ObInNSC1 · The Physiological Control of Stem Cells: Obesity, Insulin, and Neural Stem Cell Dynamics

Stem cells are essential to the homeostasis, repair, and function of the tissues in which they reside. Stem cells can be regulated by systemic endocrine signals, meaning environmental factors that impact physiological state, such as diet, infection, and societal stress, can greatly impact stem cell function. Neural stem cells (NSCs) in the hippocampus divide to generate new neurons in the adult, and are known to be regulated by environmental factors.Diet-induced obesity is a modern epidemic, leading to hyperinsulinemia and diabetes. Obesity has been linked to poor performance in cognitive tests involving memory, and depression. Adult hippocampal neurogenesis is required for the proper formation of memories and learning, and has also been linked to depression. It has been suggested that a high-fat diet, and resulting obesity, impairs hippocampal neurogenesis. However, it remains unclear exactly how obesity affects adult NSCs.We will use inducible Cre recombinase genetic technologies, and advanced microscopy and image analysis, to elucidate the effects of obesity on hippocampal neurogenesis in a mouse model, with single NSC resolution. As obesity is known to alter insulin/insulin like growth factor(IGF) signalling in a variety of ways, we will elucidate the function of this pathway at the single NSC level with unsurpassable resolution in space and time, and investigate the interplay between obesity, insulin/IGF, and NSC dynamics.This project keeps a researcher with a history of research excellence in Europe, and facilitates their mobility to a distinct World-class research environment. The project utilises state-of-the-art techniques to generate new insights into the regulation of stem cells, with great potential health and economic benefits, thus helping to secure the excellence and competitiveness of Europe. Further, this project allows the researcher to gain the skills necessary to become an independent research leader.