Objective 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. Fields of science medical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencescomputer and information sciencesartificial intelligencepattern recognition Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-COG - ERC Consolidator Grant Call for proposal ERC-2017-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator UNIVERSITE DE LAUSANNE Net EU contribution € 1 999 176,00 Address Quartier unil-centre bâtiment unicentre 1015 Lausanne Switzerland See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITE DE LAUSANNE Switzerland Net EU contribution € 1 999 176,00 Address Quartier unil-centre bâtiment unicentre 1015 Lausanne See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
