PhD Studentship: Investigating How Accessory Proteins Modify The Function of G Protein-coupled Receptors (GPCRs) Involved In Appetite Regulation

This PhD project will explore how accessory proteins modify the signalling of GPCRs involved in appetite regulation, using state-of-the-art signalling assays and cutting-edge microscopy techniques. G protein-coupled receptors (GPCRs) are membrane proteins that have a critical role in energy homeostasis, contributing to food intake, energy expenditure and glycaemic control. Genetic mutations in GPCRs cause obesity and blockbuster obesity drugs target GPCRs. Interactions between GPCRs and accessory proteins can facilitate GPCR signalling but the molecular mechanisms involved are poorly understood.

This project will explore how accessory proteins interact with GPCRs to modify signalling and trafficking. The student will investigate protein interactions between accessory proteins and GPCRs and their binding kinetics using fluorescence correlation spectroscopy. The effects of accessory proteins on GPCR signalling will be explored using a variety of assays including BRET and cAMP Glosensor, while receptor internalisation will be assessed using structured illumination microscopy. There will also be the opportunity to learn generic skills including cell culture and molecular biology techniques (e.g. cloning). 

The candidate will be based primarily at the University of Birmingham but will undertake research visits to the University of Nottingham to learn fluorescence correlation spectroscopy techniques. This project provides an exceptional opportunity to engage in multidisciplinary research with access to state-of-the-art facilities at two leading universities. This research will advance our understanding of the fundamental mechanisms by which GPCRs regulate food intake and has the potential to lead to novel therapeutics to treat metabolic disease.

Full project description here: https://warwick.ac.uk/fac/cross_fac/mibtp/phd/supervisors/cgorvin/

Please reach out to Dr Gorvin for an informal discussion prior to applying.
Full eligibility criteria and instructions on how to apply can be found here: https://warwick.ac.uk/fac/cross_fac/mibtp/phd/application/

Information on the MIBTP DTP programme - https://warwick.ac.uk/fac/cross_fac/mibtp/ Birmingham
MIBTP page - https://www.birmingham.ac.uk/research/activity/mibtp 

References:

1. Jamaluddin, A., Wyatt, R.A., Lee, J., Dowsett, G.K.C., Tadross, J.A., Broichhagen, J., Yeo, G.S.H., Levitz, J., and Gorvin, C.M. (2024). TheMRAP2 accessoryprotein directly interacts with melanocortin-3 receptor to enhance signaling. bioRxiv, 2024.2011.2006.622243. 10.1101/2024.11.06.622243.
2. Wyatt, R.A., Jamaluddin, A., Mistry, V., Quinn, C., and Gorvin, C.M. (2024). Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways. bioRxiv, 2024.2011.2019.622403. 10.1101/2024.11.19.622403.
3. Goulding, J., Kondrashov, A., Mistry, S.J., Melarangi, T., Vo, N.T.N., Hoang, D.M., White, C.W., Denning, C., Briddon, S.J., and Hill, S.J. (2021). Theuse of fluorescence correlation spectroscopy to monitor cell surface beta2-adrenoceptors at low expression levels in human embryonic stem cell-derived cardiomyocytes and fibroblasts. FASEB J 35, e21398. 10.1096/fj.202002268R.
4. Jamaluddin, A., and Gorvin, C.M. (2023). RISING STARS: Targeting Gprotein-coupledreceptors to regulate energy homeostasis. J Mol Endocrinol 70. 10.1530/JME-23-0014.
5. Gorvin, C.M., Rogers, A., Hastoy, B., Tarasov, A.I., Frost, M., Sposini, S., Inoue, A., Whyte, M.P., Rorsman, P., Hanyaloglu, A.C., et al. (2018). AP2sigma Mutations Impair Calcium-Sensing Receptor Trafficking and Signaling, and Show an Endosomal Pathway to Spatially Direct G-Protein Selectivity. Cell Rep 22, 1054-1066. 10.1016/j.celrep.2017.12.089.

Funding Details

Additional Funding Information

This is a BBSRC funded PhD studentship and is part of the Midlands Integrative Biosciences Training Partnership (MIBTP) DTP. The MIBTP studentship offer a comprehensive support package, including fees (the cost of the UK fee rate), a tax-free annual stipend, a travel and conference budget, a generous consumables budget, and the use of a MacBook Pro for the duration of the programme.

Home (UK), EU or International candidates are eligible to apply –up to 30% of the awards can be made to international candidates.

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