Obiettivo 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. Campo scientifico medical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencescomputer and information sciencesartificial intelligencepattern recognition Parole chiave InflamCellDeath Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2017-COG - ERC Consolidator Grant Invito a presentare proposte ERC-2017-COG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante UNIVERSITE DE LAUSANNE Contribution nette de l'UE € 1 999 176,00 Indirizzo Quartier Unil-Centre Bâtiment Unicentre 1015 Lausanne Svizzera Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Région lémanique Vaud Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 999 176,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto UNIVERSITE DE LAUSANNE Svizzera Contribution nette de l'UE € 1 999 176,00 Indirizzo Quartier Unil-Centre Bâtiment Unicentre 1015 Lausanne Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Région lémanique Vaud Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 999 176,00