Obiettivo Inflammasomes are intracellular danger-sensing protein complexes that are important for host protection. They initiate inflammation by controlling the activity of the proinflammatory cytokine interleukin-1β (IL-1β). Unlike most other cytokines, IL-1β is produced and retained in the cytoplasm in an inactive pro-form. Inflammasome-dependent maturation of proIL-1β is mediated by the common component of all inflammasomes, the protease caspase-1. Caspase-1 also controls the secretion of IL-1β, but the mechanism and route of secretion are unknown. We have recently demonstrated that the ability of caspase-1 to control IL-1β secretion is not dependent on its protease activity, but rather on a scaffold or adapter function of caspase-1. Furthermore, we and others could show that caspase-1 can control the secretion of non-substrates like IL-1α. These insights provide us with new and potentially revealing means to investigate the downstream effector functions of caspase-1, including the route and mechanism of IL-1 secretion. We will develop new tools to study the process of IL-1 secretion by microscopy and the novel mode-of-action of caspase-1 through the generation of transgenic models.Despite the important role of IL-1 in host defence against infection, dysregulated inflammasome activation and IL-1 production has a causal role in a number of acquired and hereditary auto-inflammatory conditions. These include particle-induced sterile inflammation (as is seen in gout and asbestosis), hereditary periodic fever syndromes, and metabolic diseases like diabetes and atherosclerosis. Currently, recombinant proteins that block the IL-1 receptor or deplete secreted IL-1 are used to treat IL-1-dependent diseases. These are costly treatments, and are also therapeutically cumbersome since they are not orally available. We hope that a better understanding of caspase-1-mediated secretion of IL-1 will unveil mechanisms that may serve as targets for future therapies for these diseases. Campo scientifico medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesphysical sciencesopticsmicroscopy Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Invito a presentare proposte ERC-2013-StG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante UNIVERSITAETSKLINIKUM FREIBURG Contributo UE € 541 715,75 Indirizzo HUGSTETTER STRASSE 49 79106 Freiburg Germania Mostra sulla mappa Regione Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Gerhard Henninger (Mr.) Ricercatore principale Olaf Groß (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITAETSKLINIKUM FREIBURG Germania Contributo UE € 541 715,75 Indirizzo HUGSTETTER STRASSE 49 79106 Freiburg Mostra sulla mappa Regione Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Gerhard Henninger (Mr.) Ricercatore principale Olaf Groß (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN Germania Contributo UE € 953 817,25 Indirizzo ISMANINGER STRASSE 22 81675 Muenchen Mostra sulla mappa Regione Bayern Oberbayern München, Kreisfreie Stadt Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Beate Schaulin (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
