PROTEOFIT
Financiado
Adapting protein fate for muscle function and fitness
Muscle function is essential for motion, exercise, and shivering, whereas physical inactivity is causally related to reduced metabolic fitness in animal models and humans. A critical requirement for muscle function is that protein...
Muscle function is essential for motion, exercise, and shivering, whereas physical inactivity is causally related to reduced metabolic fitness in animal models and humans. A critical requirement for muscle function is that proteins are properly produced and, if necessary, degraded to adapt the proteome to meet metabolic demands. However, there is a fundamental, open gap in understanding how challenges to muscle proteostasis are sensed and how protein fate is subsequently adapted to enhance muscle function in exercise or, conversely, how it is compromised in obesity. I hypothesize that protein fate is highly adaptive and can be fine-tuned to promote proteostasis, the integrity of muscle cells, and metabolic health. Identifying novel key regulators of these mechanisms in muscle may hold great therapeutic promise for targeting metabolic fitness to combat obesity and associated disorders. In this innovative project I want to define new mechanisms of muscle adaptation in humans and preclinical mouse models, with the ultimate goal of using this knowledge to improve muscle function and fitness in obesity. I will identify exercise- and obesity-specific substrates of the proteasome by ubiquitomics in human and mouse muscle and define how the ubiquitination and turnover of these proteins dictates muscle cell function. In a complementary approach, I will use novel loss- and gain-of-function mouse models allowing for precise muscle-specific manipulation of Nfe2l1, an adaptive regulator of proteasomal protein degradation, to define the biological and therapeutic significance of this pathway for muscle function in exercise and obesity. In summary, this novel work will provide a transformative molecular understanding of muscle adaption to metabolic challenges and provide insight into how this translates into metabolic fitness and the development of obesity and associated disorders in humans.
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Duración del proyecto: 66 meses
Fecha Inicio: 2019-11-25
Fecha Fin: 2025-05-31
Fecha Fin: 2025-05-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2019-11-25
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2019-STG:
ERC Starting Grant
Cerrada
hace 6 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
LUDWIGMAXIMILIANSUNIVERSITAET MUENCHEN
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
547.50K€ |
Participante