Team Panasyuk is looking for enthusiastic and ready-to-learn, scientifically driven trainees with a strong interest in signal transduction mechanisms and not shy of taking on challenging chronobiology, cell biology and metabolism projects.
We propose two ambitious and innovative MSc projects for 2020-2021 academic year.
Our team addresses these fundamental questions: How are cellular metabolic activities controlled by nutrient sensing signal transduction pathways? And how defects in these molecular mechanisms could be explored to understand and to treat human diseases? We focus on an essential nutrient sensing signal transduction pathway present in all eukaryotic cells, the Vps15/Vps34 complex (Vacuolar Protein Sorting 15/34, known as class 3 PI3K). Our team has shown that class 3 PI3K is required to maintain whole body metabolic homeostasis, and recently demonstrated its essential function in transcriptional control of lipid metabolism (Nemazanyy et al, EMBO Mol Med, 2013; Nemazanyy et al, Nature Comm, 2015; Iershov et al, Nature Comm, 2019).
Project 1: Nuclear phosphatidyl inositol signaling in metabolic control
Generation of a signaling lipid a phosphatidylinositol 3-phosphate (PI3P) is the best-known function of class 3 PI3K. PI3P’s functions have been thoroughly characterized in the cytosol in the membrane vesicular trafficking events of autophagy and endocytosis. Surprisingly, early reports on PI3P subcellular distribution suggest that additional pools of PI3P exist in the cell, particularly in the nucleus.
The main objectives of this M2 project are:
1) Establish nuclear production of PI3P;
2) Discover the binding partners of nuclear PI3P;
3) Determine the impact of nuclear PI3P depletion on nuclear organization and metabolic gene expression.
Project 2: Novel functions of class 3 PI3K in metabolic time-keeping
Our most recent discovery advocates that class 3 PI3K is also involved in whole-body metabolic control by functional interaction with the circadian clock mechanism in liver (Alkhoury et al, in preparation). The circadian clock is an evolutionary conserved anticipatory mechanism that functions in nearly all cells of our body. It assures metabolic adaptation to resting and active phases of the daily cycle we experience. Accordingly, different metabolic pathways have been reported to control the circadian clock molecular machinery and consequent circadian responses such as feeding behavior. The link between class 3 PI3K, circadian clock in different metabolic tissues and feeding behavior is still unexplored. To this end, the main objectives of proposed M2 project are:
1) Determine the role of class 3 PI3K in the regulation of circadian clock machinery in different metabolic organs beyond the liver;
2) Discover the molecular mechanism by which class 3 PI3K controls the circadian clock;
3) Investigate the feeding behavior of class 3 PI3K mutants in physiological and nutritional stress conditions.
If you are interested in joining us, please email the following information to: firstname.lastname@example.org
- Letter of motivation briefly explaining which project interests you and why
- Your CV
- Contact of at least one reference
We look forward to hearing from you!