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The University of Sheffield
Faculty of Medicine, Dentistry & Health
Department of Neuroscience
Investigation of axonal transport defects in mutant LRRK2-related Parkinson’s disease
Supervisor: Kurt De Vos
Project:
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial
Parkinson’s disease and may also cause sporadic Parkinson’s disease. How mutations in
LRRK2 cause Parkinson’s disease is not known.
Most axonal and synaptic components and organelles are synthesised in the cell body and
transported into and through the axon to their site of action in a process called
anterograde axonal transport. Signals originating at the synapse, and axonal proteins and
organelles destined for autophagy are conveyed back to the cell body by retrograde axonal
transport. The main mechanism to deliver axonal cargoes is microtubule-based fast axonal
transport. Axonal transport is mediated by motor proteins that shuttle cargoes along the
microtubules. Axons contain two types of microtubule-based molecular motors, kinesin
and cytoplasmic dynein, which drive most anterograde and retrograde transport,
respectively.
We now know that axonal transport malfunctions in a number of neurodegenerative
diseases including Parkinson’s disease. We also know that axonal transport malfunction
is one of the earliest, and possibly the earliest defect in these diseases.
Therefore,
understanding how healthy axonal transport works and what causes it to malfunction in
these diseases is very important and is likely to reveal novel drug targets that may be
developed into medicines aimed at sufferers from these diseases.
This project is part of our on-going research into the molecular mechanisms underlying
neurodegenerative diseases and will focus on the role of axonal transport in Parkinson’s
Disease-related neurodegeneration. We will investigate if mutations in LRRK2 disrupt
axonal transport and determine the underlying molecular mechanism.
This research will involve techniques such as advanced quantitative microscopy including
time-lapse and confocal fluorescence microscopy of mitochondrial and vesicle dynamics
and transport, siRNA technology, western blotting and recombinant DNA technology.
Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research
experience.
Enquiries:
Interested
candidates
([email protected]).
should
in
the
first
instance
contact
Kurt
De
Vos
How to apply:
Please complete a University Postgraduate Research Application form and attach at least
two references to your application. To complete the application form please visit:
www.shef.ac.uk/postgraduate/research/apply.
Please clearly state the prospective main supervisor in the respective box and select
‘Neuroscience’ as the department.
'The Medical School has received a Silver Athena SWAN award
for promoting gender equality’
Website: http://www.shef.ac.uk/neuroscience
Closing date: 3rd February 2014