Objectif 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. Champ scientifique medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesphysical sciencesopticsmicroscopy Programme(s) 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) Thème(s) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Appel à propositions ERC-2013-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil UNIVERSITAETSKLINIKUM FREIBURG Contribution de l’UE € 541 715,75 Adresse HUGSTETTER STRASSE 49 79106 Freiburg Allemagne Voir sur la carte Région Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Type d’activité Higher or Secondary Education Establishments Contact administratif Gerhard Henninger (Mr.) Chercheur principal Olaf Groß (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITAETSKLINIKUM FREIBURG Allemagne Contribution de l’UE € 541 715,75 Adresse HUGSTETTER STRASSE 49 79106 Freiburg Voir sur la carte Région Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Type d’activité Higher or Secondary Education Establishments Contact administratif Gerhard Henninger (Mr.) Chercheur principal Olaf Groß (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN Allemagne Contribution de l’UE € 953 817,25 Adresse ISMANINGER STRASSE 22 81675 Muenchen Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Contact administratif Beate Schaulin (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée