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Unravelling the Cause of Parkinson’s Disease in Molecular Detail

Project Description

Prof. Matthew Crump (School of Chemistry, University of Bristol)
Dr Richard Taylor (UCB, Slough, UK)
Prof. Jody Mason (Department of Biology and Biochemistry, University of Bath)

A CASE award PhD project is available for commencement in September 2020 as one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (BBSRC SWBio DTP). The SWBio DTP projects are designed to provide outstanding interdisciplinary training in a range of topics in Agriculture & Food Security and world-class Bioscience, underpinned by training in mathematics and complexity science. Each project will be supervised by an interdisciplinary team of academic staff and will follow a structured training 4-year PhD model. This program offers a tailored PhD experience with research rotations, lectures courses and a placement period within UCB. You will be part of a cohort of 20+ fellow students and the complete package makes an excellent training experience.

Project Description. Parkinson’s disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer’s, affecting millions of people globally. Rapid decline in cognitive function is accompanied by progressive loss of motor function resulting in increasing disability and ultimately death. Currently there is no cure for PD.

Autopsy of PD brains reveals extensive tangled deposits, known as Lewy bodies and Lewy neurites which have accumulated in the neurons, resulting is cell death. These deposits are the hallmark of PD and are comprised of twisted fibrils consisting of a protein known as a-Synuclein. This protein has a natural physiological function but under certain conditions can misbehave and form aggregates. There is also strong genetic evidence linking a-Synuclein to PD, consequently this protein has become the subject of intensive research in efforts to find a cure. Whilst its true physiological function in the brain is unknown, it is clear that a-Synuclein is able to bind to cell membrane surfaces comprising phospholipids and may be involved in intercellular signalling. As a result, recent biophysical investigations have concentrated on the elusive mechanisms of membrane association, the early stages of oligomer formation and the changes in protein shape that accompany these processes.

In this project we seek to address these challenges and apply advanced spectroscopic (NMR) and biophysical techniques to a series of a-Synuclein molecules engineered specifically to provide information at the molecular level regarding the assembly of single molecules into aggregated species on the surface of homogeneous particles. Using a combination of protein biochemistry and chemical biology approaches we will reveal the precise molecular geometry and alignment of a-Synuclein molecules in the toxic oligomeric species providing new insight on potential axes of therapeutic intervention.

The studentship will primarily benefit from access to UCB’s extensive Structural Biology infrastructure, including NMR facilities, via the industrial placement component of the project. This project will also be undertaken in collaboration with the Department of Biology and Biochemistry (Bath, Jody Mason) who will bring expertise in the design and analysis of peptides to bind, reverse and block protein-protein interactions relevant to human health.

Closing date for applications is 02/12/2019. For informal enquiries please contact

Funding Notes

The studentship will provide funding for a stipend (currently £15,009 pa for 2019-20), a salary enhancement provided by UCB, research costs and UK/EU tuition fees at Research Council UK rates for 4 years for full-time students, pro-rata for part-time students. The SWBio DTP is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bristol (lead), Bath, Cardiff, Exeter, Rothamsted Research and associate partners. More information on this scheme can be found View Website. Appointment is by competitive interview and the closing date for online applications at the above SWBio website is Monday 2nd December.


Keywords Parkinson's CASE NMR Pharmaceuticals Pharma

How good is research at University of Bristol in Chemistry?

FTE Category A staff submitted: 58.60

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