Objectif Pyroptosis is a lytic pro-inflammatory type of programmed cell death that is induced by inflammatory caspases, a family of proteases that control the innate immune response to infection, injury or noxious substances. Inflammatory caspases are activated within so-called inflammasomes, cytosolic signalling platforms that are assembled by pattern recognition receptors upon the detection of pathogen- or host-derived danger signals. Pyroptosis is essential for antimicrobial host defense, but also promotes the concomitant release of inflammatory danger signals and leaderless cytokines that is detrimental during chronic inflammatory disease.Recently it was found that pyroptosis is caused by the cleavage of a single caspase substrate called gasdermin-D. This cleavage generates a cytotoxic N-terminal fragment of gasdermin-D that targets the plasma membrane, where it forms large permeability pores and thus causes pyroptotic cell death. Gasdermin-D is only one member of the larger gasdermin protein family, an emerging group of cell death effectors that share its pore-forming cytotoxic activity and that appear to be major regulators of inflammatory necrotic cell death.The main goal of this proposal is to comprehensively characterize the function of gasdermins in anti-microbial host defense, to investigate the consequences of gasdermin-D pore formation to the host cell and to elucidate the pathways that regulate gasdermin activation. My objectives are:1) to define the role of gasdermin-D in inflammasome-dependent anti-bacterial host defense2) to study the role of membrane repair in restricting gasdermin-D-induced membrane3) to characterize the function and regulation of other gasdermin family members during infectionBy characterizing the mechanism and function of gasdermin-induced cell death in host-defense and inflammation this project may contribute to the development of novel therapies for infectious as well as inflammatory diseases. Champ scientifique medical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencescomputer and information sciencesartificial intelligencepattern recognition Mots‑clés InflamCellDeath Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2017-COG - ERC Consolidator Grant Appel à propositions ERC-2017-COG Voir d’autres projets de cet appel Régime de financement ERC-COG - Consolidator Grant Institution d’accueil UNIVERSITE DE LAUSANNE Contribution nette de l'UE € 1 999 176,00 Adresse QUARTIER UNIL CENTRE - BATIMENT UNICENTRE 1015 LAUSANNE Suisse Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 999 176,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire UNIVERSITE DE LAUSANNE Suisse Contribution nette de l'UE € 1 999 176,00 Adresse QUARTIER UNIL CENTRE - BATIMENT UNICENTRE 1015 LAUSANNE Voir sur la carte Région Schweiz/Suisse/Svizzera Région lémanique Vaud Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 999 176,00
