This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP). The DTP offers an interdisciplinary research training programme delivered by a consortium comprising the Universities of Bath, Bristol and Exeter, Cardiff University and Rothamsted Research, alongside six regional associate partners: Marine Biological Association, Plymouth Marine Laboratory, Swansea University, UCB Pharma, University of the West of England and SETsquared Bristol. The partnership has a strong track record in advancing knowledge through high quality research and teaching, in collaboration with industry and government. For more information about the DTP, see https://www.swbio.ac.uk/
Studentships are available for entry in September/October 2020.
All SWBio DTP projects will follow a structured 4-year PhD model, combining traditional project-focussed studies with a taught first year which includes directed rotation projects.
Overview of this PhD project:
Prof Jody Mason, Department of Biology & Biochemistry (University of Bath) https://researchportal.bath.ac.uk/en/persons/jody-mason
Dr Robert Williams (University of Bath) https://researchportal.bath.ac.uk/en/persons/robert-williams
Dr Richard Sessions (University of Bristol) https://research-information.bristol.ac.uk/en/persons/richard-b-sessions(e6ebec41-c3f0-4f5d-abf5-6bf8bc2c7e89).html
The student 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 (Cheruvara et al, J.Biol.Chem 2015). Using a novel screening system that targets the natural state of aS, that is prior to misfolding and aggregation, the student will screen large peptide libraries (>2 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 student 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 computational 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.
Applicants must 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.
How to apply:
Applications should be submitted on the University of Bath’s online application form for a PhD in Biosciences: https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-DT01&code2=0004
Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section. You may apply for more than one project if you wish but you should submit a separate personal statement relevant to each one.
More information about applying for a PhD at Bath may be found on our website: https://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/