Objective Pyroptosis is a highly inflammatory form of cell death that drives host protection against intracellular pathogens. Pyroptosis is initiated by inflammasome-activated inflammatory caspases (e.g. caspase-1/4/5/11), which cleave gasdermin D to trigger plasma membrane pores. In contrast, apoptosis is driven by apoptotic caspases (e.g. caspase-3/7/8/9), and is traditionally classified as an immunologically silent form of cell death that is important for development and maintenance of homeostasis. However, emerging studies suggest that caspase-8 activation during extrinsic apoptosis promotes inflammation by triggering the assembly of a proinflammatory, multi-protein complex called the NLRP3 inflammasome, through an ill-defined mechanism. A recent study identified a caspase-3 cleavage site within gasdermin D; cleavage of gasdermin D by apoptotic caspase-3 suppresses the cytotoxic function of this protein. These suggest a complex crosstalk between the pyroptosis and apoptosis. Therefore, the aim of this project is to investigate 1) novel proinflammatory functions of gasdermin D during extrinsic apoptosis; 2) the role of gasdermin D in caspase-8-dependent NLRP3 activation; and 3) the importance of caspase-3-mediated gasdermin D inactivation at steady state in vivo and during chemotherapy. This project will greatly enhance the skills and competence of the experienced researcher through advanced training and international mobility, and is in line with Horizon 2020 Work Programme objective. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITE DE LAUSANNE Net EU contribution € 191 149,44 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
