Objective
The innate immune system evokes inflammation to control pathogens or damage. Sophisticated mechanisms interpret molecular triggers to activate inflammasomes or transcription of pro-inflammatory genes. While numerous autoinflammatory conditions underline the need to control inflammation, we still rely on simplistic models to understand its negative regulation. I hypothesize that an intricate signaling network interprets information to prevent or downregulate inflammation. Understanding these so far elusive processes demands radically new cell biology tools, which I will develop and apply in ‘DEFLAMMATION’.
I propose to define signaling hubs that integrate cellular input and coordinate effectors to actively downregulate inflammation where beneficial to the organism. To yield unprecedented molecular insights, we will apply nanobodies to inhibit protein function, manipulate post-translation modifications, and visualize endogenous proteins and their binary interactions. I hypothesize that two poorly understood members of the NLR family, NLRC3 and NLRX1, act as signaling hubs that coordinate negative regulation of pro-inflammatory gene expression. No such coordinator is known for inflammasomes. In objective 1, we will pinpoint how NLRC3 controls inflammation and T cell activity. I hypothesize that NLRC3 forms anti-inflammatory signalosomes to control the ubiquitination status of pro-inflammatory signaling components. In objective 2, we will reveal how NLRX1 counteracts interferon responses, inflammation, and proliferation. We will explore whether NLRX1 activation coordinates organelle-specific autophagy to remove pro-inflammatory signaling complexes. In objective 3, we will identify novel regulatory circuits that control inflammasome activation using CRISPR/Cas9 and cDNA screens, taking advantage of a novel reporter we have developed.
The anticipated results will reveal entirely new layers of regulation of inflammation with implications for therapeutic interventio
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.
You need to log in or register to use this function
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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.
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.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
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.
(opens in new window) ERC-2023-COG
See all projects funded under this callHost institution
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
53127 Bonn
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.