> Stages de M1 > Stages proposés pour l’année 2015-2016 > Molecular mechanisms of nutrient sensing in liver

Molecular mechanisms of nutrient sensing in liver

Stage proposé par Gana Panasyuk

Inserm U1151/CNRS UMR 8253, Necker Enfants Malades Institute (INEM), Faculté de Médecine Paris Descartes, Leriche Building - Porte 9, 1st Floor - Lab-120/Office-128, 14 Rue Maria Helena Vieira da Silva, CS61431, 75993 Paris cedex 14, France

Projet de stage : situation du sujet, objectif du stage, approches expérimentales (une dizaine de lignes maximum)

Understanding of how metabolic activities are coordinated in response to nutrient availability is an enduring challenge. In physiology, those are taking place in everyday feeding-starvation cycles. Dysregulated nutrient sensing underlines numerous pathologies including metabolic disorders and cancer. Enzyme complex of class III phosphoinositide 3-kinase (PI3K-III) is essential for nutrient uptake and catabolism, through its control of endocytic trafficking, autophagy and lysosomal function. It is unknown if and how expression and activity of PI3K-III is controlled in response to nutrient availability in vivo. The proposed training will focus on studying how PI3K- III expression and activity is modified in the physiological cycles of starvation/feeding in mice. The successful candidate will be trained in highly dynamic scientifically stimulating international English-French bilingual environment. The expertise of the team is reflected in the publication track record and is recognised by the highest national evaluation and the financial support of numerous foundations.

Techniques mises en œuvre par le stagiaire : During the training student will be exposed to numerous approaches. He/She will learn and apply diverse techniques including experimenting with mice, primary cell cultures of hepatocytes, RNA preparation and quantitative RT-PCR, protein expression analysis by immunoblotting.

Publications du responsable de stage au cours des 5 dernières années : 1. Nemazanyy I, Montagnac G, Russell RC, Morzyglod L, Burnol AF, Guan KL, Pende M, Panasyuk G. Class III PI3K regulates organismal glucose homeostasis by providing negative feedback on hepatic insulin signalling. Nat Commun. 2015 6:8283. doi : 10.1038/ncomms9283. 2. Gentric G, Maillet V, Paradis V, Couton D, L’Hermitte A, Panasyuk G, Fromenty B, Celton-Morizur S and Desdouets C. Oxydative Stress Promotes Pathological Liver Polyploidization in NAFLD. J Clin Invest 2015 Jan 26. doi10.1172/JCU73957 3. Liang N, Zhang C, Dill P, Pansyuk G, Pion D, Koka V, Gallazzini M, Olson EN, Lam H, Henske EP, Dong Z, Apte U, Pallet N, Johnson RL, Terzi F, Kwiatkowski DJ, Scoazec JY, Martignoni G, Pende M. Regulation of YAP by mTOR and autophagy reveals a therapeutic target of tuberous sclerosis complex. J Exp Med. 2014 Oct 20 ;211(11):2249-63. 4. Nemazanyy I, Espeillac C, Pende M, Panasyuk G. Role of PI3K, mTOR and Akt2 signalling in hepatic tumorigenesis via the control of PKM2 expression. Biochem Soc Trans. 2013 Aug ;41(4):917-22. 5. Nemazanyy I, Blaauw B, Paolini C, Caillaud C, Protasi F, Mueller A, Proikas-Cezanne T, Russell RC, Guan KL, Nishino I, Sandri M, Pende M, Panasyuk G. Defects of Vps15 in skeletal muscles lead to autophagic vacuolar myopathy and lysosomal disease. EMBO Mol Med. 2013 Jun ;5(6):870-90. 6. Panasyuk G, Patitucci C, Espeillac C, Pende M. The role of the mTOR pathway during liver regeneration and tumorigenesis. Ann Endocrinol (Paris). 2013 May ;74(2):121-2. 7. Panasyuk G, Espeillac C, Chauvin C, Pradelli L, Horie Y, Suzuki A, Annicotte JS, Fajas L, Foretz M, Verdeguer F, Pontoglio M, Ferré P, Scoazec JY, Birnbaum MJ, Ricci JE, Pende M. PPARγ contributes to PKM2 and HK2 expression in fatty liver. Nat. Commun. 2012 3:672 doi : 10.1038/ncomms1667. 8. Gudkova D, Panasyuk G, Nemazanyy I, Zhyvoloup A, Monteil P, Filonenko V and Gout I. EDC4 interacts with and regulates the dephospho-CoA kinase activity of CoA synthase. FEBS Lett. 2012 Oct 19 ;586(20):3590-5. 9. Breus O*, Panasyuk G*, Gout IT, Filonenko V, Nemazanyy I. CoA Synthase is phosphorylated on tyrosines mammalian cells, interacts with and is dephosphorylated by Shp2PTP. Mol Cell Biochem. 2010 Feb ;335 (1-2):195-202 (*equally contributed).

Documents joints

- Site propulsé par Spip 1.9 -
-- Master de reproduction et développement - --