere coupling,quasi biennial oscillation,stratospheric polar vortex
Projet ERC : ECHOE (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
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 : 1951250.0 €

Anonymous Old English preaching texts, written and copied between the ninth and late twelfth centuries, survive in ca. 350 versions in ca. 55 manuscripts. They represent the most comprehensive vernacular preaching corpus of medieval Europe before 1200 AD and depend almost entirely on a wide variety of Latin sources from all over the continent. This project will revolutionise scholarly work on Old English anonymous homilies by tracing, visualising, and studying their highly complex material and textual transmission in full. It will recover, unite, and systematise all surviving Old English anonymous homilies (ca. 500,000 words) in an online and interactive digital corpus that brings to the fore the individual manuscript version and all its revisional layers from before 1200. The project counters traditional editorial models of collation by exposing substantial textual difference and by analysing compositional and variational strategies. This will enable users for the first time to comprehensively study Old English anonymous homilies as living texts through the centuries. ECHOE will a) introduce a new taxonomy for the homiletic corpus, b) identify the closest Latin and Old English sources, c) identify the compositional structure of mobile textual units between related versions of the corpus, d) mark up decisive palaeographical features, idiosyncratic diction, formulas, themes, and genres, and e) assess the historical, social, and theological dimension of revisions and the roles of individual revisers in the making of English Christianity. The digital corpus will reveal for the first time the complex network of interrelated versions and allow for a swift in-depth comparison of parallels and their sources. It will further allow modern audiences to explore the chronological as well as geographical relations between Old English homilies and their European sources, and will open up new perspectives on the identity of authors, revisers, users, and audiences.

Mots-clés : old english literature,homiletics,anglo latin literature
Projet ERC : ImmunoFit (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Vlaams Instituut voor Biotechnologie — Pays : Belgique — Rôle : PI
Acronyme de l'entité : VIB
Type d'entité : Recherche
Financement ERC de l'entité : 1999721.0 €

Anti-cancer immunotherapy has provided patients with a promising treatment. Yet, it has also unveiled that the immunosuppressive tumor microenvironment (TME) hampers the efficiency of this therapeutic option and limits its success. The concept that metabolism is able to shape the immune response has gained general acceptance. Nonetheless, little is known on how the metabolic crosstalk between different tumor compartments contributes to the harsh TME and ultimately impairs T cell fitness within the tumor. This proposal aims to decipher which metabolic changes in the TME impede proper anti-tumor immunity. Starting from the meta-analysis of public human datasets, corroborated by metabolomics and transcriptomics data from several mouse tumors, we ranked clinically relevant and altered metabolic pathways that correlate with resistance to immunotherapy. Using a CRISPR/Cas9 platform for their functional in vivo selection, we want to identify cancer cell intrinsic metabolic mediators and, indirectly, distinguish those belonging specifically to the stroma. By means of genetic tools and small molecules, we will modify promising metabolic pathways in cancer cells and stromal cells (particularly in tumor-associated macrophages) to harness tumor immunosuppression. In a mirroring approach, we will apply a similar screening tool on cytotoxic T cells to identify metabolic targets that enhance their fitness under adverse growth conditions. This will allow us to manipulate T cells ex vivo and to therapeutically intervene via adoptive T cell transfer. By analyzing the metabolic network and crosstalk within the tumor, this project will shed light on how metabolism contributes to the immunosuppressive TME and T cell maladaptation. The overall goal is to identify druggable metabolic targets that i) reinforce the intrinsic anti-tumor immune response by breaking immunosuppression and ii) promote T cell function in immunotherapeutic settings by rewiring either the TME or the T cell itself.

Mots-clés : tumor microenvironment
Projet ERC : mARs (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : University of Geneva — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIGE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999118.0 €

Antibiotic resistance (AR) is spreading rapidly, leading to the development of highly virulent pathogens and multidrug-resistant ‘superbugs’, a major health concern of our era. Mobile DNA elements, transposons and integrons, effectively drive the spread of AR genes in microbial interaction hotspots, such as bacterial communities in humans and natural environments. Yet, our knowledge of their mechanisms remains very sparse. It is unclear how DNA movement occurs on the molecular level and how it is controlled in cells and communities; biochemical and structural data are rare and our view on their diversity and evolution is limited. Here I propose an integrated approach combining bioinformatics, genetics, microbiology, biochemistry, and structural biology to elucidate the mechanisms and diversity of mobile DNA driven resistance spreading. I want to (a) investigate the molecular mechanisms and regulation of AR gene movement in vitro, in model bacteria and in gut bacterial communities; (b) dissect the structure of the underlying molecular machineries to reveal how protein-DNA interplay promotes gene transfer; and (c) characterize the diversity, evolution and functional success of distinct molecular pathways. Mechanistic work will focus on selected mobile elements that confer resistance to last resort drugs and promiscuous gene carriers with high prevalence in health care. Bioinformatic quests will draw on recent (meta)genomic data to chart the clinical significance of molecular insights in situ. By bridging disciplines, I want to provide functionally annotated molecular movies of gene movement and explain how specific molecular strategies evolved to enable broad dissemination of resistance determinants. The insights gained in this research will provide in-depth knowledge on major AR transfer pathways and will have key implications for the development of novel intervention strategies and preventive measures aimed at reducing dissemination of drug resistance in bacteria.

Mots-clés : mobile genetic elements,multi drug resistant bacteria,antibiotic resistance transmission,gene transfer,molecular mechanism,microbiome
Projet ERC : NO-ESKAPE (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Utrecht University — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 215958.75 €

Antibiotic resistance poses an alarming threat to global health. Most worrisome are the so-called “ESKAPE” pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa, and Enterobacter species), a collection of organisms capable of escaping the effects of almost all conventional antibiotics. Key to combating drug-resistant bacteria is the identification of new antibacterial targets and the ability to exploit these targets with novel and unconventional antibiotics. The microbial world produces a wealth of antibacterial compounds that, while not suitable for therapeutic use, operate by diverse and unique modes of action. This proposal describes innovative approaches aimed at the discovery and development of such compounds as leads towards novel antibiotics with entirely new modes of action. Using a multidisciplinary approach, firmly grounded in synthetic organic chemistry, I will prepare and validate new antibiotics that target the ESKAPE pathogens by exploiting mechanisms critical to their survival and/or resistance. To tackle the Gram-positive ESKAPE pathogens a number of new approaches to interfering with bacterial cell wall biosynthesis will be examined. Specifically, novel (semi)synthetic compounds capable of binding to and sequestering various bacterial cell wall precursors will be prepared and their antibiotic activity assessed. To address the Gram-negative ESKAPE pathogens, inhibitors of the metallo-beta-lactamase enzymes responsible for much of their antibiotic resistance will be pursued. These inhibitors will be achieved via a combination of rational design strategies and innovative natural product screening approaches. The 21st century threat of a post-antibiotic era makes clear the need for innovation in antibacterial drug discovery. The strategies outlined in this proposal address this threat head-on with the aim of delivering valuable lead compounds in pursuit of novel antibiotics.

Mots-clés : antibiotics,semi synthesis,peptides,natural products,bacterial cell wall,metallo beta lactamase inhibitors,mechanism of action,antibacterial assays,resistance assays,enzyme assays