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-renown universities, research institutes and industry across the South West and Wales. This partnership represents a distinctive group of bioscientists with established international, national and regional networks and widely recognised research excellence. We aim to provide students with outstanding interdisciplinary research training.
Studentships are available for entry in October 2023.
All SWBio DTP projects will follow a structured 4-year PhD programme, combining traditional project-focussed studies with a taught first year which includes directed rotation projects.
Supervisory Team:
Lead supervisor: Prof Stephen Husbands, University of Bath, Department of Life Sciences ([Email Address Removed]).
Co-supervisors: Prof Emma Robinson (University of Bristol), Dr Chris Bailey (University of Bath) and Prof David Heal (DevelRx, subject to contract)
CASE Partner (subject to contract):
DevelRx Limited (Nottingham)
The Project:
Mu opioid agonists are powerful analgesics, but their clinical value is limited by pharmacological tolerance, respiratory depression and abuse potential. There are three main subtypes of opioid receptors and evidence that different subtypes can combine to form heterodimers with their own unique functional profile. One area of particular interest is how these different receptor subtypes and heterodimers modulate euphoria versus dysphoria. The euphoric effects of mu-opioid agonists are well known. In contrast, kappa-opioid agonists are analgesic but dysphoric and in mixed mu/kappa agonists may attenuate potential for abuse. Moreover, kappa-receptor antagonists are showing potential as antidepressants. By better understanding the psychopharmacology of the mu- versus kappa-opioids and their heterodimers, there is the potential to develop novel treatments for chronic pain which lack the abuse potential of traditional opioids such as morphine. There is also growing interest in novel opioid ligands as treatments for major depression.
The aim of this project is to explore the effects of mu and kappa opioid receptors using rodent models of depression, abuse liability and reward processing. The project will also explore the chemistry of novel opioid ligands including those with activity at both mu and kappa receptors and those that are heterodimer agonists. The in vivo studies will utilise both reference compounds and novel drugs developed as part of the PhD. We have several novel compounds available which have yet to be studied in the context of these functional roles. We will also test NNTA, a novel mu/kappa heterodimer agonist. The behavioural studies will focus on two key domains, affect and abuse liability and will use translational rodent models. The project also benefits from a collaboration with the industrial partner, DevelRx (subject to contract). DevelRx has world-leading knowledge and expertise in evaluating the abuse potential of novel drugs including a wide variety of opioid receptor ligands including Blue-181, samidorphan, naloxegol (Movantik®) and difelikefalin (Korsuva®). Placements at DevelRx will provide the student with training in (i) pharmaceutical R&D strategies for developing novel CNS drugs including those with intrinsic potential for abuse, (ii) design of Safety Pharmacology experiments to assess the abuse and dependence potential of CNS drugs for medical use, and (iii) the regulatory framework and preparation of documentary evidence on efficacy and safety to support drug approval.
The project has the potential to be undertaken on a part-time basis depending on the specific working pattern required; however, some of the behavioural studies will require periods where daily testing of the animals is necessary. Note for international applicants: due to complexities and restrictions associated with visas for part-time studies, we are currently unable to accept part-time international students to the programme.
The project will be based at both the University of Bath and the University of Bristol with placement/s at DevelRx (subject to contract).
Requirements:
Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree (or the equivalent), in an appropriate subject. Applicants with a Lower Second Class degree will be considered if they also have Masters degree or significant relevant non-academic experience.
Also, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in SWBio 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 (Biology & Biochemistry). Note: if you are successful, you will be transferred to the PhD in Pharmacy & Pharmacology (SWBio DTP) programme at the point of offer.
When completing the form, please identify your application as being for the SWBio DTP studentship competition in Section 3 Finance (question 2) and quote the project title and lead supervisor’s name in the ‘Your research interests’ section. You may apply for more than one project within the same application but 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:
We want to support diverse and inclusive work environments. We therefore welcome applications from individuals regardless of their race, ethnicity, sexual orientation, religion, age, gender or disability status.
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.
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