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> Stages de M2 > Liste des stages proposés pour l’année 2017-2018 > 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, Necker Enfants Malades Institute (INEM),CS61431, 75993 Paris cedex 14

Projet de stage : The proposed M2 project is a part of on-going research in our laboratory that aims to elucidate molecular mechanisms of growth control in mammals. It will focus on class III PI3K. Despite its essential role in endocytosis, autophagy and lysosomal function, the functions and the regulation of of class III in vivo are still poorly understood. Recent works of our team demonstrated a key role of class III PI3K in the whole body metabolic homeostasis (Nemazanyy 2013, Nemazanyy 2015). However, there is a gap of knowledge on the involvement of class III PI3K in a control of specific metabolic activities and whether those underlign human pathology(ies). Our recent analyses revealed striking mitochondrial depletion in PI3K-III mutants that made us hypothesise that class III PI3K might also function upstream of mitochondria, a completely novel and unexplored aspect of class III PI3K biology. We are looking for an enthusiastic scientifically driven M2 trainee with a strong interest in signalling, metabolism and pathophysiology to join our team to contribute to the project that aims to reveal how class III PI3K controls mitochondria function and how these finding could be explored as a therapy in human disease. As M2 trainee, you will be integrated in the team to : (1) conduct studies of mitochondria activity and maintenance in mutants of class III PI3K ; (2) rescue mitochondrial defects using pharmacological and gene targetting approaches in class III PI3K deficient cells ; (3) characterise class III PI3K activities in animal models and patient samples of metabolic and lysosomal storage disease to propose novel therapeutic approaches. You will be trained in a highly dynamic scientifically stimulating international English-French working language environment hand in hand with fellows from all over the world (France, Italy, USA, China, Japan, Lebanon and Ukraine). The host laboratory is a part of a newly formed multidisciplinary international research Centre in Molecular Medicine-Institut Necker Enfants Malades (INEM) which emerged on a crossroad of fundamental, translational and clinical research. Techniques mises en œuvre par le stagiaire : You will work on the independent (though guided) research program under a mentorship of Dr. Ganna Panasyuk. You will master different wet lab molecular biology techniques including RNA/protein extraction, qPCR, immunoblot, fluorescent microscopy, metabolomics approaches using masspectrometry and SeaHorse measurements, gene therapy approaches, will work with mouse models and in vitro models (primary and established cell cultures of hepatocytes and muscle cells, mutant cell lines generated using CRISPR-Cas9 approach).

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