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SELF-FUNDING MSc BY RESEARCH PROJECT: Developing Drosophila as a model to study the molecular and behavioural changes underlying Parkinson’s disease

School of Physiology and Pharmacology

Bristol United Kingdom Pharmacology

About the Project

The general lab interest is how neural circuit activity underlies behaviour including circadian rhythms, sleep, memory and movement. We study this using Drosophila molecular genetics, behavioural paradigms, electrophysiology, imaging and optogenetics. We wish to elucidate the fundamental biological mechanisms underlying behaviour and elucidate how they are affected by ageing, drugs and diseases such as Alzheimer’s, Parkinson’s, Down’s and schizophrenia.

Parkinson's disease (PD) is the 2nd most common neurodegenerative disease and involves dopamine (DA) neurodegeneration leading to motor and non-motor symptoms. Recent Genome Wide Association Studies (GWAS) for PD have identified ~50 risk loci (Chang et al., 2017). To gain molecular insight into how these genes may lead to PD pathology we will perform an in vivo screen of already available stocks of Drosophila that mis-express the fly orthologues of these risk loci and human PD genes. These transgenes will be expressed in all neurons, all glia or DA neurons and the effect on lifespan, locomotion, circadian rhythm and sleep compared, while neurodegenerative effects will initially quickly be screened in the eye. Genes that yield PD relevant phenotypes will be further characterized for memory defects. Behavioural phenotypes will be further mapped to the most defined populations of cells using the large number of promoters readily available in flies. This will allow for instance the determination of progressive neurodegeneration of subsets of DA neurons mapped to PD relevant behaviours, this is possible in flies as they have only 200 DA neurons in their 150000-neuron brain and live around 60 days. The most promising candidates will be characterised using electrophysiology, optogenetics and mitochondrial live imaging for changes in dynamics and mitophagy (Julienne et al., 2017). 

Funding Notes

This project is for students who can fund the project themselves; there is no financial support.
Please apply to the Faculty of Life Sciences, School of Physiology and Pharmacology, selecting the programme 'MSc by Research'
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Chang, D., Nalls, M.A., Hallgrimsdottir, I.B., Hunkapiller, J., van der Brug, M., Cai, F., Kerchner, G.A., Ayalon, G., Bingol, B., Sheng, M., et al. (2017). A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci. Nature genetics 49, 1511-1516.
Julienne, H., Buhl, E., Leslie, D.S., and Hodge, J.J.L. (2017). Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson's disease phenotypes. Neurobiol Dis 104, 15-23

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