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Understanding how GPCRs integrate nutritional and hormonal signals at the hypothalamic arcuate nucleus

Project Description

Obesity is a global healthcare problem predicted to affect half the worldwide population by 2030, and is a risk factor for diabetes and cardiovascular disease. Conversely, malnutrition and cachexia are increasingly prevalent in an ageing population. Hypothalamic arcuate neurons play a critical role in integrating signals from peripheral tissues to regulate feeding and energy expenditure. G-protein-coupled receptors (GPCRs) are highly expressed at arcuate neurons and mediate responses to many of these nutritional and hormonal cues. However, there is a limited repertoire of GPCR signalling pathways, and many receptors are expressed on the same neurons. Consequently, how GPCRs integrate stimulatory cues to regulate appetite is poorly understood. Using a multidisciplinary approach including molecular, computational, biophysical and state-of-the-art imaging techniques, this studentship aims to interrogate the signalling and trafficking of hypothalamic GPCRs to discover how they interact and how this could be manipulated to regulate food intake.

The student will learn a variety of techniques to examine GPCR function including cell culture, molecular biology, structural modelling, biophysical techniques, signalling assays (FRET, BRET, HTRF) and single-molecule (super-resolution) microscopy. They will benefit from an interdisciplinary supervisory team comprising: Dr Caroline Gorvin, the principal supervisor based at the Institute of Metabolism and Systems Research, University of Birmingham; Professor Dmitry Veprintsev, University of Nottingham; and Professor Davide Calebiro, University of Birmingham. The student will be expected to embrace being part of a world-class metabolic research institute within IMSR and an innovative interdisciplinary environment in the Centre of Membrane Proteins and Receptors (COMPARE).

Person Specification
Applicants should have a strong background in cell biology or pharmacology and an interest in membrane proteins, GPCRs and advanced imaging techniques. They should hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a related biological subject (e.g. molecular biology, biochemistry, biomedical sciences).

Funding Notes

Please check the MRC website for full eligibility criteria View Website

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