Objetivo Programmed cell death is essential for homeostasis, and its deregulation contributes to human disease. Inflammasome-induced pyroptosis of infected macrophages contributes to host defense against infections, but the concomitant release of inflammatory danger signals and leaderless cytokines is detrimental in chronic inflammatory diseases. The central hypothesis of the PyroPop ERC Consolidator project is that inflammasomes are cytosolic platforms that couple pathogen sensing to multiple programmed cell death modes. This is based on our preliminary data showing that inflammasomes can be triggered to switch from inflammatory pyroptosis to programmed necrosis and non-inflammatory apoptosis. This suggests that the (patho)physiological outcomes of inflammasome activation may be modulated for therapeutic purposes. However, the molecular machinery and effector mechanisms of pyroptosis, inflammasome-induced apoptosis and programmed necrosis are virtually unknown. My objectives are (i) to explore the cleavage events and subcellular dynamics of pyroptosis by proteomics and high-resolution time-lapse microscopy; (ii) to clarify the molecular mechanisms of pyroptosis and inflammasome-controlled cell death switching; and (iii) to address how inflammasome-associated cell death modes impact on anti-bacterial host defense and chronic inflammatory pathology in vivo through the identification of pyroptosis-selective biomarkers and clinical analysis of pyroptosis-deficient mouse models. The central hypothesis in this regard is that inflammasome-mediated secretion of leaderless cytokines (such as IL-1β and IL-18) and danger signals may be mechanistically coupled to pyroptosis, but not apoptosis induction. By clarifying the mechanisms of inflammasome-controlled programmed cell death, this project may set the path for the development of an entirely novel class of inflammation-modulating therapies that are based on converting inflammatory pyroptosis into non-inflammatory apoptosis. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health scienceshealth sciencesinflammatory diseasesnatural sciencesphysical sciencesopticsmicroscopymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasis Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-CoG-2015 - ERC Consolidator Grant Convocatoria de propuestas ERC-2015-CoG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-COG - Consolidator Grant Institución de acogida UNIVERSITEIT GENT Aportación neta de la UEn € 592 586,21 Dirección SINT PIETERSNIEUWSTRAAT 25 9000 Gent Bélgica Ver en el mapa Región Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 592 586,21 Beneficiarios (3) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo UNIVERSITEIT GENT Bélgica Aportación neta de la UEn € 592 586,21 Dirección SINT PIETERSNIEUWSTRAAT 25 9000 Gent Ver en el mapa Región Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 592 586,21 VIB VZW La participación finalizó Bélgica Aportación neta de la UEn € 676 229,16 Dirección SUZANNE TASSIERSTRAAT 1 9052 ZWIJNAARDE - GENT Ver en el mapa Región Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 676 229,16 JANSSEN PHARMACEUTICA NV Bélgica Aportación neta de la UEn € 729 099,63 Dirección TURNHOUTSEWEG 30 2340 Beerse Ver en el mapa Región Vlaams Gewest Prov. Antwerpen Arr. Turnhout Tipo de actividad Private for-profit entities (excluding Higher or Secondary Education Establishments) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 729 099,63