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 Jody Mason, University of Bath, Department of Life Sciences (email: [Email Address Removed])
Co-supervisors: Prof Matthew Crump (University of Bristol) and Dr Robert Williams (University of Bath)
The Project:
The successful candidate will develop peptides that can be used to effectively block formation of a toxic protein responsible for the pathology of Parkinson's disease (PD). The protein, known as alpha-synuclein (aS), self-associates inside dopamine producing cells in the brain to form toxic clumps known as Lewy bodies that interfere with normal brain function, leading to the symptoms of the disease. We will inhibit this process building from a system that we have demonstrated to work (Meade et al J Mol Biol 2021, 2022, Watt et al ACS Chem Neurosci 2022, Watt et al J Biol Chem 2022). Using a novel screening system that targets the natural folded state of aS, that is prior to misfolding and aggregation, the student will screen large peptide libraries (>20 Million members) inside living bacterial cells. In this assay, inhibitors are only selected if the very first step in aggregation is blocked, leading to a restoration of cell viability.
The successful candidate will use the screening assay to generate numerous inhibitory peptides to block the very first steps in the misfolding of aS. This will provide a wide range of sequences from which we can understand the mechanism of inhibition via biophysical, neuronal cell-based, and structural biology methods. Our overarching aim is to assign function to specific sequence elements within our newly generated inhibitors to demonstrate the principles of rational inhibitor design, ultimately improving the properties of future peptide generations. Finally, by comparing endogenously produced to externally added peptides, the student will begin to explore aspects of drug delivery, such as permeability to reach intracellular targets.
The composition of the supervisory team ensures comprehensive expertise in all facets of this interdisciplinary project. The training environment will be highly supportive and stimulating, including ample opportunity for wider engagement with the scientific community. You will be guided through the challenges and rewards of this project while gaining a wide range of skills that are translatable to many other systems.
Project keywords: constrained proteins, Parkinson’s disease, protein-protein interactions, peptide inhibitor, drug development.
Requirements:
Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have Masters 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 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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