Objective
MicroRNAs (miRNAs) negatively regulate gene expression by promoting mRNA degradation and inhibiting mRNA translation. Recent studies have uncovered key roles of miRNAs as mediators of cardiovascular development and disease, but much remains to be learned about their mechanisms of action and regulation. Dr. Olson's lab has described a family of muscle-specific miRNAs, referred to as MyomiRs, which are encoded by introns of myosin heavy chain genes. These three miRNAs (miR-208a, miR-208b, miR-499) control pathological cardiac remodeling, muscle myosin content, myofiber identity, and muscle performance. Each of these miRNAs regulates the expression of Sox6, a transcriptional repressor. Consistent with a role for Sox6 as a mediator of the actions of MyomiRs, over-expression of Sox6 in skeletal muscle mimics the effects of MyomiR gene deletion and deletion of Sox6 in skeletal muscle recapitulates the phenotype of MyomiR over-expression. These findings have revealed a previously unrecognized role for Sox6 as a mediator of skeletal muscle gene expression, but nothing is known of its potential role in the control of cardiac gene expression or function. Given the importance of MyomiRs in regulating cardiac stress responses, and the regulation of Sox6 expression by MyomiRs, we postulate that Sox6 is a central regulator of cardiac hypertrophy and heart failure. The goal of this project is to define the mechanisms whereby Sox6 controls cardiac gene expression by idenfication of its downstream target genes and transcriptional cofactors and to explore its role as a mediator of the actions of myosin-encoded cardiac miRNAs. The project will benefit from a strong foundation of preliminary data and unique mouse strains (e.g. Sox6 knockout and transgenic mice) already established in the lab. These studies promise to provide important new insights into the gene regulatory mechanisms in heart disease and to potentially reveal new therapeutic targets for modulation of cardiac function.
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.
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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-2010-IOF
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
79106 Freiburg
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.