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Decoding genomic signatures of metabolic reprogramming in diabetes and obesity

EpiCrossBorders: International Helmholtz-Edinburgh Research School for Epigenetics

Prof N. H. Uhlenhaut , Prof C Ponting , Dr Fabiana Quagliarini Friday, December 04, 2020 Competition Funded PhD Project (Students Worldwide)

About the Project

This project is part of the international call of EpiCrossBorders: Helmholtz-Edinburgh International Research School for Epigenetics

Project description:
Excess of food intake is the leading cause of metabolic disease. Over-nutrition alters those metabolic programs required to maintain energy balance, by affecting nutrient and hormonal signaling. Crucial to this adaptation is the remodeling of target gene expression. The transcriptional control of metabolic homeostasis is primarily mediated by Nuclear Receptors (NR), a group of transcription factors that act as genomic switches, by directly responding to dietary lipids, hormones, and other intracellular signals. Once activated, NR bind to promoter and enhancer regions, recruit coregulator complexes, and regulate gene expression through mechanisms that largely depend on the epigenome editing. Hence, these transcriptional complexes function as metabolic sensors, capable of inducing histone modifications that dynamically reorganize the chromatin landscape depending on the environmental conditions. In our group we aim to elucidate the molecular mechanisms by which nutritional status influences NR genomic actions via the identification of specific genomic signatures and transcriptional profiles. The project will use interdisciplinary approaches including Next Generation Sequencing techniques (ChIP-seq, RNA-seq, ATACseq), mouse model of metabolic diseases, human genetics, and computational biology, in order to understand how the nutritional challenge and altered chromatin landscape affect the metabolic homeostasis. Upon completion, we will be able to address novel mechanisms of target gene regulation during the hepatic adaptation to over-nutrition, which could be ultimately exploited in the field of pharmacological research.

Applications for this project have to go through the call of EpiCrossBorders: International Helmholtz-Edinburgh Research School for Epigenetics.
For more information about our program and to apply please visit our website: https://www.helmholtzresearchschool-epigenetics.org/
For enquiries please contact the Research School Office at

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