Objective 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. Fields of science 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) Topic(s) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Call for proposal ERC-2013-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution UNIVERSITAETSKLINIKUM FREIBURG EU contribution € 541 715,75 Address HUGSTETTER STRASSE 49 79106 Freiburg Germany See on map Region Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Gerhard Henninger (Mr.) Principal investigator Olaf Groß (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITAETSKLINIKUM FREIBURG Germany EU contribution € 541 715,75 Address HUGSTETTER STRASSE 49 79106 Freiburg See on map Region Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Gerhard Henninger (Mr.) Principal investigator Olaf Groß (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN Germany EU contribution € 953 817,25 Address ISMANINGER STRASSE 22 81675 Muenchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Beate Schaulin (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data