Objective
Toll-like receptors (TLRs) are key microbial sensors essential for the development of innate immunity to pathogens[1]. TLR activation induces the expression of inflammatory cytokines, antimicrobial proteins, and regeneration factors. Uncontrolled activation of TLRs leads to the development of fatal inflammatory diseases. TLR activation is tightly controlled to ensure that repeated activation does not lead to sustained activation of target genes - a phenomenon termed TLR-tolerance. Lipopolysaccharide-(LPS)-tolerance applies primarily to inflammatory cytokines but not antimicrobial proteins. Selective inactivation of inflammatory genes, but not antimicrobial genes ensures the host’s ability to continuously build up antimicrobial defences without causing fatal inflammatory responses.
I recently discovered that Bcl-3 mediates LPS-tolerance by inhibiting the activity of NF-kappaB, a major LPS-activated transcription factor. In the absence of Bcl-3, an inhibitory NF-kappaB complex is degraded, the inflammatory response exacerbated and LPS-tolerance abolished. NF-kappaB-binding sites are significantly enriched among tolerisable (inflammatory) genes. I hypothesise that the NF-kappaB binding site of a promoter dictates sensitivity to TLR-tolerance and that Bcl-3-mediated suppression of TLR signaling applies to inflammatory but not antimicrobial genes. The proposed research will test these hypotheses and investigate the underlying molecular mechanisms of Bcl-3-and NF-kappaB-mediated tolerance.
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 health sciences inflammatory diseases
- natural sciences biological sciences biochemistry biomolecules proteins
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
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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.
FP7-PEOPLE-IRG-2008
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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.
Coordinator
T12 YN60 Cork
Ireland
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.