PhD Studentship: Investigating Mitochondrial Dysfunction in Parkinson's Disease and Assessing Novel Mitochondria-Based Pharmacotherapies

University of Sussex - Department of Neuroscience, School of Life Sciences

A Ph.D. studentship (3.5 years) is available under the supervision of Dr Ilse Pienaar, Department of Neuroscience, School of Life Sciences.

Deadline: 11 May, 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. A Ph.D. studentship (42 months) is available from February 2018 under the supervision of Dr. Ilse Pienaar, School of Life Sciences, University of Sussex, to investigate the molecular basis of our previous findings. In particular, the project will explore the degree of mitochondrial dysfunction that different ‘types’ of neurons undergo, which may be due to oxidative stress, mitochondrial DNA mutations during replication, altered mitochondrial structure and the interaction of pathogenic proteins such, as the aggregate-prone protein α-synuclein with mitochondria, with all these factors that could play a defining role in the neurodegeneration affecting PD patients.

We have also developed novel drug molecules, which will be tested for the ability to target mitochondrial dysfunction and related oxidative stress, and thereby hold significant potential in the treatment of PD. Such testing will occur in induced pluripotent stem cells (iPSCs) taken from PD patients, differentiated to become specific neuronal ‘types’.

This PhD project will allow a student to 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.

Please submit a formal application using our online application system at http://www.sussex.ac.uk/study/phd/apply

Apply for PhD in Neuroscience. Mention name of supervisor in “suggested supervisor” section. In funding mention sponsored or seeking funding. In award details mention School of Life Sciences studentship. Include brief statement of interest (2 pages), CV, two academic references, UG/PGT transcripts and certificates, IELTS results if residing in EU. Only full time UK or EU students will be accepted who hold or expect to attain Masters degree in a relevant subject.

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Type / Role:

PhD

Location(s):

South East England