Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ANIMATE (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Freiburg — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499946.0 €

Atherosclerosis is a chronic immune disease of arteries that causes vessel-narrowing atherosclerotic plaques. Its acute complications, myocardial infarction and stroke, are the leading causes of death worldwide. Atherosclerosis is accompanied by an inflammatory and autoimmune response with CD4+ T-helper cells that recognize self-antigens, including ApoB-100 (ApoB), the main protein in low-density lipoprotein (LDL) cholesterol. Although their existence has been inferred from indirect evidence, the existence and function of atherosclerosis-specific, self-reactive CD4+ T cells on a single-cell level remains elusive. In particular, it is unclear whether these are pro- or anti-inflammatory. Preliminary data suggest the existence of a natural pool of ApoB-reactive T-helper cells that share properties with atheroprotective T-regulatory cells but transform into pathogenic T-effector cells in the natural course of disease. This proposal aims to explore this loss of protective immunity on a cellular and function level. It employs novel tools to detect antigen-specific T cells in vivo by MHC-II multimers, mass cytometry (CyTOF), single cell RNA-sequencing (scRNA-seq), lineage-tracing mouse models, and live cell imaging. Based on the anticipated findings, this study will define a map of auto-reactive T-helper cell phenotypes in a temporal, spatial, and functional dimension. These insights will be used to identify novel immunomodulatory strategies to therapeutically stabilize the population of protective ApoB-specific T-helper cells, or to prevent their transformation into pathogenic T cell phenotypes by adoptive cells transfers, vaccination, or cytokine-blockade. In clinical association studies, a direct correlation of auto-immunity and clinical atherosclerosis will be tested. This proposal will decipher traits of protective immunity in atherosclerosis and help to build the conceptual framework to define novel therapeutic strategies for patients.

Mots-clés : atherosclerosis,inflammation,adaptive immunity,apob,t cells,vaccination,immunomodulation
Projet ERC : EXPLOSIA (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Ministry of Health — Pays : Espagne — Rôle : Partner
Type d'entité : Recherche
Financement ERC de l'entité : 702755.0 €

Atherosclerosis is considered an inflammatory disease caused by the accumulation, modification and immune cell recognition of low-density lipoproteins in the arterial wall. Plaque macrophages are held to be the main drivers of disease activity, whereas smooth muscle cells (SMCs) have traditionally been considered protective by forming fibrous tissue that stabilises plaques from undergoing rupture and causing thrombosis. In the present project, we challenge this dichotomous view of cellular villains and heroes in atherosclerosis. Using lineage tracking techniques in mice, we and others have uncovered a large population of SMCs in plaques, which has escaped detection because the cells completely lose conventional SMC phenotype. Strikingly, we have found that the entire plaque SMC population derives from only few founder SMCs that undergo massive clonal expansion and phenotypic modulation during lesion formation. We hypothesise that the balance between the different modulated SMC subtypes and the functions they carry are central to lesion progression. In EXPLOSIA we will address this hypothesis in 3 steps. First, we will conduct a comparative analysis of clonal structure in mice, minipigs, and humans. Second, we will determine links between SMC subtypes, their gene expression programs, and atherosclerotic disease activity by combining single-cell transcriptomics with novel techniques to alter atherosclerotic disease activity in gene-modified mice and minipigs. Third, we will develop techniques for manipulating genes in modulated plaque SMCs and test the causal role of perturbing SMC subtypes and function for lesion progression. The aim of the project is to answer the following key questions for a deeper understanding of atherosclerosis: - What is the clonal architecture of SMCs in human atherosclerosis? - What is the SMC gene expression signature of atherosclerotic disease activity? - Can interventions targeting SMCs prevent dangerous lesion development?

Mots-clés : atherosclerosis,smooth muscle cells,experimental animal models
Projet ERC : EXPLOSIA (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Aarhus University — Pays : Danemark — Rôle : PI
Acronyme de l'entité : AU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1296120.0 €

Atherosclerosis is considered an inflammatory disease caused by the accumulation, modification and immune cell recognition of low-density lipoproteins in the arterial wall. Plaque macrophages are held to be the main drivers of disease activity, whereas smooth muscle cells (SMCs) have traditionally been considered protective by forming fibrous tissue that stabilises plaques from undergoing rupture and causing thrombosis. In the present project, we challenge this dichotomous view of cellular villains and heroes in atherosclerosis. Using lineage tracking techniques in mice, we and others have uncovered a large population of SMCs in plaques, which has escaped detection because the cells completely lose conventional SMC phenotype. Strikingly, we have found that the entire plaque SMC population derives from only few founder SMCs that undergo massive clonal expansion and phenotypic modulation during lesion formation. We hypothesise that the balance between the different modulated SMC subtypes and the functions they carry are central to lesion progression. In EXPLOSIA we will address this hypothesis in 3 steps. First, we will conduct a comparative analysis of clonal structure in mice, minipigs, and humans. Second, we will determine links between SMC subtypes, their gene expression programs, and atherosclerotic disease activity by combining single-cell transcriptomics with novel techniques to alter atherosclerotic disease activity in gene-modified mice and minipigs. Third, we will develop techniques for manipulating genes in modulated plaque SMCs and test the causal role of perturbing SMC subtypes and function for lesion progression. The aim of the project is to answer the following key questions for a deeper understanding of atherosclerosis: - What is the clonal architecture of SMCs in human atherosclerosis? - What is the SMC gene expression signature of atherosclerotic disease activity? - Can interventions targeting SMCs prevent dangerous lesion development?

Mots-clés : atherosclerosis,smooth muscle cells,experimental animal models
Projet ERC : GUTSY (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Uppsala University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Atherosclerosis is the main pathological mechanism causing myocardial infarction and ischemic stroke. Evidence has mounted about the association between the gut microbiota and cardiovascular disease, but whether the associations are causal is largely unknown. For optimal prevention and treatment of cardiovascular disease, there is an urgent need to determine whether there are any true effects that might be targeted by interventions. The overall goal of this project is to assess causality between gut microbiota and atherosclerotic disease and to provide easily accessible biomarkers for an atherosclerosis-enhancing gut microbiota. To this end, the research program has three main objectives: 1.) Identification of gut microbiota characteristics associated with atherosclerosis measured by coronary computed tomography angiography and high-resolution carotid ultrasound in a population-based sample of 10,000 individuals and through prospective follow-up for myocardial infarction and ischemic stroke. The microbiota will be characterized by next-generation sequencing techniques in faecal samples. 2.) Identification of plasma biomarkers associated with an atherosclerosis- enhancing microbiota using comprehensive metabolomics profiling of 800 named metabolites in plasma from 800 individuals with replication in additional 800 individuals 3.) Clarification of the causal effects of gut microbiota characteristics on atherosclerosis, myocardial infarction and stroke by development of novel genetic instruments and applying Mendelian Randomization analysis I have access to unique study materials and documented experience of successful projects using large scale -omics data and state-of-the-art epidemiological methodologies. My project is expected to lead to the identification of characteristics of an atherosclerosis-enhancing gut microbiota and associated plasma biomarkers that may open up new avenues for effective prevention of atherosclerotic disease.

Mots-clés : atherosclerosis,mendelian randomization,microbiome
Projet ERC : CD40-INN (Horizon 2020, appel 2015, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1599536.25 €

Atherosclerosis, the underlying cause of the majority of cardiovascular diseases (CVD), is a lipid driven, inflammatory disease of the large arteries. Despite a 25% relative risk reduction achieved by lipid-lowering treatment, the vast majority of atherosclerosis-induced CVD risk remains unaddressed. Therefore, characterizing mediators of the inflammatory aspect of atherosclerosis is a widely recognized scientific goal with great therapeutic implications. Co-stimulatory molecules are key players in modulating immune interactions. My laboratory has defined the co-stimulatory CD40-CD40L dyad as a major driver of atherosclerosis. Inhibition of CD40, and of its interaction with the adaptor molecule TRAF6 by genetic deficiency, antibody treatment or (nanoparticle based) small molecule inhibitor (SMI) treatment, is one of the most powerful therapies to reduce atherosclerosis in a laboratory setting. Although CD40-CD40L interactions are associated with adaptive immunity, I recently identified the macrophage as a driver of CD40-induced inflammation in atherosclerosis. We will use state-of-the-art in vitro experiments, live cell-, super resolution imaging, proteomics approaches and mutant mouse models to unravel the role of macrophage CD40 in atherosclerosis. Moreover, using structure based virtual ligand screening, I will develop lead SMIs targeting macrophage CD40-signaling, which I will deliver using macrophage-targeting nanoparticles. My goal is to define the role of macrophage CD40 in inflammation and immunity and disentangle how its activation affects atherosclerosis. I will finally test the feasibility of targeting macrophage CD40-signaling as a treatment for CVD. These studies will define the role of CD40-signaling in the innate immune system in health and (cardiovascular) disease. As components of macrophage CD40-signaling have the potential to be amenable to pharmacological manipulation, we will establish their feasibility as novel targets for (CVD) treatment.

Mots-clés : atherosclerosis,inflammation,immunology
Projet ERC : ISCQuM (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Condensed matter physics
Entité participante : Board of the Swiss Federal Institutes of Technology — Pays : Suisse — Rôle : PI
Acronyme de l'entité : ETH Zurich
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1994385.0 €

Atomic confinement in 2D materials, topological protection in strong spin-orbit coupling systems or chiral magnets, all result in spin/charge textured states of matter. For example skyrmions, a whirling distribution of spins, behave as individual particles which controlled creation/annihilation/motion is of great importance in spintronics. To achieve control over skyrmions, or more generally over the constituents of disordered elastic media (vortices in superconductors, domain walls in magnets to name a few), the fundamental interplay between short-range and long-range interactions, influenced by topological protection, disorder and confinement, has to be understood and manipulated. This project aims at controlling with electromagnetic pulses a handful of charges and spins in nanostructured materials to be filmed with nm/fs resolution by time-resolved Transmission Electron Microscopy. I propose to image and shape confined electromagnetic fields (plasmons) in nanostructured novel materials. With this ability, we will implement/demonstrate the ultrafast writing and erasing of individual skyrmions in topological magnets. These experiments will enable the fundamental investigation of defects in topological networks and possibly seed new ideas for application in ultradense and ultrafast data storage devices. Similarly, pinning of vortices in type II superconductors will be controlled by light and imaged, gaining new insights into out of equilibrium superconductivity. In my laboratory, shaping and filming plasmonic fields down to the nm-fs scales have been demonstrated, as well as laser-writing and imaging skyrmions in nanostructures. ISCQuM will allow implementing crucial advances: i) extending our photoexcitation to the far-infrared for creating few-cycles electromagnetic pulses and exciting structural or electronic collective modes; ii) upgrading our detection to higher sensitivity and spatial resolution, extending our ability to image spin and charge distributions.

Mots-clés : ultrafast transmission electron microscopy,out of equilibrium,electron spectroscopy,skyrmions,lorentz microscopy,plasma resonances
Projet ERC : HDEM (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Antwerp — Pays : Belgique — Rôle : PI
Acronyme de l'entité : UAntwerp
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1130164.69 €

Atomic resolution microscopy relies on beams of energetic electrons. These beams quickly destroy fragile materials, making imaging them a major challenge. I have recently developed a new approach that provides the greatest possible resolving power per electron. The method provides both double resolution and excellent noise rejection, via multidimensional data acquisition and analysis. Here I propose to couple the new method with breakthroughs in high speed cameras to achieve unprecedented clarity at low doses, almost guaranteeing major advances for imaging beam sensitive materials. Proof of principle will be achieved for biochemical imaging using the easy to handle, commercially available GroEL chaperone molecule. We will combine our enhanced imaging capabilities with the averaging methods recently recognized by the Nobel prize in chemistry for imaging biomolecules at ultra low doses. After proving our low dose capabilities we will apply them to imaging proteins of current interest at greater resolution. Similar techniques will be used for fragile materials science samples, for instance metal organic framework, Li ion battery, 2D, catalyst and perovskite solar cell materials. Furthermore the same reconstruction algorithms can be applied to simultaneously acquired spectroscopic images, allowing us to not only locate all the atoms, but identify them. The properties of all materials are determined by the arrangement and identity of their atoms, and therefore our work will impact all major areas of science, from biology to chemistry and physics.

Mots-clés : atomic resolution scanning transmission electron microscopy,electron ptychography,single particle analysis,phase contrast imaging,adf imaging,elemental mapping,low dose imaging
Projet ERC : AtoFun (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Oxford — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1610231.0 €

Atomic scale defects play a key role in determining the behaviour of all crystalline materials, profoundly modifying mechanical, thermal and electrical properties. Many current technological applications make do with phenomenological descriptions of these effects; yet myriad intriguing questions about the fundamental link between defect structure and material function remain. Transmission electron microscopy revolutionised the study of atomic scale defects by enabling their direct imaging. The novel coherent X-ray diffraction techniques developed in this project promise a similar advancement, making it possible to probe the strain fields that govern defect interactions in 3D with high spatial resolution (<10 nm). They will allow us to clarify the effect of impurities and retained gas on dislocation strain fields, shedding light on opportunities to engineer dislocation properties. The exceptional strain sensitivity of coherent diffraction will enable us to explore the fundamental mechanisms governing the behaviour of ion-implantation-induced point defects that are invisible to TEM. While we concentrate on dislocations and point defects, the new techniques will apply to all crystalline materials where defects are important. Our characterisation of defect structure will be combined with laser transient grating measurements of thermal transport changes due to specific defect populations. This unique multifaceted perspective of defect behaviour will transform our ability to devise modelling approaches linking defect structure to material function. Our proof-of-concept results highlight the feasibility of this ambitious research project. It opens up a vast range of exciting possibilities to gain a deep, fundamental understanding of atomic scale defects and their effect on material function. This is an essential prerequisite for exploiting and engineering defects to enhance material properties.

Mots-clés : coherent x ray diffraction,dislocations,atomic scale point defects,ion implantation,thermal transport,lattice strain
Projet ERC : FESTA (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : National Research Council — Pays : Italie — Rôle : PI
Acronyme de l'entité : CNR
Type d'entité : Recherche
Financement ERC de l'entité : 150000.0 €

Attosecond science studies the motion of electrons on atomic and molecular scale, which typically occurs on the timescale of attoseconds (1 as = 10^-18 s). This motion is at the basis of all fundamental processes occurring in Chemistry, Material Science and Biology, and its understanding enables innovation in all these scientific fields. The access to electronic motion on the timescale of attoseconds is based on the analysis of extreme ultra-violet (EUV) harmonic radiation generated when a molecule is hit by an intense femtosecond (1 fs = 10^-15 s) laser pulse. However, despite its huge potential, the full exploitation of this approach is currently hindered by limitations in the commercially available EUV spectrometers and it is restricted to a few very specialized users who are able to build their own instruments. By exploiting the innovative technical methods developed during UDynI ERC, we want to realize a compact, versatile, and user-friendly EUV spectrometer, which overcomes these limitations. In this way, we will grant access to attosecond science to a wider range of stakeholders in fields with high impact on the society, such as Health (e.g. drug discovery), Environment (e.g. understanding atmospheric photoinduced pollution, finding more effective chemical and catalytic processes) and Technology (e.g. study of high temperature superconductors and ultrafast switching in magnetic materials). The objective of the FESTA PoC Project is the development of a EUV detection system prototype (TRL6), the identification of a proper IPR exploitation strategy and the definition of the most suitable business model for the commercialization of the FESTA platform.

Mots-clés : high order harmonic generation,attosecond spectroscopy
Projet ERC : THERAUTISM (Horizon 2020, appel 2019, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
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 : 1499025.0 €

Autism is the major neurodevelopmental health public issue, affecting 1/100 child births worldwide. These disorders are diagnosed before the age of 3, based on behavioural cues: deficits in social interaction and communication as well as stereotyped and restrained behaviours. There is no medication to improve this condition. Most recent molecular targets identified within narrow frameworks (unspecific molecule, single tissue targeted, single disease model used) have failed in clinical trials. My first objective aims at thwarting this autism research gap, unravelling the common molecular and cellular dysfunctions underlying autism-related behaviours across several preclinical models and neuronal circuits. In particular, setting up translatomic analyses in these paradigms will identify and validate new molecular therapeutic targets. I recently deciphered one such molecular substrate, involving the loss of oxytocin transcripts in oxytocinergic axon terminals thus demonstrating the feasibility of this global approach. The second major objective of my project is to hijack the properties of a newly identified protein function to restore this new target and rescue social deficits in different preclinical models of autism. This would yield a novel and safe gene therapy vector which has never been explored before. Altogether, my research project will deliver strategic resources to the scientific and medical communities that will spur the development of new treatment options for autistic patients.

Mots-clés : autism,translatome,oxytocin