Dr Caroline Gorvin, who is based within the Institute of Metabolism and Systems Research, has been awarded the highly distinguished Sir Henry Dale Fellowship worth nearly £1 million to better understand how food intake is regulated, which could lead to improvements in treatment for chronic conditions such as obesity and under-nutrition.
Obesity currently affects 13% of the worldwide population, and is a major risk factor for type-2 diabetes, cardiovascular disease, cancer and severe COVID-19 illness. Conversely, under-nutrition is increasingly prevalent in ageing populations, associated with frailty, increased fractures and prolonged hospital stays. By understanding fundamental cell mechanisms involved in appetite regulation, Dr Gorvin’s research group aims to ultimately design better drugs, with fewer side effects, to regulate food intake that could prevent obesity and under-nutrition.
Funded by the Wellcome Trust and The Royal Society, this highly competitive five year award will investigate how appetite is regulated in the brain by the hormone ghrelin. Ghrelin is produced by the stomach and tells the brain when to eat and store fat. Ghrelin does this by binding to the growth hormone secretagogue receptor-1a (GHSR1a) on brain cell surfaces. GHSR1a is a G-protein-coupled receptor (GPCR), so-called because it associates with G-proteins that initiate message relays (signalling), to decide cell responses. GHSR1a seems an ideal drug target for manipulating hunger, but GHSR1a inhibitors are ineffective. This could be because signalling by GHSR1a is more complex than previously thought.
In this fellowship Dr Gorvin will investigate how GHSR1a may achieve this complexity. She will assess: how GHSR1a clusters with other GPCRs in brain tissue; how interacting proteins influence GHSR1a signalling and movement around cells (trafficking); and whether activating other GPCRs influences ghrelin-mediated physiological functions. Dr Gorvin’s research group will use advanced microscopy available in the Centre of Membrane Proteins & Receptors (COMPARE) and state-of-the-art signalling assays to achieve these aims.
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For this research, Dr Gorvin will collaborate with Associate Professor Joshua Levitz and his research group at Weill-Cornell Medicine. She will also collaborate with and Professor Lora Heisler’s research group at the University of Aberdeen.