Project title: Analysis of Drosophila models of Parkinson’s disease – the GBA link

Project supervisor: Dr Alex Whitworth (BMS & CDBG)

Application deadline: Friday 14 December 2012.

Project description:

Genetic risk factors are likely to comprise an important contributor to the pathogenic cause of Parkinson’s Disease (PD) in sporadic cases (Gasser et al. 2011). One example of such a risk factor is mutations in GBA, encoding glucocerebrosidase. Homozygous mutations cause the lysosomal storage disorder Gaucher's disease whereas heterozygous carriers are at significantly higher risk for getting PD and is a major risk factor in certain ethnic groups (Sidransky et al. 2009).

The potential contribution of GBA dysfunction to PD may be substantial but the pathogenic cause is unknown. It is also likely that risk factors may contribute to pathogenesis by affecting mechanisms linked to the genetic causes. Drosophila has proven to be a remarkable simple model system for the elucidation of basic mechanisms of neurodegenerative diseases including PD (Whitworth, 2011).

In this project we will use a combination of techniques, primarily using the powerful genetic approaches in Drosophila coupled with molecular and cell biology techniques, to analyse the pathogenic effects of GBA mutations linked to PD and elucidate the mechanisms by which they cause neurodegeneration. We will also work closely with our collaborators in the UK Parkinson’s Disease Consortium (UKPDC) to extend our analyses to mammalian systems.

This project is available to start Spring 2013 or Autumn 2013, and is open to UK and EU students. International students may also apply but the higher fee status will need to be covered by additional funds or competitive award of a fee waiver.

References:

• Gasser T, et al. (2011).
  "Milestones in PD genetics."
  Mov Disord 26 (6): 1042-8.
• Sidransky E, et al. (2009).
  "Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease."
  N Engl J Med 361 (17): 1651-61.
• Whitworth AJ (2011).
  "Drosophila models of Parkinson's disease."
  Adv Genet 73: 1-50.

Contact Details:

Dr Alex Whitworth

Web: http://www.shef.ac.uk/bms/research/whitworth

Email: a.whitworth@sheffield.ac.uk