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Content archived on 2024-06-18

Coactivator-controlled transcriptional networks regulating skeletal muscle cell plasticity

Objective

Regular physical activity is linked to improved health and increased life expectancy. Inversely, a sedentary life-style is a strong and independent risk factor for many chronic diseases, including obesity, type 2 diabetes or cardiovascular disorders, as well as certain types of cancer or neurodegeneration. Interestingly however, the molecular mechanisms that mediate the health beneficial effects of exercise, or those that trigger the pathological changes in diseases, are largely unknown.
The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is one of the major regulatory hubs of muscle adaptation to endurance training. Accordingly, elevated expression of PGC-1α in muscle is sufficient to induce a trained phenotype in mice. Inversely, mice lacking a functional PGC-1α gene in skeletal muscle exhibit many signs of pathological inactivity. Finally, PGC-1α expression is dysregulated in pathological contexts in human muscle, including type 2 diabetes and aging. Therefore, the study of the regulation and function of PGC-1α in muscle has the potential to yield important insights into the molecular mechanisms that control muscle health.
Unfortunately, the characterization of PGC-1α is drastically hampered by the high complexity of the transcriptional network controlled by this coactivator protein, which binds to many different transcription factor binding partners in a cell context-specific manner. Moreover, PGC-1α seems to directly couple transcription to RNA processing, thereby further complicating the analysis of PGC-1α-controlled biological programs. Our proposal combines novel innovative experimental and biocomputational approaches with the physiological study of healthy and diseased muscle cells ex vivo and in different animal models targeted on PGC-1α. Together, our findings will reveal novel insights on muscle function and may substantially shape the development of exercise mimetic-based therapies.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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ERC-2013-CoG
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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.

ERC-CG - ERC Consolidator Grants

Host institution

UNIVERSITAT BASEL
EU contribution
€ 1 999 396,80
Address
PETERSPLATZ 1
4051 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

No data

Beneficiaries (1)

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