SWBio DTP: How does the cellular environment affect opioid receptor signalling? University of Bath in United Kingdom

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP) .

The SWBio DTP is funded by BBSRC and involves a partnership of world-renowned universities, research institutes and industry, based mainly across the South West and Wales. This partnership has established international, national and regional scientific networks, and widely recognised research excellence and facilities.

Studentships are available for entry in September 2025.

All SWBio DTP projects will follow a structured training programme to ensure you are well equipped as a bioscience researcher, supporting careers into academia, industry and beyond.

Supervisory Team:

Lead supervisor: Dr Chris Bailey , University of Bath, Department of Life Sciences (email: [email protected] )

Co-supervisors: Dr Robin Corey , University of Bristol, School of Physiology, Pharmacology & Neuroscience,

Prof Eamonn Kelly , University of Bristol, School of Physiology, Pharmacology & Neuroscience

The Project :

G protein coupled receptors (GPCRs) are the largest family of cell surface receptors in mammals. There are >800 different GPCRs playing critical roles in a wide range of biological processes from the senses of sight, smell and taste, to the actions of many neurotransmitters and hormones.

Recently, it has become clear that individual GPCRs can signal differently depending on their environment, so-called ‘biased signalling’ [1]. This could be due to different effects of the ligand, or agonist, activating it (‘ligand bias’) or by the different cellular environment in which the GPCR resides (‘location bias’). With location bias, GPCR signalling can be affected by features that vary between membranes both between cells and within the same cell, including membrane potential [2], membrane curvature [3], the composition of the lipid membrane [4], or by the subcellular neuronal location of the receptor [5, 6].

In this project we will take a transdisciplinary approach, using a combination of in silico, in vitro, ex vivo and in vivo techniques, to help define and understand location bias of GPCR signalling. We will focus on the mu-opioid receptor (MOPr), a GPCR that is involved in nociception, mood and euphoria, and is endogenously activated by endorphins and enkephalins, as well as by opioid drugs such as morphine, heroin, and fentanyl.

Using molecular docking and atomistic/coarse-grained molecular dynamics [7, 8], we will explore how ligand-receptor binding is affected by the composition, curvature and membrane potential of the cell membrane. These findings will then be tested in vitro using mutagenesis and BRET assays to measure G-protein activation and arrestin recruitment [9].

In parallel, using brain slice electrophysiology, the functional impacts of the in silico and in vitro findings will be determined: how do different MOPr agonists signal through MOPrs at different cell types and at different subcellular regions [9, 10]? Ultimately the aim will be to use assays of nociception and euphoria [11, 12] to assess the in vivo impacts of location bias.

Keywords: Opioids, GPCRs, molecular dynamics, neuroscience, addiction

Candidate Requirements:

Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree (or international equivalent), in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have Master’s degree or have significant relevant non-academic experience.

In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification/experience* is required.

* Physics A-level (grade B and above) or units in your degree with a significant mathematical component, e.g. maths, statistics, bioinformatics.

Applicants must ensure they highlight their Maths background within their application and to upload any supporting evidence.

If English is not your first language, you will need to have achieved Academic IELTS 6.5 overall (with no less than 6.5 in any of the four skills). Find details of other acceptable tests and further information on our website.

Enquiries and Applications:

Informal enquiries are welcomed and should be directed to the lead supervisor.

Formal applications should be submitted on the University of Bath’s online application form for a PhD in Biosciences .

When completing the application form, please:

1.      In the Funding your studies section, select ‘SWBio DTP’ as the studentship for which you are applying.

2.      In the Your PhD project section, quote the project title of this project and the name of the lead supervisor in the appropriate boxes.

3.      Should you wish to apply for more than one project at Bath (up to a maximum of two projects), you may do so within the same application but you should ensure you quote each project title (and intended supervisors) in order or preference in the appropriate boxes within the Your PhD project section and, IMPORTANTLY, you should upload a separate (clearly labelled) personal statement for each one, outlining your interest and suitability for that particular project.

See our website for more information about applying for a PhD at Bath.

Equality, Diversity and Inclusion:

The aim of the SWBio DTP is to support students from a range of backgrounds and circumstances. Where needed, we will work with you to take into consideration reasonable project adaptations (for example to support caring responsibilities, disabilities, other significant personal circumstances) as well as flexible working and part-time study requests, to enable greater access to a PhD.  All our supervisors support us with this aim, so please feel comfortable in discussing further with the listed PhD project supervisor to see what is feasible.

If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.