Objective
The innate immunity constitutes an efficient barrier by rapidly detecting pathogens and tissue damages through pattern recognition receptors including NLRP3. On the other hand, inappropriate NLRP3 activation causes deleterious inflammation and contributes to various conditions including atherosclerosis, diabetes, gout and Alzheimer's diseases. Therefore NLRP3 requires tight regulation that remains poorly characterized. Activated NLRP3 assembles a multimeric inflammasome complex serving as activation platform for caspase-1 that controls processing and release of cytosolic cytokines including IL-1β. We recently evidenced that inflammasome assembly requires NLRP3 deubiquitination by the deubiquitinase BRCC3. The aim of this proposal is to decipher this new ubiquitin-dependent regulatory pathway critical for NLRP3 activation. We propose to identify stimuli, signaling pathways and enzymatic complexes controlling NLRP3 ubiquitination level. Using both cell biology and biochemistry approaches, we will decipher the molecular mechanisms beneath the regulation of the deubiquitinase and ubiquitin ligase complex activity, as well as the loss of activity of ubiquitinated NLRP3. Lastly, we will test the in vivo relevance of NLRP3 ubiquitination using both mouse models, patients study and pharmacological approach. Altogether, this project will thoroughly characterize this new pathway controlling inflammasome activity and provide new therapeutic targets against inflammation related diseases that are highly prevalent in the European Union.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine neurology dementia alzheimer
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences cell biology
- medical and health sciences clinical medicine endocrinology diabetes
- natural sciences computer and information sciences artificial intelligence pattern recognition
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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-CoG
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
75654 PARIS
France
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.