Date : 23/4/2010
Internship proposal for : Master 1 or Master 2
Laboratory
Cell growth control by nutrients
U845 INSERM
156 rue de Vaugirard 1er etage 75015 Paris
Director : Gerard iFriedlander
Website : http://u845.necker.fr/recherche/presentation-des-equipes/6.-m-pende/
Main discipline : Molecular biologyMolecular biology
Supervisor
Mario Pende
email :
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phone : +33 140615315
Subjects / Tools-Methodologies
1 : signal transduction/microarrays
2 : cell growth/bioinformatics
3 : translation/polysomal fractionation
Summary of lab's interests
Mammalian growth and metabolism are controlled by extracellular signals, such as insulin and insulin-like growth factors (IGFs). Depending on nutrient availability, these factors regulate the size and number of cells and the synthesis of lipids, proteins and sugars. The aim of the research program is to determine if these responses are coordinated or if they are relayed by independent intracellular signaling pathways. Target Of Rapamycin (TOR) is an evolutionary conserved protein kinase that plays a central role in the integration of growth factor and nutrient signals. The overall goal of the lab is: - to identify the mTOR targets involved in cell growth, proliferation and metabolic control - to evaluate the impact of mTOR deregulation on human patients and mouse models of disease, with special focus on cancer, type 2 diabetes, myopathy and obesity.
Summary of project
The Target Of Rapamycin (TOR) signalling pathway has a conserved role during evolution in the control of cell growth according to nutrient availability. Protein synthesis is a fundamental step in the anabolic response of a cell. However, the molecular mechanisms downstream of TOR that control protein synthesis are still poorly understood. One of the substrates of TOR are S6K protein kinases that phosphorylate the ribosomal protein S6. It is likely that this change affects ribosome activity, but we do not yet know its function. The student will determine the RNA differentially translated in cells derived from wild mice and S6K1, 2 - / - by fractionation of polysomes followed by microarray analysis. Data will be validated by quantitative RT PCR. mRNA classes will be identified by bioinformatic analysis Techniques: Extraction of mouse tissues/cell cultures, Polysome Profiles, Microarray, QRTPCR, bioinformatics