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 (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine endocrinology diabetes
- natural sciences physical sciences optics microscopy
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2013-StG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
79106 Freiburg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.