Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PATHOCOM (Horizon 2020, appel 2020, Synergy grants)
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : CO-PI
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 2742525.0 €

Infectious disease is often the major selective agent in nature, and we cannot understand how populations evolve without understanding their pathogenic microbes. Beyond host immunity, an important factor determining the ability of pathogens to invade and proliferate in a host is the resident microbiota, but we are only beginning to glimpse its multifarious impacts. We know even less about interactions among pathogenic microbes themselves. Any effort to explain how pathogen communities, or pathobiota, develop within a host requires knowledge about the extent to which pathogens engage in competition, commensalism and cooperation, both with other pathogens and the rest of the microbiota. To date, studies of plant-pathogen interactions in the lab and descriptive work in the field have focused on pairwise interactions between one plant host and one pathogen, leaving a large gap in our understanding of how different types of interactions between microbes, and especially pathogens, determine the outcome of host-pathogen interactions in the real world. In PATHOCOM, we will implement a program that integrates large-scale field observations of microbes in the plant Arabidopsis thaliana with ultra-high-throughput experimental tests of host-dependent interactions among microbes, allowing experiment-informed modeling of pathogenic microbe-microbe interactions. These models, which will be improved through an iterative process of data collection with synthetic communities, will illuminate how interactions, from pairwise to higher-order, shape microbial community composition and structure. In the final step, the resulting models will be tested against and refined with field data. Together, these efforts will transform the study of plant pathogens by applying deep analyses of microbial interactions in an ecological context to explain patterns in nature. Ultimately, PATHOCOM will play an essential role in refashioning plant-pathogen-microbiome studies into a predictive science.

Mots-clés : arabidopsis thaliana,ecological genomics,pathogen pathogen interactions,host microbiota interactions,ecology community structure,community modeling
Projet ERC : ART-HEALTH (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Bristol — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499951.0 €

Infertility affects 1 in 6 couples. With increasing numbers of artificial reproductive technology (ART) conceptions, understanding the effects of ART on maternal and offspring health has been designated a major research priority. Research to date has been highlighted as having limited quality and lacking methodological transparency. In ART-HEALTH we use a robust, systematic approach of triangulating different sources of evidence to address this. work-package (WP) 1 will generate three new datasets with complementary sources of bias. 1. Birth cohort collaboration of 360,000 spontaneously conceived (SC) and 10,000 ART offspring. This will provide rich data on large numbers with ART offspring recruited, assessed and followed in identical ways to SC offspring. 2. Large ART cohort (5000 couples) with detailed information on treatments linked to a SC group that will have identical data collected from pregnancy to mid-childhood. 3. Large population record linkage of 200,000 contemporary ART births, 10,000 of their SC siblings and 400,000 general population SC births. WP2 will triangulate evidence to determine the effects of ART on perinatal and offspring cardiometabolic health. It will compare results from the 3 datasets and updated systematic reviews, using conventional multivariable regression and within sibship analyses. WP3 will analyse the datasets using Mendelian randomization, and multivariable regression in a counterfactual framework to explore pregnancy metabolomic mediation. We will systematically and transparently assess risk of bias with each analytical method in each dataset and use bounds of causality and Bayesian approaches to integrate data. PhD students, funded from elsewhere, will explore effects on parental and offspring mental health and cognitive function. In the final year we will work with colleagues in Brazil, Pakistan, a- ART is increasing - Concerns about effects - Evidence base limited - Our objectives - Why these will make a difference

Mots-clés : artificial reproductive technologies,perinatal health,cardiometabolic health,causal inference,triangulation
Projet ERC : MicroRepro (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Chemnitz University of Technology — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1975749.07 €

Infertility is a health issue with sociological and psychological implications that affects approximately 50 million couples worldwide and therefore receives global attention. Among fertility issues, male infertility is diagnosed in about 40% of all cases and the major causes are poor motility of spermatozoa (asthenospermia), low sperm count (oligospermia), abnormal sperm morphology (teratospermia) and/or combinations of these, leading to their inability to fertilize an oocyte. Such problems have been mainly addressed by artificial insemination (AI) and in vitro fertilization (IVF). AI involves introducing sperms into a woman’s uterus with a medical instrument, but its applicability is limited and its success rate is below 30%. In contrast, IVF and intracytoplasmic sperm injection can be more effective but implicate more invasive procedures such as removing oocytes from a woman’s ovaries, fertilize them outside of the body and then transfer the embryos back to the uterus a few days later. These difficulties demand rethinking of assisted fertilization and the sought after novel approaches that offer more natural procedures with high success rate. Hence, we propose untethered medical microbots to assist sperm cells to fertilize an oocyte in living organisms (mice model). The MicroRepro project will bring advances in areas such as bioimaging, nanomaterials science and fundamental biology, boosting the whole field of medical microbots in the process, as was recently highlighted by the PI in an extended comment [Nature 545, 406(2017)]. The PI has decisively contributed to the field of microrobotics and invented the sperm-robot (Spermbot) concept together with his team in two previous patent applications and several publications. The mere concept has attracted worldwide attention. However, even in vitro fertilization has never been achieved – therefore, targeting the challenges leading to the first spermbot fertilization will be the main objective of this project.

Mots-clés : in vitro fertilisation,micromotors,microrobotics,deep tissue imaging,nanomedicine
Projet ERC : INFLAME (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
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 : 1498799.0 €

Inflammasomes are intracellular multi-protein complexes that play essential functions in immunity against microbial pathogens. Upon microbial sensing, inflammasomes induce protease caspase-1-dependent maturation and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 as well as gasdermin-D-dependent cell necrosis, namely pyroptosis. While both pyroptosis and IL-1β/IL-18 release play key parts in controlling microbial infections, the host-regulated pathways that promote detection of microbial ligands by cytosolic inflammasome-forming sensors and the non-canonical functions of inflammasome-derived components, remain to be fully characterized. Building on my expertise in the field of inflammasome regulators during microbial infections, I propose to study several key, yet unexplored aspects of the functions of inflammasomes in immunity from different angles. In particular, I propose to 1/ identify and characterize new host interferon-inducible factors that mediate microbial sensing by the inflammasomes, and 2/ unravel new non-canonical functions of inflammasome-derived proteases and gasdermins. To address these issues, I will use a combination of state-of-the-art and innovative technologies in biochemistry, molecular and cell biology, and immunology in various in vitro and in vivo models. For example, I propose to develop an unbiased genome-wide search for novel effectors involved in inflammasome activation based on the unprecedented coupling of the CRISPR-Cas9 technology to automated visual high-throughput screening. This multidisciplinary proposal will provide breakthroughs in the field of microbial pathogens detection by the host immune system, and will nucleate entirely novel immune paradigms on microbial sensing by new unsuspected host cytosolic proteins, namely the gasdermins. The results of this project will also provide strong bases for building innovative host-directed therapies for auto-inflammatory disorders and infectious diseases.

Mots-clés : inflammasomes,cell death,microbial sensing,gasdermins,alarmins,proteases
Projet ERC : DESTRESS (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Trinity College Dublin — Pays : Irlande — Rôle : PI
Acronyme de l'entité : TCD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499386.25 €

Inflammation is initiated in response to the detection of foreign entities, called PAMPs derived from infectious agents, or due to the release of intracellular contents, called DAMPs, due to serious tissue damage (i.e. necrosis). However, inflammation can also be initiated in response to Cell Stress (e.g. ER stress, cytoplasmic stress, mitochondrial stress) resulting from perturbations in normal physiology, but how cellular stress is converted to inflammatory outputs is very poorly understood. Many diseases are associated with chronic long-term inflammation (e.g. cancer, obesity, neurodegeneration, diabetes), which is a compounding factor in these conditions that can accelerate disease progression, but the inflammation seen in these conditions does not have an obvious infectious (PAMP) or acute injury (DAMP) cause. Instead, these diseases are frequently associated with persistent cell/tissue stress (e.g. due to misfolded proteins, elevated dietary fats, or metabolic stress) arising from persistent ER or cytoplasmic stress, that is likely to serve as a key driver of inflammation in these settings. However, the key sensors and effectors of stress-induced inflammation remain enigmatic. Based on our recent observations, I wish to explore the hypothesis that members of the 'Death Receptor' subset of the TNF receptor family serve as stress-associated molecular patterns (SAMPs), becoming upregulated and/or activated in response to divergent forms of ER and cytoplasmic stress, leading to inflammation. Here, we will explore the role of Death Receptors as putative SAMPs, how they are activated by stress, the composition of their stress-induced signaling complexes, and the potential to suppress stress-induced inflammation through targeting these receptors. Understanding how Cell Stress initiates inflammation will open up a new frontier in inflammation research and identify new molecular targets for the treatment of chronic inflammation associated with multiple diseases.

Mots-clés : inflammation,death receptors,cell stress,er stress,tnf receptor family,trail receptor
Projet ERC : IBDIMAGE (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Edinburgh — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Inflammatory bowel diseases (IBD) are chronic immune-mediated disorders causing inflammation of the gastrointestinal tract, which affect around 3 million patients in the EU. Current monitoring of IBD is mainly performed in the form of colonoscopies, biopsies or tests which are invasive or cannot specifically report on IBD activity. There is a need for new technologies that can rapidly measure activity biomarkers of IBD and enable the monitoring of disease progression and response to therapy accurately. This unmet patient need is what drives the development of this ERC PoC project. The ERC CoG DYNAFLUORS (Dynamic Activatable Fluorophores) project was funded to develop the first chemical toolbox for imaging the activity of immune cells in real time. In IBD, the activity of immune cells are important indicators of the disease state and can be used to assess how patients respond to therapy. DYNAFLUORS measure real-time immune cell activity; hence they are optimal tools to monitor disease progression in IBD patients facilitating a more accurate and personalised therapeutic approach. Based on our promising results in the ERC CoG, we aim to develop DYNAFLUORS into a new fluorescent technology for imaging IBD activity which will lead to: 1) new tools for IBD research and drug discovery in collaboration with companies covering the global fluorescent reagent market as well as Pharma, and 2) point-of-care technologies for clinical diagnostics in IBD patients. Funding from the ERC PoC will allow us to commercialise fluorescent reagents for research, in vitro diagnostics and drug discovery as well as to establish the foundations for new translational technologies to measure IBD activity in patients. This project will be guided by input from existing and new industrial and clinical partners and will create numerous opportunities for accelerating the research, diagnosis and treatment of IBD.

Mots-clés : fluorescent probes,peptides,fluorophores,inflammation,immunology,diagnostics
Projet ERC : LeukoTheranostics (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2527608.0 €

Inflammatory bowel diseases (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease (CD) and Ulcerative Colitis (UC) that can impact both the large and small bowel. IBD affects approximately 3.7 million Europeans and its peak onset is in persons of 15 to 30 years of age. IBD imposes a significant burden on Europe with over €3B in annual health care costs and over €3B in indirect cost. The prevalence of IBD is expected to increase by more than 40% over the next decade in many European countries. Therefore, to meet the needs of IBD patients in the European community, we must prepare for the evolving landscape of IBD care in the near future. Although its etiology remains unknown, unregulated immune cells are implicated in the pathogenesis of IBD. As many IBD patients are refractory to conventional medical treatments, there is an urgent need to develop novel therapeutic modalities in combination with real-time imaging in order to manage the disease. I will achieve this goal by generating a "Trojan horse" strategy of targeting activated leukocytes that home to the gut in IBD rodent models and reprogram their fate using RNA interference (RNAi) combined with molecular imaging. The primary objective of this proposal is to reprogram in vivo activated leukocytes involved in gut inflammation using advanced RNAi-based therapeutics combined with molecular imaging strategies as the first theranostic modality utilizing leukocytes. The following specific aims include: (i) To develop and characterize unique integrin-targeted nanoparticles (I-tsNPs) targeting a high-affinity (HA) conformation of a4b7 integrin expressed on gut leukocytes; (ii) To study I-tsNPs 3-dimensional (3-D) delivery in colitis models using microPET/CT imaging; (iii) To investigate efficacy and safety profiles using the HA I-tsNPs platform for IBD therapeutics and disease management that will lay the foundation for future clinical trials.

Mots-clés : sirna,nanomedicine,leukocytes,integrins
Projet ERC : IMEDMC (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : Fondation nationale des sciences politiques — Pays : France — Rôle : PI
Acronyme de l'entité : FNSP
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1372381.0 €

Informational environments are largely endogenous. They can be, and often are, chosen or designed by individuals or organizations with specific objectives in mind. As recognized by a large literature in economics, information plays a crucial role in shaping the outcome of downstream decisions by strategic players (i.e. at the receiving end of informative signals). However, the structure of information also impacts decisions by strategic agents upstream of the generation of signals, as agents mould the underlying reality differently depending on how other players will eventually be informed about it. Finally, designed information production systems are susceptible to manipulations by third party agents pursuing their own interests. I will seek to further our understanding of socially or privately optimal information designs, how they shape upstream and downstream decisions, how they can be manipulated by private interests, and how to best anticipate and counter such manipulations. I will rely on the analysis of a largely unexplored designer-agent-receiver class of games, in which the designer picks an information generation system, the agent takes an upstream decision affecting the states of the world, or manipulates the production of information, and receivers choose downstream actions based on realized signals. The project is organized around the different technologies available to the agent. I will consider fake news production, which is the fabrication of signals that pass as informative but are in fact independent of the truth; state falsification, which consists in falsifying the state of the world, or feeding the information production process with falsified data; pure agency, which is the possibility for the agent to secretly deviate to a different but undistinguishable information generation technology; and state shifting, which is the upstream effort an agent can exert to actually transform the probability distribution of states of the world.

Mots-clés : information design,persuasion,fake news,falsification
Projet ERC : EYEGET (Horizon 2020, appel 2015, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Innovavector srl — Pays : Italie — Rôle : Partner
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 50000.0 €

Inherited retinal degenerations (IRDs) are a major cause of blindness worldwide. IRD patients witness inexorable progressive vision loss as no therapy is currently available. In the last decade my group has significantly contributed to a change of this scenario by developing efficient adeno-associated viral (AAV) vectors for retinal gene therapy that are safe and effective in humans. The objective of EYEGET (EYE GEne Therapy) is to overcome some of the current major limitations in the field of retinal gene therapy to expand initial therapeutic successes to a larger number of IRDs. To achieve this, we propose to use four parallel, highly innovative and complementary approaches: i. expansion of the limited AAV cargo capacity by a novel methodology based on co-administration of multiple AAVs that reassemble in target retinal cells and reconstitute large genes; ii. targeting of frequent dominant gain-of-function mutations that cause RP using state-of-the-art AAV-mediated genome editing technologies; iii. induction of retinal cells clearance of toxic IRD products by AAV-mediated activation of autophagy and lysosomal function; iv. development of methodologies to directly convert fibroblasts to photoreceptors that can be transplanted in retinas from IRD patients with advanced PR loss and for whom in vivo gene therapy is no longer an option. We will use a combination of in vitro and in vivo state-of-the-art technologies including novel AAV vector design, high content screening of drugs that enhance AAV transduction, genome editing, and advanced in vivo retinal phenotyping to obtain proof-of-concept for each of these therapeutic strategies. The results from this study may impact the quality of life of millions of people worldwide by providing a cure based on gene and/or cell therapy for a large group of IRDs.

Mots-clés : retina,inherited retinal degenerations
Projet ERC : IniReg (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Max Planck Society — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : MPG
Type d'entité : Recherche
Financement ERC de l'entité : 192455.79 €

Injury poses a key threat to all multicellular organisms. However, while some animals can fully restore lost body parts, others can only prevent further damage by mere wound healing. Which molecular mechanisms determine whether regeneration is induced or not is an unsettled fundamental question. I will use whole body regeneration, one of the most fascinating biological processes, as an experimental paradigm to identify the mechanisms of regeneration initiation. As a model organism I will employ planarians, flatworms with extraordinary plasticity that regenerate every piece of their body within a few days. I will mechanistically dissect how these animals rapidly induce an efficient regeneration program in response to tissue loss and define the key switches that determine whether a wound regenerates. Combining the astonishing regenerative abilities of planarians with new technologies I will first comprehensively describe the molecular changes occurring during the amputation response. Second, with a powerful novel assay developed in my lab - dormant fragments - that allows for the first time the separation of wounding from tissue loss in a single planarian, I will analyze the dynamics of the earliest regenerative events. Third, I will functionally characterize the regeneration-initiating signals and their target pathways combining in vivo RNAi and phenotypic assays. Fourth, with a regeneration-deficient planarian species, I will test whether the identified key regulators act as network nodes that can be utilized to rescue regeneration. Importantly, using vertebrate paradigms, such as the regenerating zebrafish fin, I will investigate conserved roles of these network nodes and validate general principles of regeneration initiation. This project will not only uncover conserved mechanisms of regeneration initiation but will also identify the switches that must be levered to induce regeneration in non-regenerating animals.

Mots-clés : tissue regeneration,animal models