G protein-coupled receptors (GPCRs), due to their cell surface expression, their tissue-selective distribution and role in amplifying signalling events make them excellent pharmacological targets, hence over 30% of current approved drugs target GPCRs (1). Variants of GPR75, an orphan GPCR whose endogenous ligand is still unknown, have recently been associated with increased body mass index and diabetes and has thereby become of significant interest to the pharmaceutical industry (2): we have also observed that mice lacking GPR75 are protected from high-fat diet induced obesity. Together these data indicate GPR75 to be novel drug target for metabolic syndrome, however, little is known about its pharmacology and downstream signalling. We have already generated several important research tools to aid in dissecting the pharmacology of GPR75, including a ligand screen based on its constitutive activity.
The overall aim of this 1-year MSc by Research (MRes) project is to elucidate the pharmacology of GPR75 in order to validate its utility as a drug target for metabolic syndrome. The MRes project will dissect the cell (hypothalamic cells, adipocytes and hepatocytes) specific G protein-coupling of GPR75 using second messenger assays and examine its physiological role by over-expressing or silencing the receptor. BRET based assays, which measure GPR75-G protein complexes, will be used to screen GPR75-ligands, including novel peptides. These parallel experimental approaches will provide an optimal lab-based training environment, experience in target validation, drug screening and molecular pharmacology and essential skills for a PhD. Understanding the pharmacology of GPR75 will help unlock the “druggability” of this exciting new target for metabolic syndrome.
CANDIDATE BACKGROUND:
The applicant should have a strong interest in pharmacology and drug discovery and hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant discipline.
We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.
Please contact Dr Fiona Murray ([Email Address Removed]) for further information.
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APPLICATION PROCEDURE:
PLEASE NOTE: International applicants are welcome to apply for this project, but will be required to self-fund the difference between home and international fees (~£20,000), and have the means to support themselves financially in the UK.
- Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
- You should apply for Medical Sciences (MSc) to ensure your application is passed to the correct team
- Please clearly note the name of the supervisor and the project title on the application form. If this is not included, your application will not be considered for the project.
- Candidates should have (or expect to achieve) a minimum of a 2:1 Honours degree at undergraduate level.
- Your application must include: a personal statement, an up-to-date copy of your academic CV, and clear copies of your educational certificates and transcripts.
- If you are still undertaking your undergraduate degree it is helpful to the selectors if you could provide documentation showing your grades to date (this can be a screenshot from an online portal).
- Please DO NOT provide a research proposal with this application.
- Please note: Project supervisors will not respond to requests for funding assistance.
- If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at [Email Address Removed]
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