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Cardiff School of Biosciences PhD Studentship: Uncovering the role of the lysosomal NPC1 protein in the pathogenesis of Huntington’s disease (PhD Studentship)

Reference Number: R1021
Closing Date: Closed for applications
Duration: 3 years
Funding Amount: UK/EU tuition fees plus stipend
Level of Study: Postgraduate Research
Regions: EU (Non UK), UK
This funding opportunity is now closed for application

Key Studentship Information

Project Title: Uncovering the role of the lysosomal NPC1 protein in the pathogenesis of Huntington’s disease

Project Description:

The lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders characterised by storage of multiple metabolites within lysosomes leading to cellular dysfunction and death. LSD research has enhanced our knowledge of the mechanisms leading to neuronal cell death in other major diseases including Parkinson’s and Alzheimer’s.

The Lloyd-­-Evans laboratory is interested in Niemann-­-Pick disease type C1 (NPC), a rare neurodegenerative LSD that is characterised by endocytic dysfunction and accumulation of cholesterol and sphingolipids in the lysosomes of all cells. The disease is caused by mutations in the lysosomal NPC1 protein, the only eukaryotic member of a prokaryotic family of multi-substrate efflux pumps called RND permeases. Whilst the exact function of NPC1 remains a mystery it is postulated that it acts as a lipid transporter or even a lipid sensor. Studies in our laboratory have recently identified that NPC1 function is impaired in a number of other neurodegenerative diseases, including Huntington’s disease (HD). Lysosomal dysfunction has been implicated as a contributing factor in HD pathogenesis, however, the mechanisms leading to lysosomal dysfunction in HD are unknown. Our findings that the function of the lysosomal NPC1 protein is impaired in HD are novel, could provide substantial insight into the mechanisms leading to neuronal cell death in HD and yield novel therapeutic targets. The aim of this PhD is to study the role of the NPC1 protein in HD pathogenesis utilizing HD cell lines and animal models. These studies include: i) determining how NPC1 protein function is impaired in HD cells and tissues, ii) characterisation of the similarities in phenotypes between NPC and HD diseases, iii) studying the impact of lysosomal dysfunction on neuronal pathogenesis in HD and, iv) utilising our knowledge of LSD therapies to develop novel treatments for HD. This project is suitable for a biological sciences graduate.

Supervisors: Dr Emyr Lloyd-Evans and Prof Steve Dunnett.

Start Date: 1st October 2013

Number of Awards Available: 1


Funding

This studentship will commence in October 2013 and will cover UK/EU tuition fees and Doctoral stipend of £13,726 p.a.


Eligibility

Academic Criteria: The equivalent of a undergraduate degree at level 2:1 (or higher) in a relevant biological, biomedical or bio-molecular science subject.

Residency: Full awards (fees plus maintenance stipend) are open to UK Nationals and EU students who can satisfy UK residency requirements. To be eligible for the full award, EU Nationals must have been in the UK for at least 3 years prior to the start of the course for which they are seeking funding, including for the purposes of full-time education. EU Nationals who do not meet the above residency requirement are eligible for a fees only award, provided that they have been ordinarily resident in the EU for at least 3 years prior to the start of their proposed programme of study.

English Language Requirement: GCSE/IGCSE grade C or above or IELTS with an overall score of 6.5 and a minimum score of 5.5 in each skill area (or equivalent qualification).


How to Apply

For further details on the project contact Dr Emyr Lloyd-Evans (Lloyd-EvansE@cardiff.ac.uk). Complete the application forms or online application forms, selecting Biosciences as the host department and using “Uncovering the role of the lysosomal NPC1 protein in the pathogenesis of Huntington’s disease” as the research project title.

Application Deadline: 4th March 2013