In the Panasyuk Lab we want to know: How do cells sense the lack of nutrients in their environment? This is fundamental to better understand how cellular metabolic activities are coordinated, how gene transcription is orchestrated, and how their defects are implicated in human diseases (www.panasyuklab.fr). To address these questions, we focus on still largely enigmatic phosphatidylinositol 3-kinase (PI3K) signalling, that emerged in evolution as a central signalling hub for effective use of metabolic fuel. Class 3 PI3K is the only member of the PI3K family active in all eukaryotes to generate PI3P, a membrane-born messenger critical at multiple steps for vesicular trafficking. These include essential cellular processes such as lysosomal degradation by autophagy, endocytosis, and ER-Golgi sorting. We discovered that class 3 PI3K is essential for life and is indispensable to maintain whole-body metabolic homeostasis (1,2). We also demonstrated that class 3 PI3K has an unappreciated role in the transcriptional control of mitochondrial biogenesis and lipid catabolism in fasting (3,4). In our most recent work, we found that both subunits of class 3 PI3K interact with RNA Pol2, co-localize with active transcription sites and can co-activate the circadian clock transcription factor complex of Bmal1-Clock. In physiology, we demonstrated that class 3 PI3K is required for metabolic rhythmicity in liver and, unexpectedly, it promotes pro-anabolic de novo purine nucleotide synthesis (5). Our unpublished findings show that chromatin recruitment of class 3 PI3K subunits is controlled by fasting-feeding and that class 3 PI3K is essential for global transcriptional rewiring in metabolic adaptation to fasting. During seminar these published and unpublished findings will be discussed. 

1. Nemazanyy I, et al., Nat. Comm. 2015; 6:8283

2. Nemazanyy I, et al., EMBO Mol Med. 2013; 5(6):870-90

3. Shibayama Y, et al. Acta Physiol (Oxf) 2022;e13793. doi: 10.1111/apha.13793.

4. Iershov A, et al. Nat Commun. 2019, Apr 5;10(1):1566.

5. Alkhoury, C., Henneman, N.F., et al. Nat Cell Biol 25, 975–988 (2023).

 

Ganna Panasyuk is a principal investigator at Institute Necker Enfants Malades (INEM, INSERM Unit 1151, Paris, France). She has earned her PhD degree in Molecular Biology from the Institute of Molecular biology and Genetics in Kyiv, Ukraine. Early on in her training she has got interested in transduction mechanisms governing growth control such as mTOR/PI3K signalling pathway. She was trained in this field as a postdoc, first, in the lab of Ivan Gout at University College London, UK, and then in the lab of Mario Pende at INSERM, Paris, France. Since 2013 she holds a tenure track position at INSERM and in 2019 was awarded research director position to lead the research program at INEM institute. Today, her team aims to elucidate molecular mechanisms of nutrient sensing for metabolic control and its implication in human disease.

To learn more about Ganna Panasyuk team go to: http://www.panasyuklab.fr

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