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Investigation of the relationship between LRRK2 and α-synuclein in Parkinson’s disease.


Project Description

Supervisor(s):
Kurt De Vos (SITraN, Sheffield), Heather Mortiboys (SITraN, Sheffield), Laura Volpicelli- Daly (UAB, Alabama)

Project details:
Applications are being invited for a four-year Basic Science PhD Studentship, starting in October 2019.

This PhD studentship is part of the Battelle – Jeff Wadsworth Scholarship Programme based at the University of Sheffield; funded by a generous donation to the University by the Battelle Memorial Institute based in the USA. The ambition for the scholarship programme is to provide an outstanding educational experience for early-career researchers by fostering a global community of scholarship to support the exchange of new ideas and the importance of working with others to solve problems.

The successful candidate will join an established training programme at the Sheffield Institute for Translational neuroscience (SITraN) in the laboratory of Dr Kurt De Vos. This studentship includes a 3-6-month research placement in the laboratory of Dr Laura Volpicelli at the University of Alabama at Birmingham, USA.

Parkinson’s disease (PD) is characterised by α-synuclein pathology. On the one hand, α- synuclein is the main component found in intraneuronal inclusion bodies called Lewy bodies that are the hallmark pathology of most PD cases. On the other hand, recent work has shown that neuron-to-neuron transfer of pathogenic fibrillar α-synuclein aggregates is a key phenomenon in the spread of PD pathology through the brain of affected patients. Mutations in LRRK2 are the most common cause of dominantly inherited PD. A proportion of LRRK2 PD cases exhibits Lewy pathology with accumulation of α-synuclein and other ubiquitinated proteins in intraneuronal aggregates that is indistinguishable from idiopathic PD. LRRK2 is a multi-domain protein with both GTPase and kinase activities that has been shown to affect various cellular processes including protein homeostasis. However, how PD mutations in LRRK2 may lead to accumulation of α-synuclein and ubiquitinated protein aggregates or may affect inter-neuronal α-synuclein spreading remains unclear.

The aim of this study is to understand the relationship between LRRK2 and α-synuclein and will specifically focus on the role of HDAC6.


Entry Requirements:
• A first class or upper second class honours degree in a biological sciences subject or a related discipline or a Merit or distinction in a suitable MSc. Experience working in a research laboratory is desirable.
• Excellent communication skills in English (speaking and writing).
• Ability to work independently and within a team
• Highly motivated with a commitment to conduct high quality research
• Excellent time management skills
• Experience in cell culture is desirable.
• Experience in immunoblotting and immunohistochemistry is desirable.

Proposed start date: 1 October 2019

Salary/stipend rate: £15,500-£17,000

Enquiries:
Interested candidates should in the first instance contact Dr Kurt De Vos ()

How to apply:
Please complete a University Postgraduate Research Application form available here: http://www.shef.ac.uk/postgraduate/research/apply

Funding Notes

Funding:
Tuition fees and stipend at Home/EU level. Overseas students may apply but will need to fund the difference in tuition fees between the Home and Overseas rate from another source.

Salary/stipend rate: £15,500-£17,000

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