MPhil/PhD Studentship: Synuclein plasticity: the Achilles heel of nerve function linked to the onset of Parkinson’s disease, Biosciences

University of Exeter - College of Life and Environmental Sciences

The University of Exeter is a member of the prestigious Russell Group of research-intensive universities.  We combine world-class teaching with world-class research, and have achieved a Gold rating in the Teaching Excellence Framework Award 2017. The University of Exeter has over 22,000 students and 4600 staff from 180 different countries and has been rated the WhatUni2017 International Student Choice. Our research focuses on some of the most fundamental issues facing humankind today, with 98% of our research rated as being of international quality in the 2014 Research Excellence Framework.

Academic Supervisors:

  • Dr JJ Phillips, Living Systems Institute, University of Exeter
  • Dr Daniel Kattnig, Living Systems Institute, University of Exeter
  • Dr Nicholas Harmer, Biosciences, University of Exeter

Project Description:

Parkinson’s disease (PD) is a neurodegenerative condition that stems from the progressive destruction of nerve cells in the brain that are responsible for controlling various motor functions. This results in often severe and debilitating symptoms that characterise the disease, such as shaking and convulsions. It is a progressive, age-related disorder, which means that as we continue to live healthier and longer lives, the likelihood of being diagnosed with PD increases. 1 in 500 people worldwide are diagnosed each year.

There are inherited genetic mutations that increase the risk for Parkinson’s disease. Even in these cases, there is a stochastic nature to the onset of PD at any given age. This fits with the interpretation that there is a random process at the molecular level that initiates neuronal toxicity. The protein alpha-Synuclein (aSN) is strongly implicated in PD pathogenesis. aSN is a highly dynamic molecule that adopts many postures and this structural plasticity is thought to be important for natural function. However, this also provides a potential mechanism for pathogenesis that we want to determine. Our research has recently shown that we can analyse this behaviour and measure the postures adopted by aSN molecules. To achieve this, we develop approaches using hydrogen/deuterium-exchange mass spectrometry to observe protein motion at high resolution. [1,2] This studentship provides an exciting opportunity to study the structure and dynamics of aSN protein relating to both its natural function and to Parkinson’s disease pathogenesis.

[1] Edgeworth, M. J.; Phillips, J. J.; Lowe, D. C.; Kippen, A. D.; Higazi, D. R.; Scrivens, J. H. Angew. Chem. Int. Ed. Engl. 2015, 54 (50), 15156–15159.

[2] Phillips, J. J.; Buchanan, A.; Andrews, J.; Chodorge, M.; Sridharan, S.; Mitchell, L.; Burmeister, N.; Kippen, A. D.; Vaughan, T. J.; Higazi, D. R.; Lowe, D. Anal. Chem. 2017, 89 (4), 2361–2368.

This award provides annual funding to cover tuition fees and a tax-free stipend of at least £14,553 per year. The studentship will be awarded on the basis of merit for 3.5 years of full-time study to commence as soon as possible.

Entry requirements:

Applicants for this studentship 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. 

If English is not your first language you will need to have achieved at least 6.5 in IELTS and no less than 6.0 in any section by the start of the project.  Alternative tests may be acceptable (see http://www.exeter.ac.uk/postgraduate/apply/english/).

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Type / Role:

PhD

Location(s):

South West England