Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : ImpulsiveFlows (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Delft University of Technology — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : TU Delft
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499567.5 €

My goal is to investigate impulsive flows that occur both in nature and technological applications, where fluid is accelerated due to sudden motion of an object or boundary, which leads to an additional instationary drag or lift forces. This project will shed new light on the understanding of the fundamental properties and flow physics of these impulsive flows. Theoretical concepts that are used today, do not go much beyond those laid down almost 100 years ago. With today’s level of technology and experimental tools I will be able to break new ground in the understanding of these flow phenomena that are very challenging both experimentally and numerically. First, a novel-concept flow facility will be built, based on a high performance robotic arm; this robot arm can move and rotate various objects in a water-filled tank along prescribed trajectories with known acceleration and rotation. The fluid motion is measured using tomographic particle image velocimetry (PIV), of which the measurement volume can move along with the objects using auxiliary robot arms. New PIV approaches will be developed that measure fluid acceleration varied within the short times of these impulsive motions. Then a systematic investigation is performed on various impulsive flows where the rate of acceleration and rotation rate can be varied, in order to find new and improved relationships between the measured hydrodynamic force histories and relevant flow quantities, such as velocity, acceleration, and rotation rate, and the time scales at which these phenomena occur. These will represent real-life impulsive flows. Experimental approaches and results will be used to validate numerical methods. The results of this investigation will fill gaps in our knowledge of impulsive flows, and give more accurate estimates of hydrodynamic forces. This will improve the prediction of structural loads and reduce failure and discomfort, with impact on aeronautics, wind energy, maritime and offshore technology.

Mots-clés : experimental fluid mechanics,unsteady hydrodynamic forces,fluid structure interaction
Projet ERC : EVOMORPHYS (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : University of Geneva — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UNIGE
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2499070.0 €

My project focuses on answering one fundamental question: what are the drivers of Life’s morphological complexity and diversity? I claim that this question can only be addressed by a Newtonian-Darwinian synthesis that considers how Evolution exploits the physical properties of living matter. I will investigate how the evolutionary process explores the phase space of possible interactions between physical (mechanics, reaction-diffusion) and biological (cell signalling, proliferation, migration) processes and generates configurations that compute functional phenotypes. In particular, I will combine experiments in biology and physics, as well as mathematical models and Artificial-Life (ALife) numerical simulations. The latter will be based on physics’ first principles, symmetry-breaking processes and a genetic algorithm. First, I will investigate how geometry affects signalling by (i) imaging the embryonic development of colour patterns and skin geometries of multiple squamate species with various scale-to-colour pattern correspondences, (ii) generating CRISPR/Cas9 scaleless mutants in two lizard species to study the effect of skin 3D geometry on colour patterning, and (iii) performing ALife experiments to explore how the evolutionary process can modify signalling events and exploit geometry to generate new patterns. Second, I will analyse how growth can affect geometry by (i) performing in-silico experiments where coupling between growth and morphogenesis is systematically explored and (ii) evaluating how much the in-silico model captures morphologies generated with physics laboratory experiments using 3D layered polymeric gels. Third, I will build a Newtonian-Darwinian framework by coupling geometry, signalling, growth and mechanics in extensive open-ended ALife experiments. The results of the EVOMORPHYS project will constitute a novel framework for understanding how Evolution exploits physics to generate the morphological diversity and complexity of Life forms.

Mots-clés : evolution,artificial life,numerical simulations
Projet ERC : MULTISCALE (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Amsterdam — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UvA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

My project will boost the precision of theoretical predictions for collisions at the Large Hadron Collider. Precise predictions are crucial to further constrain the properties of the recently-discovered Higgs boson, and uncover a faint signal of Beyond-the-Standard Model physics. I will focus on the strong interactions, which dominate the theoretical uncertainty and play a role at multiple energy scales, including those related to the incoming protons, the hard scattering, the masses of (new) particles, the transverse momentum and size of jets. The critical progress of this proposal lies in taking this intrinsically multi-scale nature into account, moving beyond the current trade-off between precision and realism in the three dominant calculational paradigms. Fixed-order calculations are systematically improvable but assume that there is no hierarchy between perturbative scales. Monte Carlo event generators provide a fully exclusive description of the final state, but are currently limited to leading-logarithmic order and lack theoretical uncertainties. Resummed calculations can reach a higher logarithmic accuracy, but have been restricted to single observables. In a recent breakthrough, I constructed a new effective field theory that simultaneously achieves higher logarithmic accuracy in two independent observables, by factorizing the physics at the corresponding scales. Moving beyond this prototypical study, I will develop the general effective field theory framework that accounts for the relevant scales in realistic measurements, which overcomes the limitations of all three paradigms. This research will be carried out in the context of several important LHC applications: precision Higgs measurements, jet substructure techniques for identifying boosted heavy particles and supersymmetry searches. My new field-theoretic insights and more precise predictions will be critical as the LHC starts Run 2, searching for new physics at even higher energies.

Mots-clés : scet,factorization,resummation,precision,higgs,jets,jet substructure,supersymmetry,effective field theory,scales,renormalization group evolution
Projet ERC : CaBiS (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Life Science
Panel : Molecules of Life: Biological Mechanisms, Structures and Functions
Entité participante : Uppsala University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1494880.0 €

My proposal aims to take advantage of my ground-breaking finding that it is possible to mature, or activate, the [FeFe] hydrogenase enzyme (HydA) using synthetic mimics of its catalytic [2Fe] cofactor. (Berggren et al, Nature, 2013) We will now explore the chemistry and (bio-)technological potential of the enzyme using an interdisciplinary approach ranging from in vivo biochemical studies all the way to synthetic model chemistry. Hydrogenases catalyse the interconversion between protons and H2 with remarkable efficiency. Consequently, they are intensively studied as alternatives to Pt-catalysts for these reactions, and are arguably of high (bio-) technological importance in the light of a future “hydrogen society”. The project involves the preparation of novel “artificial” hydrogenases with the primary aim of designing spectroscopic model systems via modification(s) of the organometallic [2Fe] subsite. In parallel we will prepare in vitro loaded forms of the maturase HydF and study its interaction with apo-HydA in order to further elucidate the maturation process of HydA. Moreover we will develop the techniques necessary for in vivo application of the artificial activation concept, thereby paving the way for a multitude of studies including the reactivity of artificial hydrogenases inside a living cell, but also e.g. gain-of-function studies in combination with metabolomics and proteomics. Inspired by our work on the artificial maturation system we will also draw from our knowledge of Nature’s [FeS] cluster proteins in order to prepare a novel class of “miniaturized hydrogenases” combining synthetic [4Fe4S] binding oligopeptides with [2Fe] cofactor model compounds. Our interdisciplinary approach is particularly appealing as it not only provides further insight into hydrogenase chemistry and the maturation of metalloproteins, but also involves the development of novel tools and concepts applicable to the wider field of bioinorganic chemistry.

Mots-clés : biomimetic chemistry,bioinorganic chemistry,hydrogenases
Projet ERC : DIALOY (Horizon 2020, appel 2015, 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 : 1525000.0 €

My recent discoveries show that mosaic loss of chromosome Y (LOY) in peripheral blood is associated with increased risks of cancer and Alzheimer’s disease (AD). These conditions are responsible for >50% of morbidity/mortality in aging men. More than 15% of men older than 70 show some degree of LOY and these men survive on average only half as long as men without LOY. Smoking is strongly associated with LOY and remarkably, the fraction of cells with LOY decreases after cessation of smoking. Cells with LOY can be detected, and disease risks predicted, many years before clinical manifestation of disease. These results of associations between LOY, cancer and smoking have been published in Nature Genetics and Science during 2014. The overall objective of the proposal is to develop LOY as a new, strong and predictive biomarker. To this end, the research program focuses on three objectives: 1) expanding the study of LOY and associations with disease risks in still larger cohorts; 2) investigating functional aspects of LOY; and 3) develop improved technology for LOY-detection. The successful execution of the project is essential before LOY-testing in clinics can be realized. Diagnosis of cancer and AD in modern medicine is based on clinical symptoms of disease. Through earlier identification of individuals at increased risk for disease, preventive strategies could be applied, before the severe stages appear. Preliminary results affirm the feasibility of the project and provide proof-of-concept that LOY-tests can be used for early identification of men with increased risks for these diseases. In addition to improving diagnostics and therapeutics; implementation of LOY-testing could prevent smoking-related disease and reduce the health care costs. In the end, LOY-testing could decrease male mortality rates and possibly eliminate the sex-difference in life expectancy. The project will therefore benefit individual patients as well as healthcare systems and society at large.
Projet ERC : PROPHECY (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
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 : 1498625.0 €

My recent findings revealed translation of numerous previously unidentified (small) open reading frames and expression of alternative N-terminal proteoforms when studying bacterial translation. This proposal aims at unraveling the repertoire of bacterial pathogen proteoforms employed to establish a successful infection in a mammalian host cell. While deep sequencing has enabled the study of gene expression at the transcript level in both pathogen and host simultaneously, the depth of sequencing has so far proven to be unsatisfactory. Moreover, the study of bacterial proteome changes upon infection remains highly unexplored because of the higher proteome complexity of the host cell compared to the pathogen. These challenges clearly stresses the need for novel strategies based on complementary proteogenomics approaches enabling translation control studies in bacterial pathogens in a host context . I here propose the development and application of a complementary cutting-edge proteogenomic toolset which will enable for the first time targeted systematic genome- and proteome-wide surveys of bacterial transcriptional and translational activity during actual host cell infection. This ambitious endeavor will lead to: I) Establishment of dual Ribo-seq that allows the selective isolation of host or bacterial ribosomes, enabling to study the bacterial translatome in a host cell context. II) Development of tailored proteomics strategies permitting the selective isolation of (nascent) bacterial protein N-termini and enrichment of bacterial small ORF-encoded polypeptides (SEPs). Further, proteome-wide subcellular localization and protein stability studies will provide a dynamic view on bacterial protein expression. II) Bacterial proteoform interaction maps by the development of an innovative proxeome strategy. The identification of new pathogen virulence factors will contribute to the development of therapeutics and diagnostics for multiple models of infectious diseases.

Mots-clés : proteogenomics,gene annotation,small  open reading frames,proteoforms
Projet ERC : BEAM-EDM (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Fundamental constituents of matter
Entité participante : University of Bern — Pays : Suisse — Rôle : PI
Acronyme de l'entité : UB
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1404062.0 €

My research encompasses the application of novel methods and strategies in the field of low energy particle physics. The goal of the presented program is to lead an independent and highly competitive experiment to search for a CP violating neutron electric dipole moment (nEDM), as well as for new exotic interactions using highly sensitive neutron and proton spin resonance techniques. The measurement of the nEDM is considered to be one of the most important fundamental physics experiments at low energy. It represents a promising route for finding new physics beyond the standard model (SM) and describes an important search for new sources of CP violation in order to understand the observed large baryon asymmetry in our universe. The main project will follow a novel concept based on my original idea, which plans to employ a pulsed neutron beam at high intensity instead of the established use of storable ultracold neutrons. This complementary and potentially ground-breaking method provides the possibility to distinguish between the signal due to a nEDM and previously limiting systematic effects, and should lead to an improved result compared to the present best nEDM beam experiment. The findings of these investigations will be of paramount importance and will form the cornerstone for the success of the full-scale experiment intended for the European Spallation Source. A second scientific question will be addressed by performing spin precession experiments searching for exotic short-range interactions and associated light bosons. This is a vivid field of research motivated by various extensions to the SM. The goal of these measurements, using neutrons and protons, is to search for additional interactions such new bosons mediate between ordinary particles. Both topics describe ambitious and unique efforts. They use related techniques, address important questions in fundamental physics, and have the potential of substantial scientific implications and high-impact results.

Mots-clés : fundamental neutron physics,electric dipole moment,exotic interactions,spin precession,ramsey method,proton nuclear magn  resonance,cp violation,axion like particles,baryon asymmetry
Projet ERC : DynaMO_TB (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2000000.0 €

Mycobacterium tuberculosis (Mtb) is a very successful intracellular pathogen: in 2014, tuberculosis (TB) caused 1.5 million human deaths (World Health Organisation). To cause disease and disseminate to other hosts, Mtb needs to replicate within human cells. In spite of its enormous relevance for TB pathogenesis, the precise sites of Mtb replication in host cells remain unknown. This surprising gap in knowledge is in part due to the lack of appropriate imaging technologies that have precluded comprehensive understanding of the fundamental biology that underpins Mtb-host cell interactions critical to design rational interventions. Here, we propose to use a series of cutting-edge imaging approaches in human macrophages to: (1) define how the dynamic interactions between Mtb populations and organelles impact Mtb replication; (2) identify critical host and bacterial components that regulate Mtb replication and (3) characterise the host cell death pathways that control Mtb replication. For this, we will benefit from technologies developed in our group to image and quantify Mtb localisation and replication, such as live cell imaging, super resolution (SR) microscopy and correlative live cell 3D- electron microscopy (CLEM). We will refine these approaches to challenge the current limits of cell-based, high content imaging by combining human stem cell-derived macrophages with adhesive micropattern technologies for single cell analysis; this allows us to identify where and when Mtb replicate and how the interplay between host cells and Mtb impacts this process. Together, this proposal can uncover novel cellular pathways defining the intracellular sites that allow or restrict Mtb replication in human macrophages, thereby advancing the fields of both cell and infection biology. The characterization of the site of intracellular replication of Mtb can open avenues for a deeper understanding of human TB pathogenesis and facilitate development of vaccines and antibioo be here soon
Projet ERC : ECOEVODRTB (Horizon 2020, appel 2019, Advanced grants)
Domaine scientifique : Life Science
Panel : Environmental Biology, Ecology and Evolution
Entité participante : National Center for Tuberculosis and Lung Disease — Pays : Géorgie — Rôle : Partner
Acronyme de l'entité : NCTBLD
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 573375.0 €

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), is the main cause of human deaths due to infection in general, and to antimicrobial resistance in particular. Little is known on the within-host evolution of Mtb. Theory predicts that in chronic infections like TB, short-sighted evolution operates in the light of a trade-off between virulence and transmission. This trade-off is particularly relevant in the context of drug resistance, given the fitness costs of resistance. However, the role of short-sighted evolution in TB has never been explored empirically. Theory and model systems further predict that phenotypic drug tolerance facilitates the emergence of drug resistance, but the relevance of phenotypic drug tolerance for drug resistance evolution in the clinic has not been established for TB or any other bacterial disease. To address these and related questions, I propose to build on my recent work on the transmission of drug-resistant Mtb with a new focus on the within-patient evolution of drug-resistant Mtb and its link to between-patient evolution during transmission. Specifically, I shall: 1) Define the genomic characteristics and evolutionary forces shaping multidrug-resistant Mtb populations in individual patients over time and across different body compartments; 2) Compare the genomic and phenotypic properties of multidrug-resistant Mtb populations in individual patients to those circulating within the corresponding patient population; 3) Determine the effect of suboptimal patient treatment and phenotypic drug tolerance on drug resistance evolution in Mtb inside patients. By combining population genomics of Mtb sampled sequentially and from surgical specimens with experimental evolution and phenotypic characterization of clinical and experimentally evolved strains, this project will generate new insights relevant to both basic science and global public health.

Mots-clés : ecology,evolution,fitness,tuberculosis,mycobacteria,genomics,epidemiology,antibiotics,resistance,tolerance,persistence
Projet ERC : CardiacStroma (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Kantonsspital St. Gallen — Pays : Suisse — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2424000.0 €

Myocarditis is an acute inflammatory heart disease that can progress to chronic cardiomyopathy and heart failure. Since there is no specific treatment recommendation available for myocarditis and subsequent inflammatory cardiomyopathy, there is an urgent need to dissect the pathological principles underlying cardiac inflammation and to target those molecular pathways that are at the core of the pathological process. My recent research places cross-reactive CD4+ T cells at the center of inflammatory cardiomyopathy pathogenesis. The activation and sustenance of cardiotropic T cells is controlled in immune cell-nurturing niches that are generated by fibroblastic stromal cells through the provision of tissue cytokines of the TGF-beta superfamily. The overarching goal of this project is therefore to decipher the molecular pathways that govern the interaction of immune cells with stromal cells in the cardiac tissue through the combination of state-of-the-art pre-clinical models, novel methods from quantitative systems biology, functional validation by antibody blockade, and assessment of the translational relevance through the analysis of cardiac biopsies from human patients. The generation of antibodies that neutralize a distinct set of tissue cytokines or their inhibitors will not only serve as functional validation, but will open possibilities for future translational development. Moreover, the utilization of spatial transcriptomics for the analysis of human heart samples will open new avenues for innovative research both in immunology and in cardiology. Overall, I expect that the planned research program will deliver (i) novel targets for the treatment of myocarditis and inflammatory cardiomyopathy, (ii) validated prototype antibodies that ameliorate cardiac inflammation through the manipulation of stromal cell-immune cell interaction, and (iii) a comprehensive analysis of the changes in the cellular and molecular landscape during cardiac inflammation in humans.

Mots-clés : fibroblastic stromal cells,myocarditis,inflammatory cardiomyopathy,cd4 t cells