Investigating mitochondrial dysfunction in Parkinson’s disease and assessing novel mito-chondria-based pharmacotherapies (2018)

What you get

You receive:

• fully-funded tuition fees for 3 and a half years
• £14, 777 grant for living costs for 3 and a half years
• Traning/research support grant for 3 and half years (we'll confirm the amount at the start of the project)

Type of award

Postgraduate Research

PhD project

Supervisor: Doctor Ilse Pienaar

School or department you’ll be based in: School of Life Sciences

Start date: September 2018

Profound cholinergic neuronal loss occurs in brainstem structures of Parkinson’s disease (PD) patients compared to age-matched control cases.

This loss is believed to underlie the gait disturbances seen in PD patients. Previously, our group (Pienaar et al. 2013) reported loss of neurons producing γ-aminobutyric acid (GABA) and glycine, two major inhibitory neurotransmitters.

Interestingly, when expression of proteins that play a key role in the mitochondrial electron transport chain (for producing energy (ATP) to meet energy demands of the cells) were evaluated, significant up-regulation of such proteins were seen in GABAergic and glycinergic neurons; however, cholinergic neurons showed down-regulation of the same proteins.

More recently, we also showed that in PD, single cholinergic neurons from this region have mitochondrial ‘copy number’ changes the opposite to that seen in another vulnerable group of neurons, dopaminergic ones (Pienaar et al. 2017).

These findings lead to intriguing speculations as to cells-specific mechanisms that could underlie deep brain stimulation (DBS) of this region, which improve gait disturbances in PD patients.

You will investigate the molecular basis of our previous findings.

In particular, you will explore the degree of mitochondrial dysfunction that different ‘types’ of neurons undergo, which may be due to:

• oxidative stress
• mitochondrial DNA mutations during replicationaltered
• mitochondrial structurethe interaction of pathogenic proteins such as the aggregate-prone protein α-synuclein with mitochondria.

All these factors could play a defining role in the neurodegeneration affecting PD patients.

You’ll gain expertise in

· mitochondrial genetics,

· genomics,

· medicinal chemistry,

· biochemistry (particularly mitochondrial bioenergetics),

· cell culturing technologies,

· and computational modelling, applied to understanding the progressive neurodegeneration seen in PD.

These findings lead to intriguing speculations as to cells-specific mechanisms that could underlie deep brain stimulation (DBS) of this region, which improve gait disturbances in PD patients.

Eligibility

To be eligible, you must:

• be a UK/European Union (EU) national
• have a Masters, or a Masters-level qualification in relevant subject area
• hold a valid IELTS qualification (or similar) if you are a non-UK applicant

 

Deadline

11 May 2018 23:45

How to apply

 

 

pply for a Neuroscience PhD using our postgraduate application system. When you apply, you need to include:

• your supervisor’s name in the ‘Suggested supervisor’ section
• School of Life Sciences funded studentship in the ‘Awards detail’ section
• a two-page statement of interest
• two academic references
• Bachelors and Masters transcripts
• your IELTS results if you are not from the UK.

You normally find out outcome of your application four weeks after the application deadline.

 

Contact us

Contact Anna Izykowska (a.izykowska@sussex.ac.uk) with any application queries.

Contact Dr Ilse Pienaar (I.S.Pienaar@sussex.ac.uk) with questions about the project.