Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : BeePath (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Exeter — Pays : Royaume-Uni — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 141751.0 €

The emergence of novel transmission routes is likely to have profound impacts on the ecology and evolution of infectious diseases, with potentially dramatic effects on host populations. This might be particularly drastic when transmission changes from direct to vector-borne transmission, where prevalence and virulence are expected to increase. Despite its importance for disease control, we lack empirical and theoretical understanding of this process. The emergence of Varroa destructor in honeybees provides a unique opportunity to study how a novel vector affects pathogen ecology and evolution: this ectoparasitic mite is a novel vector for Deformed Wing Virus (DWV), a disease linked to severe increases in hive mortality. To study the fundamental evolutionary ecology of emerging vector-borne diseases, I will exploit a unique natural experiment, the presence of Varroa-free island refugia, to test how this novel vector affects epidemiology and evolution in the field. I will adapt cutting-edge single molecule sequencing to guide controlled lab experiments by viral evolution in the wild, establishing novel reverse genetics approaches in DWV to test causal links between phenotypic and molecular evolution. Like all emerging diseases, DWV is a multi-host pathogen that also infects wild bee species not infested by Varroa, such as bumblebees. This raises an additional question, highly relevant for zoonotic diseases: does this specialist honeybee vector impact disease in wild bee populations? I will model the impact of vector acquisition and evolving pathogens on host populations and test potential prevention and mitigation strategies to safeguard these crucial pollinators. This system will not only provide fundamental insights into the evolutionary ecology of disease, but is also of immediate applied importance: bees are key pollinators of crops and wildflowers, and halting population declines facilitated by infectious disease is crucial for food security and biodiversity.

Mots-clés : vector,transmission,virulence,emerging diseases,pollinators
Projet ERC : ChromTrace (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut Curie — Pays : France — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 216000.0 €

The emergence of resistance to chemotherapy and targeted therapies is a major challenge for the treatment of cancer. While several genetic mechanisms driving resistance processes have been discovered, non-genetic mechanisms have also been shown to contribute to drug resistance. Yet, our restricted understanding of epigenetic evolution has so far limited our ability to modulate resistance using epigenetic modifiers. With ChromTrace, our goal is to reconstruct and define the contribution of epigenetic evolution to chemo-resistance in triple-negative breast tumors. In this aggressive sub-type of breast cancer, chemotherapy is the standard of care, but chemo-resistance remains the major unmet clinical need. We will explore the heterogeneity of H3K27me3chromatin states - key determinant of cell identity - in tumor cells, study how they are transmitted and determine whether they are associated to the resistance phenotype. Combining lineage tracing and targeted sequencing to our original single-cell chromatin profiling approach, we will reconstruct the dynamics of chromatin features over time in the context of genetic evolution. In parallel, using a live-cell microscopy reporter system, we will evaluate the association of recurrent chromatin features with the resistance phenotype and elucidate mechanisms of epigenetic tumor evolution. Our results on the heritability and plasticity of chromatin landscapes will have strong impact on our understanding of epigenetic evolution in cancer. Our long-term goal is to build on this integrated appreciation of molecular tumor evolution processes to propose novel therapeutic strategies to control resistance to chemotherapy. Finally, our approaches being applicable to any dynamic biological system, ChromTrace opens the perspective to study evolution of chromatin landscapes not only in other types of cancer and disease, but also during normal development.

Mots-clés : epigenetics,heritability,plasticity,breast cancer,chemotherapy,single cell chromatin immuno precipitation
Projet ERC : NOVEL (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : Université de Lille — Pays : France — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 117375.0 €

The emerging field of systems biology is revealing the intricate nature of biological organisms, whereby a large fraction of their individual components (genes, proteins, regulatory elements) interact with several others. The co-evolutionary processes that this entails raises the question of how phenotypic novelty may arise in the course of evolution, since all parts of the system have to evolve in a coordinated manner if the phenotype is to remain functional. For most biological systems, however, we are lacking even basic insight into the fine-scale mechanistic constraints and the underlying ecological context. In this project, we will focus on the sporophytic self-incompatibility system in outcrossing Arabidopsis species, a model biological system in which two distinct co-evolutionary processes are becoming well-understood: 1) between the male and female reproductive proteins allowing self-pollen recognition and rejection and 2) between small non-coding RNAs and their target sites that jointly control the dominance/recessivity interactions between self-incompatibility alleles. By studying these two model systems, we will aim to catch the emergence of functional and regulatory novelty in flagrante delicto. We will take a multidisciplinary approach combining theoretical and empirical population genetics, evolutionary genomics and ancestral protein resurrection using transgenic plants. Our goal is threefold: 1) decrypt the molecular alphabet of the interaction between co-evolving nucleotide sequences, 2) predict and evaluate the fitness landscapes upon which the two co-evolutionary processes are taking place and 3) exploit natural variation in closely related species to unveil the kind of co-evolutionary process in natural populations. Our combination of various powerful approaches in a tractable model system should provide insight on diversification, a poorly understood but fundamental evolutionary process that is taking place at all levels of organization.

Mots-clés : plant genomics,self incompatibility
Projet ERC : BacterialCORE (Horizon 2020, appel 2018, Synergy grants)
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 : 546055.0 €

The enormous versatility of bacteria enables the formation of multi-species communities that colonize nearly every niche on earth, making them the dominant life form and a major component of the biomass. Exchange of molecular information among neighboring bacteria in such communities, as well as between bacteria and proximal eukaryotic cells, is key for bacterial success. Yet, the principles controlling these multicellular interactions are poorly defined. Here we describe the identification of a bacterial protein complex, herein termed CORE, whose function is to traffic cytoplasmic molecules among different bacterial species, and between pathogenic bacteria and their human host cells. The CORE is composed of five membrane proteins, highly conserved across the entire bacterial kingdom, providing a ubiquitous platform that facilitates both intra- and inter-kingdom crosstalk. Our preliminary data support the idea that the CORE acts as a shared module for the assembly of larger apparatuses, executing this universal molecular flow among organisms. We propose to elucidate components, structure and biogenesis of the CORE machinery, operating during bacteria-bacteria and pathogen-host interactions. We further aim to provide an unbiased-global view of the extent and identity of cytoplasmic molecules traded via CORE including metabolites, proteins and RNA, and to reveal the criteria determining the specificity of the transported cargo. Furthermore, we intend to decipher the impact of CORE-mediated molecular exchange on bacterial physiology and virulence, and devise anti-CORE compounds to combat pathogenic bacteria. This study is expected to transform the way we currently view bacterial communities and host-pathogen interactions. We anticipate these findings to lead to the development of creative strategies to modulate, predict and even design bacterial communities, and lay the foundation for new and innovative approaches to fight bacterial diseases.

Mots-clés : bacteriology,bacterial host interaction,injectisome,flagella,enteropathogenic e  coli,bacterial infection,bacterial communities,bacterial interspecies interaction,epec
Projet ERC : MADMICS (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Kiel University — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : CAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

The epithelial surfaces are frequently affected by harsh encounters, thus it is not surprising that most cancers originate here. Several chronic bacterial infections have been implicated in human cancers, with Helicobacter pylori (Hp) representing the paradigm of a cancer-inducing bacterium. The gastric pathology of infection tends to progress from mild symptoms, via active gastritis, atrophy, gastric intestinal metaplasia (GIM) and dysplasia towards gastric adenocarcinoma. Intriguingly, GIM is usually cleared of Hp, suggesting this pathological state is not merely an intermediate stage towards cancer development, but can be viewed as a process of adaptive defence. Mutations in the tumor suppressor gene TP53 are frequent events of epithelial malignancy in numerous tissues. Based on compelling evidence from an analysis of congenic mutant organoids and related observations, I pursue the hypothesis that pre-malignant mutations in the epithelium arise as an adaptive response to persistent infections and thus constitute a novel layer of antimicrobial defence and tissue protection. MADMICs will have its main focus on the mutational and epigenetic changes associated with GIM and also touch comparable mucosal pathologies investigated by the PI in recent years. An apparent hallmark of such persistent bacterial infections and related cancers is their link to the function of tumor suppressor p53. MADMICs will capitalize on the PI’s profound experience with pathogens, primary cell culture and chronic infection models. Organoids from normal and premalignant human tissues and isogenic mutant organoids created via CRISPR/Cas9 will be used to explore host cell signaling and mutator pathways with regard to early cancer mutations and their antimicrobial effects. The study will illuminate an unprecedented mechanism of microbial defence from a number of perspectives and likely lead to a paradigm shift of our view on the link between adaptive host responses and early cancer mutations.

Mots-clés : helicobacter pylori,adaptive antimicrobial mutations,tp53,cancer
Projet ERC : uCARE (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : European Molecular Biology Laboratory — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : EMBL
Type d'entité : Recherche
Financement ERC de l'entité : 1986004.0 €

The evolution and spread of antibiotic resistance has become a public health concern of the utmost severity, making once treatable diseases deadly again and undermining our living standards. New therapies are imperative, but equally important are the understanding of the full repertoire of drivers of antibiotic resistance and the identification of ways to counteract them. We have recently established that ~250 non-antibiotic drugs have direct, strong and often broad antibacterial effects on human gut microbes. Moreover, preliminary data indicate that bacteria use similar general resistance mechanisms against both drugs with human targets and antibiotics. This implies that polypharmacy may be a hitherto unnoticed driver of antibiotic resistance. We will use chemical genetics and experimental evolution to systematically map the cross-resistance between human-targeted drugs and antibiotics, and elucidate underlying resistance mechanisms. Using these data, we will next seek to identify antidotes for the antimicrobial side-effects of non-antibiotic drugs, and exploit human-targeted drugs for reverting existing antibiotic resistance. At the genetic level, we will use high-throughput reverse genetics to expose the Achilles heels of bacterial cellular networks for resistance development. Finally, we will uncover the antimicrobial mode of action of tens of human-targeted drugs using thermal proteome profiling and chemical genetics. Together with the genetic information, this line of research will yield design principles and possibly new drug candidates for longer-lived, resistance-proof drug combinations. Overall, this project aims at improving our fundamental biological understanding of antibiotic resistance and the paths to prevent, delay or revert it. It can also set the basis for revisiting current medication policies. The derived principles are likely to be relevant to other diseases and therapies, in which resistance development is an issue.

Mots-clés : reverse genetics,chemical genetics,antibiotic resistance,microbiome,drug combinations,genetic interactions
Projet ERC : DoRES (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1495479.0 €

The evolution of the universe has left an imprint in the form of the chemical elements. Understanding the cosmic origins of the elements remains a major challenge for science. The abundances of elements we see in our solar system, distant stars, meteorites, and in stellar explosions provide us with clues about how the elements came to be produced in a variety of different processes and stellar environments. To unravel these mysteries we need to understand the nuclear reactions producing and destroying the elements. New generation accelerator facilities and instrumentation are being developed in Europe which will enable many of these reactions to be measured directly for the first time, and with high precision. This offers the prospect of a major step forward in the field in the next few years. Many of the key reactions involve unstable nuclei, studied experimentally either by using radioactive beams or targets. These unstable nuclei play a critical role in high temperature stellar environments, most notably stellar explosions. Reactions can occur on the unstable nucleus before it has decayed thereby strongly altering the path of subsequent element synthesis. The proposal is sub-divided into 5 themes, concerning production of the heavy elements in neutron capture reactions, destruction of the cosmic gamma-ray emitter 26Al in core collapse supernovae, neutron source reactions in stars, the puzzle of high abundances of proton-rich heavy isotopes, and the origin of nature’s least abundant isotope 180mTa. Experiments will initially be performed using neutron beams from the upgraded n_TOF facility at CERN including the high flux EAR-2 beam line, and using radioactive beams from the upgraded HIE-ISOLDE facility at CERN. In the later phase of the proposal experiments will also be performed using the new ultra-high intensity neutron beam facility FRANZ at Frankfurt, and with radioactive beams injected into heavy ion storage rings to be installed at GSI and CERN.
Projet ERC : ECOLBEH (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Zurich — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UZH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1075738.0 €

The evolutionary transition from solitary to group living has fundamentally changed how organisms interact with their environment. However, to reap the rewards of group living, from collective intelligence to predator avoidance, group members must maintain cohesion by making collective decisions. Theory suggests that individuals’ ability to influence collective decisions could be determined by a range of factors, including their state, social role, relationships with other group members, the composition of their social group, and the physical environment. Although these factors could all interact, most empirical studies have investigated them in isolation. The aim of this project is to take a ‘whole-system’ approach by quantifying (1) how individual-level factors determine leadership, (2) how movement decisions are modulated by long-term social and genetic relationships among group members, and (3) whether the mechanisms by which groups reach consensus are resilient to rapid environmental change. This research program will add unprecedented ecological validity and replication to the field of collective decision making. I will leverage state-of-the-art technology and develop novel methods to simultaneously collect and analyse multi-scale data in a wild population of highly social birds. These data include the movement of individuals within and between groups (high-resolution GPS), social interactions (direct observations), kinship (whole-genome sequencing), physiology (heart rate), and environmental conditions (drone-based mapping). The analytical methods I will develop (e.g. multi-layered dynamic social network analysis) will provide new tools for the research community, while integrating these unique data across replicated groups and over multiple generations, the project will bring new depth to the field. This depth is essential to address the questions that are central to our understanding of social behaviour in mobile animal groups, including humans.

Mots-clés : social behaviour,collective decision making,social network analysis,animal behaviour,movement,ecological conditions
Projet ERC : NEDM (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Université Grenoble Alpes — Pays : France — Rôle : PI
Acronyme de l'entité : UGA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1409796.25 €

The existence of a permanent electric dipole moment (EDM) of the neutron, or any subatomic particle, would have far reaching implications connecting particle physics with cosmology. Time reversal invariance and CP symmetry would be violated. A new fundamental interaction producing the EDM, that is, deforming the charge distribution inside the neutron, could also have generated the matter-antimatter asymmetry in the early Universe. After 60 years of evolution, techniques to measure the neutron EDM are now so evolved that experiments are sensitive to microphysics associated with an energy scale beyond that accessible at the LHC. This situation offers a high likelihood of discovery for the next generation of experiments. In the same time, any improvement in precision is technically challenging. The control of the magnetic field must surpass that of the state of the art of atomic magnetometers. The n2EDM project aims at improving the precision by an order of magnitude or more. Systematic effects need to be controlled at an unprecedented level. In particular, the use of a mercury co-magnetometer based on the precession of 199Hg spins induces a set of subtle false effects due to the relativistic motional field. I propose to initiate a comprehensive program to master these systematic effects beyond the current research program. In particular, the proposed project includes a precise determination of the 199Hg magnetic moment with a precision of 0.1 ppm. To this end, I will attempt a novel approach: combining mercury and 4He magnetometry in the same cell. As a by-product, this will also produce an improved determination of the neutron magnetic moment, a quantity of interest for metrology. The cross-check I propose will prove that all disturbances on the neutron or mercury spins are mastered at the sub-ppm level, a decisive step in the quest for the neutron EDM.

Mots-clés : baryogenesis
Projet ERC : WEB DATA OPP (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Social World and Its Diversity
Entité participante : CERCA Institution — Pays : Espagne — Rôle : PI
Acronyme de l'entité : CERCA;I-CERCA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 233852.5 €

The expansion of the Internet and the development of a range of new active and passive measurement tools, particularly on mobile devices, present exciting opportunities for survey researchers, such as visual or geolocation data capture. Using these new measurement opportunities could reduce respondent burden, improve data quality, and extend measurement into new domains, allowing to answer questions that could not be answered so far and to improve the decisions of key actors (e.g. government). This could open the door to a whole range of completely groundbreaking research, providing new knowledge, and affecting key aspects of our societies. While many people speak about these ideas, very little research has implemented such possibilities, and even less has assessed the data quality associated with such approaches. Thus, there is a huge need for further research in this area. The main goal of this project is to investigate how some of these new measurement opportunities that the growing presence of mobile devices made possible can help scientists and practitioners to get more accurate and/or more complete insights, by addressing three crucial research questions: 1. Can we improve (mobile) web survey data quality by using new measurement opportunities? 2. Can we replace part of the (mobile) web survey data by using new measurement opportunities? 3. Can we achieve a more complete picture of the reality by combining new measurement opportunities with (mobile) web survey data? This project will focus on four new measurement opportunities: voice input, visual data, metered data, and in-the-moment surveys. It will present theoretical and practical outputs, developing the technical tools for making these measurements possible and easy to implement in (mobile) web surveys, as well as a general framework that can be used by practitioners and researchers. The methods developed will be illustrated by answering key applied questions in different areas (e.g. health or politics).

Mots-clés : web data,passive data,mobile devices,smartphones,surveys,measurement,data quality,accuracy of results,voice recording,visual data,in the moment  surveys,metered data,framework