Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : PREGBRAIN (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Pregnancy represents one of the most extreme endocrine events of life, involving unequaled hormone surges that orchestrate widespread maternal adaptations. Animal studies have demonstrated reproduction-related neural and behavioral changes that are evident across the lifespan. However, remarkably little is known on the effects of this monumental transition on the human brain. I have previously shown—for the first time—that pregnancy leads to long-lasting changes in human brain structure, revealing the existence of a dramatic pregnancy-related neuroplasticity in humans. Building on these results and new pilot data, I propose a cutting-edge research project that aims to A) comprehensively map the changes manifesting in a woman’s brain by tracking core aspects of brain anatomy and function across pregnancy and the postpartum period, B) pinpoint key factors driving pregnancy-related neuroplasticity by means of an extensive profile of endocrine and lifestyle changes, and C) reveal the neural substrates for potential adaptive and maladaptive processes, focusing on specific functional domains highlighted by promising pilot results. I postulate that pregnancy-related changes in a woman’s brain not only underlie well-known adverse peripartum processes such as the development of mental health disorders and memory issues, but also comprise adaptive processes conferring long-lasting changes in specific domains of functioning that play a key role in—but are not restricted to—maternal caregiving. I will investigate this novel topic by means of an innovative prospective cohort study tracking women from before conception across pregnancy and into the postpartum period, which combines cutting-edge neuroimaging approaches with various psychopedagogic and biomedical measures. The proposed project has the potential to lay a firm foundation for this emerging field of human neuroscience and generate groundbreaking insights into a woman’s remarkable neurobiological journey to motherhood.

Mots-clés : pregnancy,brain,motherhood
Projet ERC : IMMCEPTION (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Institut national de la santé et de la recherche médicale — Pays : France — Rôle : PI
Acronyme de l'entité : Inserm
Type d'entité : Recherche
Financement ERC de l'entité : 1497441.0 €

Preserving skin homeostasis depends on complex interactions among structural cells, immune cells, and the environment. Dysregulation of this delicate equilibrium contributes to the development of type 2 immunity-associated skin inflammation (i.e., allergic skin inflammation), including atopic dermatitis (AD). The skin is a complex organ harboring various tissue-resident immune cells (e.g., dendritic cells, mast cells and macrophages) and innervated by a meshwork of sensory nerves, including those involved in nociception (i.e., nociceptors), which respond to injurious or potentially damaging stimuli by transmitting signals to the spinal cord and brain. Despite their role in the transmission of sensation, recent evidences have suggested that nociceptors could be powerful regulators of ongoing immune response. We wish to use sophisticated mouse models and new in vivo imaging approaches to define the roles of subsets of dermal nociceptors, cationic neuropeptide substance P, dermal mast cells expressing the recently discovered receptor for cationic molecules Mas-related G protein-coupled receptor b2 (i.e., Mrgprb2), in a mouse model of AD that has many pathological, immunological, and gene expression similarities with the corresponding human disorder. We also will define the translational relevance of our mouse studies by performing parallel analyzes of nociceptors and mast cells in the lesional skin of patients from USA and France with clinically-established AD. To accomplish these goals, we have proposed herein a body of work that is solidly based on our preliminary data, with four Aims that will test innovative hypotheses by using informative genetic approaches, as well as new intravital imaging systems we recently developed. This work thus will address significant gaps in our knowledge about the pathophysiology of AD and has the potential to identify such neuro-immune interactions as a promising new therapeutic target in AD and perhaps other allergic disorders.

Mots-clés : allergic skin inflammation,mast cells,sensory neurons,skin barrier and intravital imaging
Projet ERC : Brain Health Toolbox (Horizon 2020, appel 2018, Starting 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 : 1498268.0 €

Preventing dementia and Alzheimer disease (AD) is a global priority. Previous single-intervention failures stress the critical need for a new multimodal preventive approach in these complex multifactorial conditions. The Brain Health Toolbox is designed to create a seamless continuum from accurate dementia prediction to effective prevention by i) developing the missing disease models and prediction tools for multimodal prevention; ii) testing them in actual multimodal prevention trials; and iii) bridging the gap between non-pharmacological and pharmacological approaches by designing a combined multimodal prevention trial based on a new European adaptive trial platform. Disease models and prediction tools will be multi-dimensional, i.e. a broad range of risk factors and biomarker types, including novel markers. An innovative machine learning method will be used for pattern identification and risk profiling to highlight most important contributors to an individual’s overall risk level. This is crucial for early identification of individuals with high dementia risk and/or high likelihood of specific brain pathologies, quantifying an individual’s prevention potential, and longitudinal risk and disease monitoring, also beyond trial duration. Three Toolbox test scenarios are considered: use for selecting target populations, assessing heterogeneity of intervention effects, and use as trial outcome. The project is based on a unique set-up aligning several new multimodal lifestyle trials aiming to adapt and test non-pharmacological interventions to different geographic, economic and cultural settings, with two reference libraries (observational - large datasets; and interventional - four recently completed pioneering multimodal lifestyle prevention trials). The Brain Health Toolbox covers the entire continuum from general populations to patients with preclinical/prodromal disease stages, and will provide tools for personalized decision-making for dementia prevention.

Mots-clés : dementia,alzheimer s disease,prediction,prevention,clinical trials,modifiable risk factors,biomarkers
Projet ERC : ADAPT (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : Tampere University — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2689147.0 €

Previous efforts to raise living standards have been based on relentlessly increasing combustion, causing environmental destruction at all scales. In addition to climate-warming CO2, fossil fuel combustion also produces a large number of organic compounds and particulate matter, which deteriorate air quality. The atmosphere is cleansed from such pollutants by gas-phase oxidation reactions, which are invariably mediated by peroxy radicals (RO2). Oxidation transforms initially volatile and water-insoluble hydrocarbons into water-soluble forms (ultimately CO2), enabling scavenging by liquid droplets. A minor but crucially important alternative oxidation pathway leads to oxidative molecular growth, and formation of atmospheric aerosols. Aerosols impart a huge influence on the atmosphere, from local air quality issues to global climate forcing, yet their formation mechanisms and structures of organic aerosol precursors remains elusive. In a paradigm change, RO2 was recently found to undergo autoxidation, enabling rapid aerosol precursor formation even at sub-second time-scales – in stark contrast to the long processing times (days - weeks) previously assumed to be necessary. We have shown how abundant biogenic hydrocarbons (BVOC) autoxidize, but due to key structural differences, the same pathways are not available for anthropogenic hydrocarbons (AVOC), and thus they were not expected to autoxidize. My preliminary experiments reveal that AVOCs do autoxidize, but the mechanism enabling this remain unknown. Crucially, the co-reactants shown to inhibit BVOC seem to enforce AVOC autoxidation – potentially explaining the recent mysterious discovery of new-particle formation in polluted megacities. In ADAPT, I will use a combination of novel mass spectrometric detection methods fortified by theoretical calculations, to solve the mechanism of AVOC autoxidation. This will directly assist both air quality management, and the design of cleaner fuels and engines.

Mots-clés : atmospheric pressure chemical ionization,atmospheric and combustion chemistry,gas phase organic oxidation reaction mechanisms,aerosol precursor formation,rapid free radical rearrangements
Projet ERC : HUMO (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Neuroscience and Disorders of the Nervous System
Entité participante : Sapienza University of Rome — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1028750.0 €

Primates live in a complex social environment, in which they need to maintain track of their past social interactions and learn to formulate prediction on what specific groupmates are likely to do based on their past experiences. I have previously contributed to show that the PF (prefrontal cortex) has a main function in the generation of goals based on the current contexts and events, but its role in social cognition is still little explored. In this context, the frontal Pole cortex (FPC) has been associated to “mentalizing” functions and there is a link between the autism spectrum disorder and its abnormalities. However until recently, no one has been able to record neural activity from FPC, but us. I propose to investigate the role of the monitoring function of FPC in association to the dorsolateral (PFD) and orbitofrontal (OFC) cortex, recording from the entire network up to 256 neurons simultaneously. We have developed the first human-monkeys (H-M) paradigm to test several hypotheses. The task is a non-match-to goal (NMTG) task in which the monkeys are trained to switch from their choice on the previous trial to a different one. In a subset of trials the monkey observe a human partner (either cooperative or uncooperative) performing the task. When the human partner conclude his turn, the monkeys have to switch to a new goal discarding the human’s previous goal. I will explore the role of PFD in social decisions in predicting other agents decisions and distinguishing and categorizing cooperative and uncooperative agents, and the role of OFC in monitoring others’ choices. I expect that PFD will maintain, as it does with past and future goals, separate records for the past choices of different agents while PFO might contribute to solve credit assignment problems also in relationship to other’s behaviors.

Mots-clés : monkeys,prefrontal cortex,frontal pole,goals
Projet ERC : Inflammostrome (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1599466.25 €

Pro-inflammatory cytokines play a crucial role in chronic inflammatory diseases. Focusing on spondyloarthritis (SpA), a prevalent and debilitating rheumatic condition characterized by inflammation and abnormal new bone formation, we demonstrated that TNF and IL-23/IL-17 inhibition potently blocks inflammation. However, these treatments have no proven effect on pathologic new bone formation and the resulting structural damage, indicating the unmet need for understanding upstream disease mechanisms. Immune cells, in particular myeloid cells, have been shown to be the major sources of TNF and IL-23 in experimental models. However, we and others failed to demonstrate abnormal cytokine production by myeloid cells in human SpA. What drives these pathogenic cytokines thus remains unknown. We recently found that SpA synovial tissues contain an abnormal stromal population of myofibroblasts, that these myofibroblasts express TNF and IL-23 in vivo and in vitro when exposed to cellular stress, and that stromal expression of these cytokines does not only drive inflammatory responses in vitro but is required and sufficient to induce experimental SpA in vivo. Therefore, we propose that stressed stromal cells can act as primary drivers of cytokine-mediated tissue inflammation and remodelling. Using a translational approach - dynamic sampling of primary human target tissues, functional experiments ex vivo and in vitro, animal models, and targeted interventions in patients – we aim to unravel the role of stromal cells in SpA by defining: 1) the molecular profile of the stromal alterations, 2) the mechanisms of cytokine production by stromal cells, 3) the activation of downstream inflammatory pathways, 4) the role of stromal alterations in tissue remodeling, and 5) the contribution of stromal pathways to experimental and human SpA. Collectively, this project will allow to validate stromal cells as novel therapeutic targets for SpA and related disorders.

Mots-clés : inflammatory diseases,anti cytokine therapy,disease remission,therapeutic targets
Projet ERC : COMPASS (Horizon 2020, appel 2016, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Earth system science
Entité participante : University of East Anglia — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : UEA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 3499269.98 €

Processes on the Antarctic continental shelf and slope are crucially important for determining the rate of future sea level rise, setting the properties and volume of dense bottom water exported globally, and regulating the carbon cycle. Yet our ability to model and predict these processes over future decades remains rudimentary. This deficiency in understanding originates in a lack of observations in this inaccessible region. The COMPASS project seeks to rectify that by exploiting new technology - autonomous marine vehicles called gliders - to observe, quantify and elucidate processes on the continental shelf and slope of Antarctica that are important for climate. The COMPASS objective is to make a step-change in our quantitative understanding of: (i) the ocean front that marks the boundary between the Antarctic continental shelf and the open ocean, and its associated current system; (ii) the interaction between ocean, atmosphere and sea-ice on the Antarctic continental shelf; and (iii) the exchange of heat, salt and freshwater with the cavities beneath ice shelves. These goals will be met by a series of targeted ocean glider campaigns around Antarctica, spanning different flow regimes, including areas where warm water is able to access the continental shelf and influence ice shelves, areas where the continental shelf is cold and fresh, and areas where the continental shelf hosts cold, salty, dense water that eventually spills into the abyss. A unique circumpolar assessment of ocean properties and dynamics, including instabilities and mixing, will be undertaken. COMPASS will develop new technology to deploy a profiling glider into inaccessible environments such as Antarctic polynyas (regions of open water surrounded by sea-ice). As well as scientific breakthroughs that will feed into future climate assessments, improving projections of future sea level rise and global temperatures, COMPASS will deliver enhanced design for future ocean observing systems.

Mots-clés : antarctica,marine autonomous vehicles
Projet ERC : PyroPop (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Cellular, Developmental and Regenerative Biology
Entité participante : Ghent University — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UGent
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 592586.21 €

Programmed cell death is essential for homeostasis, and its deregulation contributes to human disease. Inflammasome-induced pyroptosis of infected macrophages contributes to host defense against infections, but the concomitant release of inflammatory danger signals and leaderless cytokines is detrimental in chronic inflammatory diseases. The central hypothesis of the PyroPop ERC Consolidator project is that inflammasomes are cytosolic platforms that couple pathogen sensing to multiple programmed cell death modes. This is based on our preliminary data showing that inflammasomes can be triggered to switch from inflammatory pyroptosis to programmed necrosis and non-inflammatory apoptosis. This suggests that the (patho)physiological outcomes of inflammasome activation may be modulated for therapeutic purposes. However, the molecular machinery and effector mechanisms of pyroptosis, inflammasome-induced apoptosis and programmed necrosis are virtually unknown. My objectives are (i) to explore the cleavage events and subcellular dynamics of pyroptosis by proteomics and high-resolution time-lapse microscopy; (ii) to clarify the molecular mechanisms of pyroptosis and inflammasome-controlled cell death switching; and (iii) to address how inflammasome-associated cell death modes impact on anti-bacterial host defense and chronic inflammatory pathology in vivo through the identification of pyroptosis-selective biomarkers and clinical analysis of pyroptosis-deficient mouse models. The central hypothesis in this regard is that inflammasome-mediated secretion of leaderless cytokines (such as IL-1β and IL-18) and danger signals may be mechanistically coupled to pyroptosis, but not apoptosis induction. By clarifying the mechanisms of inflammasome-controlled programmed cell death, this project may set the path for the development of an entirely novel class of inflammation-modulating therapies that are based on converting inflammatory pyroptosis into non-inflammatory apoptosis.

Mots-clés : pyroptosis,apoptosis,inflammasome
Projet ERC : EQUIPTNT (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1398436.0 €

Progress in the fabrication, control and readout of systems consisting of a small number of qubits has catapulted quantum computation from a primarily theoretical pursuit into the lab. With the growing availability of small and relatively noise-free devices and the imminent arrival of larger next-generation equipment, new theoretical questions are being asked about the potential of quantum computation. In particular, one may ask if quantum computing devices may yield computational benefits even in the presence of noise or constraints on their size or geometrical layout of qubits. The project EQUIPTNT will characterize the computational capabilities of near-term quantum devices by studying their potential to yield disruptive boosts in information-processing power. It will investigate and design new quantum algorithms adapted to limited hardware: the aim here is to provide computational advances while maximizing noise-tolerance without placing excessive demands on experimental capabilities. It will establish trade-off relations between noise levels, computational power, and the amount and nature of available computational resources. EQUIPTNT will also develop tools for simulating the quantum many-body dynamics of information-processing setups by classical algorithms, in order to pinpoint the origin of quantum advantage, and provide means for certifying the functionality of quantum hardware. EQUIPTNT will establish new theoretical and algorithmic methods to address the question of ''best use'' for a given finite set of resources. Its interdisciplinary approach will yield novel principles for the design, simulation and validation quantum information processing protocols. Corresponding results will have direct application to near-term quantum devices, providing insights into the architecture and use of schemes tailored towards specific experimental platforms.
Projet ERC : Matryoshka (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Computer science and informatics
Entité participante : Institut national de recherche en sciences et technologies du numérique — Pays : France — Rôle : Partner
Acronyme de l'entité : Inria
Type d'entité : Recherche
Financement ERC de l'entité : 428750.0 €

Proof assistants are increasingly used to verify hardware and software and to formalize mathematics. However, despite the success stories, they remain very laborious to use. The situation has improved with the integration of first-order automatic theorem provers -- superposition provers and SMT (satisfiability modulo theories) solvers -- through middleware such as Sledgehammer for Isabelle, codeveloped by the PI; but this research has now reached the point of diminishing returns. Only so much can be done when viewing automatic provers as black boxes. To make interactive verification more cost-effective, we propose to deliver very high levels of automation to users of proof assistants by fusing and extending two lines of research: automatic and interactive theorem proving. This is our grand challenge. Our starting point is that first-order automatic provers are the best tools available for performing most of the logical work. Our approach will be to enrich superposition and SMT with higher-order reasoning in a careful manner, to preserve their desirable properties. We will design proof rules and strategies, guided by representative benchmarks from interactive verification. With higher-order superposition and higher-order SMT in place, we will develop highly automatic provers building on modern superposition provers and SMT solvers, following a novel stratified architecture. To reach end users, these new provers will be integrated in proof assistants, including Coq, Isabelle, and the TLA+ Proof System, and will be available as backends to more specialized verification tools. The users of proof assistants and similar tools stand to experience substantial productivity gains: In the past five years, the success rate of automatic provers on interactive proof obligations from a representative benchmark suite has risen from 47% to 77%; with this project, we aim at 90%--95% proof automation.

Mots-clés : automatic theorem proving,interactive theorem proving,proof assistants,smt solvers,superposition