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> Stages de M2 > Liste des stages proposés pour l’année 2016-2017 > Molecular determinants of hepatic nutrient sensing and homeostasis

Molecular determinants of hepatic nutrient sensing and homeostasis

proposé par Dr. Ganna Panasyuk , Inserm U1151/CNRS UMR 8253, (INEM), 75993 Paris cedex 14

Projet de stage :

An evolutionary conserved Phosphoinositide 3-Kinase/mammalian Target Of Rapamycin (PI3K/mTOR) signalling pathway is essential for growth control and its activity is commonly deregulated in human pathologies. Work of our laboratory has contributed to the understanding of complex interplays in PI3K/mTOR signalling. We are looking for an enthusiastic scientifically driven individual with a strong interest in signalling, metabolism and pathophysiology to join our team to contribute to the project on investigation of the molecular mechanisms of class III PI3K (PI3K-III) regulation in liver. PI3K-III is present in every eukaryotic cell. Its activity is essential for endocytosis, autophagy and lysosomal function – major cellular pathways for nutrient acquisition and metabolism. Despite evolutionary conservation, we have a limited knowledge of PI3K-III functions and regulation in vivo. In our recent studies, we have revealed a novel crosstalk between insulin and PI3K-III signalling. We have also discovered an essential role of PI3K-III signalling in the whole body metabolic control suggesting that it might be implicated in human pathologies (Nemazanyy 2013, Nemazanyy 2015). As a M2 trainee, you will conduct the studies of PI3K-III expression and measurements of PI3K-III activity under physiological and pathophysiological conditions mimicking metabolic syndrome. Next, you will perform the functional studies to address the mechanisms of hepatic PI3K-III regulation. You will work in a highly dynamic scientifically stimulating English-French bilingual environment hand in hand with fellows from all over the world (including France, Italy, USA, China and Ukraine). The host laboratory is a part of a newly formed multidisciplinary international research Centre in Molecular Medicine-Institut Necker Enfants Malades (INEM) (http://www.institut-necker-enfants-malades.fr/index.php ?menu=team_view&faculty_id=5). INEM is a scientifically vibrant international institution which emerged on a crossroad of fundamental, translational and clinical research. Among the major strengths of INEM is an access to state-of-the-art facilities and a close link with the Necker hospital, one of the oldest and at the same time most innovative medical centres in France.

Techniques mises en œuvre par le stagiaire :

To fulfil described above scientific goals, you will combine different in vivo (mouse models) and in vitro (primary and established cell cultures) models ; gene therapy using viral vectors and pharmacological approaches. The M2 project will be a fully independent though supervised research program using an array of wet lab molecular biology techniques (e.g. RNA/protein extraction, qPCR, immunoblot, immunohistochemistry, fluorescent microscopy).

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