> Stages de M2 > Liste des stages proposés pour l’année 2013-2014 > Role of Lipin 1 in the skeletal muscle development and function in the (...)

Role of Lipin 1 in the skeletal muscle development and function in the context of rhabdomyolysis

proposé par Mario Pende, Contrôle de la croissance cellulaire par les nutriments INSERM Faculté de Médecine — Université Paris Descartes Paris

Projet de stage : In humans, Lipin1 deficiency may cause a severe myopathy with signs of rhabdomyolysis. Fever, inflammation, starvation, exercise are among the triggering factors caysing muscle stress and precipitating the pathological features. The cause of the disease remains mysterious, though it is likely due to an uncharacterized metabolic and energetic defect. Lipin1 is a phosphatidic acid phosphatase intervening in lipid biosynthesis. Moreover, in starvation conditions, Lipin1 can also translocate in the nucleus where it acts as transcriptional regulator for a number of genes involved in energy metabolism. In our research proposal, the student will use state of the art techniques to evaluate gene expression, signal transduction, muscle physiology, metabolism in a series of in vitro and in vivo models : human muscle cells and biopsies from patients, whole body mouse and rat mutants, muscle specific mouse mutants. The overall aim is : i) to study the mechanisms leading to deregulated metabolism, muscle wasting, myopathy and rhabdomyolysis in specific environmental conditions causing muscle stress. ii) to evaluate the role of mTOR in this process iii) to propose therapeutical strategies using diet regimens or pharmacological agents that may alleviate the disease in patients

Techniques mises en œuvre par le stagiaire :
 Biologie moléculaire, Western Blot, Quantitative RT-PCR, Culture de cellules primaire de myoblastes, Etudes histologiques standards, immunomarquages…

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