Objective
Chronic inflammation is causally linked to cancer development and most cancers contain an inflammatory infiltrate that is hijacked by tumour cells to promote angiogenesis, tissue invasion and cell proliferation. Moreover, autoimmune diseases with a huge social impact like rheumatoid arthritis are characterized by a chronic inflammatory state that is the main cause of damage and disability.
The transcription factors (TFs) of the NF-kB family are crucial regulators of acute and chronic inflammation, whose excessive activity is linked to tissue damage and survival of cancer cells. Drugs blocking NF-kB activation in a global manner are in clinical trials, but concerns about their safety have been raised because of the many physiological responses in which NF-kB is required. Conversely, therapies blocking the induction of subsets of NF-kB-regulated genes should provide restricted and predictable effects, but the molecular basis for their design are not available. The aim of this project is to identify and validate protein-protein interactions between NF-kB and transcriptional partners, which are required for target gene induction and amenable to small molecule-based perturbation.
We propose a rational combination of advanced technologies, including:
i) a genetic app roach to the identification of companion TFs and co-regulators required for induction of subsets of NF-kB target genes;
ii) in vivo analysis of co-occupancy of target genes by NF-kB and identified partners using chromatin immunoprecipitation;
iii) in vivo visualization of interactions using FRET on visible clusters of NF-kB-regulated genes;
iv) bioinformatics analysis and extraction of rules describing regulatory interactions.
The generation of a map linking protein-protein interactions to the induction of subsets of NF-kB-regulated genes will represent an essential tool in designing/screening drugs targeting NF-kB-dependent activities, and will provide new paradigms for "transcriptional therapies".
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine rheumatology
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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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.
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.
FP6-2005-MOBILITY-8
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.
Coordinator
MILAN
Italy
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.