Objective
BACKGROUND: There is a tremendous need to develop novel therapies for heart failure. In particular, sustained pathological hypertrophy, a major predictor of this condition, is a complex process, which involves transcriptional and posttranscriptional regulation of the cardiac genome. There is now clear indication that, besides a few known transcriptional regulators, multiple, still poorly understood cardiac factors are involved in hypertrophy; understanding this complexity is expected to pave to the way to innovative therapies. In particular, recent data demonstrate that dysregulated microRNAs (miRs) are associated with heart failure, and that selective modulation of miRs can provide therapeutic benefits. Our pilot-data show that expression of the miR-106b~25 cluster decreases during pathological hypertrophy in mice and that virus-mediated overexpression of this cluster prevents phenylephrine-induced hypertrophic remodeling. Following bioinformatics screens for potential direct downstream targets of the miR-25~106b cluster, we identified a series of transcription factors, which might play a role in pathological cardiac remodeling.
AIM: To define the functional implication of the miR-106b~25 cluster in pathological cardiac hypertrophy and to exploit this information towards the development of novel therapeutic approaches.
APPROACH: We will identify direct downstream targets of the miR-106b~25 cluster during hypertrophy, by performing Ago2-Immunoprecipitation and by treating neonatal cardiomyocytes with precursors of miR-25, miR-93 and miR-106b, followed by next generation sequencing (Objective 1); We aim to reverse pathological cardiac remodeling and prevent heart failure by delivery of recombinant adeno-associated virus (rAAV9)- miR-106b~25 in mice (Objective 2). The results obtained will generate important intellectual property value and will constitute the basis for further development towards the generation of novel therapies against heart failure.
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.
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine cardiology
- natural sciences biological sciences genetics genomes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IEF
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Funding Scheme
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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
34149 Trieste
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.