Post doctoral position to identify mTOR amino-acid sensing regulators in rainbow trout
UMR1419 INRA-UPPA NuMeA, Saint Pée-sur-Nivelle, France
Application deadline: 01st of April 2018
Starting date: September 2018
Funding: E2S junior chair project from the university of “Pau et des Pays de l’Adour” UPPA
Duration: 3 years (with possible extension for up to 2 additional years)
Gross salary: 34 k€ / year
Scientific background / Project:
The discovery of the serine/threonine kinase called mechanistic Target of Rapamycin (mTOR) considerably contributed to improve our understandings in basic cell/organism biology. More than 20 years later, it is generally accepted that mTOR plays a central role linking nutrients availability with cell growth proliferation and metabolism. Amongst the multitude of signals leading to mTOR activation, one remains to be clarified: the amino-acid sensing pathway. Indeed, numerous studies performed in various in vitro and in vivo models (human and mouse cell lines, yeast…) have identified key players and pathways by which mTOR senses amino acids. However, the available data are still contradictory and far from exhaustive.
In this context, the NuMeA (Nutrition Metabolism Aquaculture) INRA-UPPA join unit has been conducting research for the past ten years on the role of amino acids in the control of the mTOR signalling pathway in rainbow trout (Oncorhynchus mykiss), a strict carnivorous species metabolically adapted for high utilization of dietary amino acids. Research carried out in this unit has thus led to the characterization of the main actors and signalling pathways involved in the control of mTOR in this species (1-9) and the postdoctoral position proposed here is part of work performed by the unit on the role of amino acids in the control of mTOR.
Based on previous studies and preliminary results, our current working hypothesis is that mTOR is less efficiently activated by amino acids in rainbow trout compared to mammals. We now aim to understand, at the molecular level, reasons that impair mTOR amino acid sensing in trout. The expression balance between mTOR activators and repressors as well as the identification of specific mTOR repressors in trout represents few examples of experiments that the candidate will be encouraged to explore to better characterise mTOR amino acid sensing in trout. Directed strategies (such as siRNA and CRISPR/Cas9 genome editing technology) combined to a high-through put screen based on a downstream pathway regulated by mTOR will be employed to successfully address this ambitious project. Once the candidate will have identified and studied key genes involved in mTOR amino acid sensing machinery in fish cell lines, the project will then be up-scaled by in vivo experiments to determine the outcomes of the dysregulation of the newly identified genes on trout physiology, metabolism and growth.
The successful candidate will work in a young and dynamic group in close collaborations with local, national and international talented scientists. He/she will also be given the opportunity to be involved in the teaching program of the University of Pau for a total of 64 hours per years.
Key words: mTOR, amino acid metabolism, autophagy, growth factor, fish, aquaculture
Applicant‘s profile: The candidate must be highly motivated with a PhD in biochemistry or cellular biology and a good scientific track record. A strong experience in molecular and cell biology techniques is desired and a previous experience in high-through put screen would be an advantage. The candidate must be fluent in English with the capacity to work autonomously besides developing strong collaborations. Application will include (in a single pdf file): – A motivation letter – A curriculum vitae – A short summary of your past research (2 pages maximum) – Contact details of three referees Application must be send to the following email address with the title “Post-doctoral application”: PhD.Postdoc.E2S.NuMeA@gmail.com. For more details, please visite our website: https://www6.bordeaux-aquitaine.inra.fr/st_pee_eng/UR-NuMeA. Feel free to contact us using the same email address with the title “Informations”.
1. I. Seiliez et al., An in vivo and in vitro assessment of TOR signaling cascade in rainbow trout (Oncorhynchus mykiss). Am J Physiol Regul Integr Comp Physiol 295, 23 (2008).
2. I. Seiliez et al., Feeding status regulates the polyubiquitination step of the ubiquitinproteasome-dependent proteolysis in rainbow trout (Oncorhynchus mykiss) muscle. J Nutr 138, 487 (2008).
3. M. Lansard, S. Panserat, E. Plagnes-Juan, I. Seiliez, S. Skiba-Cassy, Integration of insulin and amino acid signals that regulate hepatic metabolism-related gene expression in rainbow trout: role of TOR. Amino Acids 39, 801 (Aug, 2010).
4. I. Seiliez et al., Dietary carbohydrate-to-protein ratio affects TOR signaling and metabolismrelated gene expression in the liver and muscle of rainbow trout after a single meal. Am J Physiol Regul Integr Comp Physiol 300, 5 (2011).
5. M. Lansard et al., L-leucine, L-methionine, and L-lysine are involved in the regulation of intermediary metabolism-related gene expression in rainbow trout hepatocytes. J Nutr 141, 75 (2011).
6. I. Seiliez et al., Amino acids downregulate the expression of several autophagy-related genes in rainbow trout myoblasts. Autophagy 8, 364 (Mar, 2012).
7. W. Dai et al., Post-prandial regulation of hepatic glucokinase and lipogenesis requires the activation of TORC1 signalling in rainbow trout (Oncorhynchus mykiss). J Exp Biol 216, 4483 (2013).
8. W. Dai, S. Panserat, F. Terrier, I. Seiliez, S. Skiba-Cassy, Acute rapamycin treatment improved glucose tolerance through inhibition of hepatic gluconeogenesis in rainbow trout (Oncorhynchus mykiss). Am J Physiol Regul Integr Comp Physiol 307, 27 (2014).Tweet