Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : AUTISMS (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : University of Cyprus — Pays : Chypre — Rôle : Partner
Acronyme de l'entité : UCY
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 95224.15 €

Autism spectrum disorders (ASD) affect 1-2% of the population and are a major public health issue. Heterogeneity between affected ASD individuals is substantial both at clinical and etiological levels, thus warranting the idea that we should begin characterizing the ASD population as multiple kinds of ‘autisms’. Without an advanced understanding of how heterogeneity manifests in ASD, it is likely that we will not make pronounced progress towards translational research goals that can have real impact on patient’s lives. This research program is focused on decomposing heterogeneity in ASD at multiple levels of analysis. Using multiple ‘big data’ resources that are both ‘broad’ (large sample size) and ‘deep’ (multiple levels of analysis measured within each individual), I will examine how known variables such as sex, early language development, early social preferences, and early intervention treatment response may be important stratification variables that differentiate ASD subgroups at phenotypic, neural systems/circuits, and genomic levels of analysis. In addition to examining known stratification variables, this research program will engage in data-driven discovery via application of advanced unsupervised computational techniques that can highlight novel multivariate distinctions in the data that signal important ASD subgroups. These data-driven approaches may hold promise for discovering novel ASD subgroups at biological and phenotypic levels of analysis that may be valuable for prioritization in future work developing personalized assessment, monitoring, and treatment strategies for subsets of the ASD population. By enhancing the precision of our understanding about multiple subtypes of ASD this work will help accelerate progress towards the ideals of personalized medicine and help to reduce the burden of ASD on individuals, families, and society.

Mots-clés : autism,precision medicine,heterogeneity,subtypes,stratification,development,toddler,connectome,phenome,big data,brain,gene expression,fmri,clustering,biomarker
Projet ERC : KID (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : Italian Institute of Technology — Pays : Italie — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 148413.0 €

Autism spectrum disorders (ASDs) are a heterogeneous set of neurodevelopmental disorders characterized by deficits in social communication and reciprocal interactions, as well as stereotypic behaviours. Although early diagnosis followed by appropriate intervention appears to offer the best chance for significant health improvement and economic gain, diagnosis of autism remains complex and often difficult to obtain. Recent identification of atypical kinematic patterns in children and infants at increased risk for ASDs provides new insights into autism diagnostic and objective profiling. KiD intends to help move these insights into the development of a low cost, easy-to-use, yet reliable wearable tracking system, designed to assist detection and classification of ASDs. The novelty of KiD is to combine informed development of machine learning methods to classify kinematic data with a co-design human factor engineering. KiD holds great potential for translational possibilities into autism clinical practice. The main use of the device will be to assist clinicians to achieve expedited diagnosis, ensuring early and timely access of children at risk of autism to evidence-based intervention programs. Another use will be to examine the quantitative nature of autistic traits, enabling new forms of precision-phenotyping, which is potentially useful for stratifying patients with ASD and developing individualized treatment approaches.

Mots-clés : kinematic,autism,early diagnosis,clinical decision suport system,personalized phenotyping,machine learning,human factor engineering
Projet ERC : Autophagy in vitro (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Institut Pasteur — Pays : France — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1185057.5 €

Autophagy is a catabolic pathway that delivers cytoplasmic material to lysosomes for degradation. Under vegetative conditions, the pathway serves as quality control system, specifically targeting damaged or superfluous organelles and protein-aggregates. Cytotoxic stresses and starvation, however, induces the formation of larger autophagosomes that capture cargo unselectively. Autophagosomes are being generated from a cup-shaped precursor membrane, the isolation membrane, which expands to engulf cytoplasmic components. Sealing of this structure gives rise to the double-membrane surrounded autophagosomes. Two interconnected ubiquitin (Ub)-like conjugation systems coordinate the expansion of autophagosomes by conjugating the autophagy related (Atg)-protein Atg8 to the isolation membrane. In an effort to unravel the function of Atg8, we reconstituted the system on model membranes in vitro and found that Atg8 forms together with the Atg12–Atg5-Atg16 complex a membrane scaffold which is required for productive autophagy in yeast. Humans possess seven Atg8-homologs and two mutually exclusive Atg16-variants. Here, we propose to investigate the function of the human Ub-like conjugation system using a fully reconstituted in vitro system. The spatiotemporal organization of recombinant fluorescent-labeled proteins with synthetic model membranes will be investigated using confocal and TIRF-microscopy. Structural information will be obtained by atomic force and electron microscopy. Mechanistic insights, obtained from the in vitro work, will be tested in vivo in cultured human cells. We belief that revealing 1) the function of the human Ub-like conjugation system in autophagy, 2) the functional differences of Atg8-homologs and the two Atg16-variants Atg16L1 and TECPR1 and 3) how Atg16L1 coordinates non-canonical autophagy will provide essential insights into the pathophysiology of cancer, neurodegenerative, and autoimmune diseases.

Mots-clés : autophagy,in vitro reconstitution,model membranes
Projet ERC : LIP-ATG (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
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 : 1499880.0 €

Autophagy is an intracellular catabolic process critical to eukaryotic life and indispensable for plant survival to drought, nutrient scarcity or pathogen attacks. Autophagy relies on the formation of specialized vesicles called autophagosomes (AP) which engulf and deliver cell components to the lytic vacuole. AP biogenesis is carried out by a group of dedicated proteins (named ATG) and hinges on intense remodelling events and on the remarkable capacity of an initial membrane, the phagophore, to assemble de novo, shape like a cup, expand while maintaining structure and function and re-shape to a complete vesicle. To date the molecular mechanisms underlying these events remain elusive. Research has focused on the role of autophagy proteins but, despite AP biogenesis being a membrane-based process, the fundamental contributions of lipids to AP membrane formation, identity and activities have been largely unexplored; in other words, when it comes to AP formation we are only looking at half of the picture. I propose to address the fundamental question of how APs form and shape from a novel angle: by exploring how lipids’ nature, dynamics and lateral heterogeneity instruct the phagophore structure, its protein composition and its functions. The project builds on our recent results and expands on strategies that we have developed, integrating proteomic/bioinformatic approaches, lipidomics and high-resolution 3D imaging. We will tackle 3 complementary objectives: 1) Reveal the dynamic lipid signature of the phagophore, 2) Elucidate the implication of lipids nature and repartition in the phagophore ultrastructure, 3) Decrypt the molecular mechanisms by which lipids interplay with ATG proteins to control autophagy activity and plant physiology. Overall the project will articulate an integrated vision of the molecular processes controlling autophagy and provide fundamental knowledge in our understanding of plant adaptive programs.

Mots-clés : plant biology,plant adaptive responses
Projet ERC : PREG-LAB (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
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 : 1919811.06 €

B cells can act both as negative regulators and as drivers of immunity through the production of cytokines. Through secretion of interleukin (IL)-10 B cells inhibited immunity in autoimmune and infectious diseases. For instance, IL-10 from B cells drove complete recovery from disease in experimental autoimmune encephalomyelitis (EAE), the primary animal model for multiple sclerosis (MS), while a lack of IL-10 production by B cells resulted in a severe chronic EAE. B cells can also suppress immunity via IL-35. Human B cells might similarly play inhibitory roles. In few patients with immune-mediated diseases B cell depletion therapy with Rituximab was associated with exacerbation of symptoms, or onset of new pathologies. Conversely, an opposite role of B cells as drivers of immunity was highlighted by the beneficial effect of Rituximab in some patients with rheumatoid arthritis or MS. Clinical improvement often precedes reduction in autoantibody levels in Rituximab treated patients, indicating that B cell-mediated pathogenesis is largely antibody-independent. A candidate factor for the deleterious effects of B cells in MS is IL-6. IL-6 secretion is a major mechanism of B cell-mediated pathogenesis in EAE, and B cells from MS patients produced more IL-6 than cells from healthy individuals. There is now an urgent need for the characterization of the phenotypes of the B cells producing IL-6, IL-10, and IL-35 in vivo at single cell and molecular levels. Markers for these cells might allow understanding the paradoxical effects of B cell-depletion therapy, and guide the development of novel agents depleting distinctively pro-inflammatory B cells, while sparing the remaining of the B cell compartment. Using advanced genetic models to identify and track cytokine-expressing cells, our project aims at characterizing B cells with pro- and anti-inflammatory functions in mice in vivo, to subsequently guide the identification of comparable markers in human.

Mots-clés : b cell,il 10,il 35,plasma cell,autoimmunity
Projet ERC : HeartGenes (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Eastern Finland — Pays : Finlande — Rôle : PI
Acronyme de l'entité : UEF
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2500000.0 €

BACKGROUND: Therapeutic angiogenesis has great potential for the treatment of severe heart diseases. However, this requires novel approaches and development of new technology. ADVANCING STATE-OF-THE-ART: We will develop novel VEGF-B and VEGF-C-based gene therapy to treat refractory angina and heart failure (HF). VEGF-B and VEGF-C lead factors were selected from extensive pig studies where they showed the best benefits among all VEGFs, such as relative cardiac specificity, potent angiogenic and metabolic effects (VEGF-B) and lymphangiogenic activity (VEGF-C). Exogenous gene transfer and new endogenous gene activation technology will be developed. Key new technologies are riboswitch-regulated-AAV8 vectors, Super-Enhancer driven cell-type targeted gene expression, VEGF-B and VEGF-C designer mutants for better efficacy and activation of natural endogenous VEGF-B and VEGF-C expression with promoter binding shRNAs, circRNAs, CRISPR/mutantCas9-VP64-SAM gene activation technology and using a novel concept of the release of promoter pausing. Immunological concerns of AAV8 and usefulness of new synthetic dendrimer carriers will be addressed. HeartGenes utilizes optimized percutaneous intramyocardial and retrograde venous gene delivery in pig chronic ischemia and HF models, clinically relevant pig exercise test, and 15O-H2O and 18F-FDG PET/MRI imaging to detect treatment effects. Simultaneously, HeartGenes will take a realistic approach to clinical translation and starts intramyocardial vs retrograde venous riboswitch-AAV8-VEGF-B186 phase I trial in refractory angina as the first step to bring the best novel constructs and the most advanced functional and imaging endpoints developed in HeartGenes to clinical testing at the end of the project. SIGNIFICANCE: If successful, this approach will bring a paradigm shift to cardiac gene therapy and new therapeutic options for heart diseases. Novel new technologies may also become widely applicable in other areas of medicine.

Mots-clés : angiogenesis,cardiovascular diseases,clinical trial,endogenous gene regulation,gene therapy,imaging,ischemia,non coding rnas,promoter pausing,translational studies,vascular endothelial growth factors,vectors
Projet ERC : BEHAVFRICTIONS (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of Zurich — Pays : Suisse — Rôle : Partner
Acronyme de l'entité : UZH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 450185.0 €

BEHAVFRICTIONS will use novel models focussing on information-processing frictions to explain choice patterns described in behavioral economics and psychology. The proposed research will provide microfoundations that are essential for (i) identification of stable preferences, (ii) counterfactual predictions, and (iii) normative conclusions. (i) Agents who face information-processing costs must trade the precision of choice against information costs. Their behavior thus reflects both their stable preferences and the context-dependent procedures that manage their errors stemming from imperfect information processing. In the absence of micro-founded models, the two drivers of the behavior are difficult to disentangle for outside observers. In some pillars of the proposal, the agents follow choice rules that closely resemble logit rules used in structural estimation. This will allow me to reinterpret the structural estimation fits to choice data and to make a distinction between the stable preferences and frictions. (ii) Such a distinction is important in counterfactual policy analysis because the second-best decision procedures that manage the errors in choice are affected by the analysed policy. Incorporation of the information-processing frictions into existing empirical methods will improve our ability to predict effects of the policies. (iii) My preliminary results suggest that when an agent is prone to committing errors, biases--such as overconfidence, confirmatory bias, or perception biases known from prospect theory--arise under second-best strategies. By providing the link between the agent's environment and the second-best distribution of the perception errors, my models will delineate environments in which these biases shield the agents from the most costly mistakes from environments in which the biases turn into maladaptations. The distinction will inform the normative debate on debiasing.

Mots-clés : stochastic choice,information processing frictions,error management,microfoundations of behavioural economics
Projet ERC : BeyondOpposition (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : National University of Ireland — Pays : Irlande — Rôle : Partner
Acronyme de l'entité : NUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 0.0 €

BEYONDOPPOSITION will be the first large-scale, transnational study to consider the effects of recent Sexual and Gender Rights and Equalities (SGRE) on those who oppose them, by exploring opponents’ experiences of the transformation of everyday spaces. It will work beyond contemporary polarisations, creating new possibilities for social transformation. This cutting-edge research engages with the dramatically altered social and political landscapes in the late 20th and early 21st Century created through the development of lesbian, gay, bisexual, and trans, and women’s rights. Recent reactionary politics highlight the pressing need to understand the position of those who experience these new social orders as a loss. The backlash to SGRE has coalesced into various resistances that are tangibly different to the classic vilification of homosexuality, or those that are anti-woman. Some who oppose SGRE have found themselves the subject of public critique; in the workplace, their jobs threatened, while at home, engagements with schools can cause family conflicts. This is particularly visible in the case studies of Ireland, UK and Canada because of SGRE. A largescale transnational systematic database will be created using low risk (media and organisational discourses; participant observation at oppositional events) and higher risk (online data collection and interviews) methods. Experimenting with social transformation, OPPSEXRIGHTS will work to build bridges between ‘enemies’, including families and communities, through innovative discussion and arts-based workshops. This ambitious project has the potential to create tangible solutions that tackle contemporary societal issues, which are founded in polarisations that are seemingly insurmountable.

Mots-clés : social geography,social justice,lesbian,bisexual,trans,reproductive rights,queer
Projet ERC : BeyondOpposition (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Institutions, Governance and Legal Systems
Entité participante : National University of Ireland — Pays : Irlande — Rôle : PI
Acronyme de l'entité : NUI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1640961.0 €

BEYONDOPPOSITION will be the first large-scale, transnational study to consider the effects of recent Sexual and Gender Rights and Equalities (SGRE) on those who oppose them, by exploring opponents’ experiences of the transformation of everyday spaces. It will work beyond contemporary polarisations, creating new possibilities for social transformation. This cutting-edge research engages with the dramatically altered social and political landscapes in the late 20th and early 21st Century created through the development of lesbian, gay, bisexual, and trans, and women’s rights. Recent reactionary politics highlight the pressing need to understand the position of those who experience these new social orders as a loss. The backlash to SGRE has coalesced into various resistances that are tangibly different to the classic vilification of homosexuality, or those that are anti-woman. Some who oppose SGRE have found themselves the subject of public critique; in the workplace, their jobs threatened, while at home, engagements with schools can cause family conflicts. This is particularly visible in the case studies of Ireland, UK and Canada because of SGRE. A largescale transnational systematic database will be created using low risk (media and organisational discourses; participant observation at oppositional events) and higher risk (online data collection and interviews) methods. Experimenting with social transformation, OPPSEXRIGHTS will work to build bridges between ‘enemies’, including families and communities, through innovative discussion and arts-based workshops. This ambitious project has the potential to create tangible solutions that tackle contemporary societal issues, which are founded in polarisations that are seemingly insurmountable.

Mots-clés : social geography,social justice,lesbian,bisexual,trans,reproductive rights,queer
Projet ERC : SELECTIONDRIVEN (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Copenhagen — Pays : Danemark — Rôle : PI
Acronyme de l'entité : UCPH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499600.0 €

Background Lethal epidemics like the Black Death have killed millions of people and must pose an extreme selective pressure on any genetic variant that confers disease protection. Therefore, such epidemics have been hypothesized to play a key role in the evolution of humans. To what extent this is true, is a fundamental question of wide interest. Yet, it remains unanswered, in part due to limitations of the current methods to detect signatures of selection. Objectives I wish to accomplish three linked goals with the proposed project. The first goal is to develop new statistical methods for detecting signatures of adaptive natural selection driven by lethal epidemics. The second goal is to use these new methods to investigate the role of epidemics in recent human evolution by applying them to genetic data from several recent epidemics. The third goal is to gain insights into mechanisms that protect against infectious disease via the identification of genetic variants that have been under selection because they confer disease protection. Methods To reach these goals, extensive simulations will be performed to carefully characterize the genetic signatures of adaptive selection acting on a protective genetic variant during an epidemic. Then new statistical methods that can detect these signatures will be developed. Next, the new methods will be applied to several real datasets, including one from a recent Ebola epidemic. Finally, all signatures of selection detected in these real datasets will be further investigated. Expected outcome and importance This project will deliver new statistical methods that will move the field of selection studies a substantial step beyond the state-of-the-art by filling an important methodological gap. It will also yield key insights into the role of epidemics in recent evolutionary history. Finally, it has the potential to provide new knowledge on the genetics of disease resistance that could help prevent future lethal epidemics.

Mots-clés : natural selection,epidemics,recent human evolution