Objective
Cholesterol and lipid homeostasis is achieved through the action of a complex regulatory network (regulome) that controls the expression of genes involved in these metabolic pathways.
Our recent studies suggest that:
i) high in the hierarchy of the regulatory network is the nuclear receptor HNF4, whose activity on cholesterol metabolism genes is selectively affected by HDAC7 recruitment, and that
ii) targeting HDAC7 lowers serum cholesterol levels.
Given this premise, the general objective of this proposal is to bridge these new basic science concepts to clinical applications by analysing the transcriptome and the regulome controlling cholesterol and lipid homeostasis and by pharmacologically targeting the HNF4/HDAC7 regulatory axis.
We will develop improved strategies for the prevention and treatment of atherosclerosis by pursuing the following specific aims:
1. Rational design of high affinity ligands for HNF4 and inhibitors of HDAC7 based on the analysis of their 3D-structures
2. Analysis of the global pattern of gene expression (Transcriptome) and transcription factor network (Regulome) involved in lipid homeostasis in control mice and in mice treated with HDAC inhibitors and HNF4 ligands and definition of their pharmacological profile
3. Development of clinical diagnostic tools
The multidisciplinary nature of the proposal will exploit and integrate the expertise in molecular/cell biology, pharmacology, toxicology, medicine, physics/crystallography, chemistry, biochemistry and bioinformatics to identify new molecules affecting lipid metabolism and study their effects on pathophysiological events underlying atherosclerosis.
Upon completion of the project we expect to:
a. identify HNF4 ligands and HDAC7 selective inhibitors affecting lipid metabolism
b. define the effects of these molecules on the transcription network regulating cholesterol and lipid metabolism and their pharmacological profile
c. develop non invasive tools for evaluating the atherosclerotic burden
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 clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine toxicology
- medical and health sciences basic medicine physiology homeostasis
- medical and health sciences basic medicine pharmacology and pharmacy
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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.
FP6-2005-LIFESCIHEALTH-6
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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
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.