Genomic and functional characterisation of cell-type specific epigenetic and genetic mechanisms implicated in human obesity.

Epigenetic switches on DNA turn nearby genes on and off without changing the underlying genetic code. These switches are implicated in many aspects of obesity and diabetes, but finding and proving which switches cause human disease is a major challenge. I have used innovative screening and refinement strategies to discover epigenetic switches in human fat cells that may contribute to obesity and diabetes, and genes these switches are likely to affect. I will investigate whether and how these genes cause obesity and diabetes by deleting each gene in a mouse model of human disease physiology. I will map the locations of the epigenetic switches to identify proteins with switch activating potential, then use DNA-editing tools to show that individual switches and proteins actively regulate their corresponding genes, all in human fat cells. With these convergent approaches, I aim to discover new mechanisms of obesity and diabetes and potential treatment targets.