Parkinson’s disease (PD) is traditionally thought of as a motor disorder, but it also affects dopaminergic neurons in the visual system, resulting in altered visual sensitivity. Using the genetic power of Drosophila (fruit flies) as a model of Parkinson’s disease recent publications from our labs have shown that hyperexcitation in the visual system occurs early in Parkinson’s disease progression, proceeding typical motor dysfunction and later stage neurodegeneration. Hyperexcitability within the visual system can, therefore, be used as a sensitive biomarker of neurodegeneration. We have also shown that state-of-the-art machine learning algorithms can accurately identify the specific disease-causing mutations in different genetic models of Parkinson’s based solely on the information present in visual responses.
Our goal is to understand the mechanisms that give rise to these findings in animal models and to translate the measurement techniques to humans, allowing us to build a rapid, accurate and non-invasive method for diagnosing and monitoring Parkinson’s disease.
The student on this interdisciplinary, translational project will use Drosophila models of Parkinson’s disease, under the supervision of Dr Ryan West (Sheffield), to dissect the genetic and molecular mechanisms underpinning visual dysfunction and neurodegeneration in Parkinson’s. They will learn to combine molecular biology and cutting-edge genetic techniques with systems neuroscience techniques such as in vivo electrophysiology, signal processing including time-series analysis and machine learning. Drosophila models will also be used to perform drug-screens, identifying compounds for future clinical translation.
To translate our findings to a clinical setting, this work on animal models will be combined with neuroimaging studies on human participants, under the supervision of Professor Alex Wade (York) and Dr Melanie Burke (Leeds). The student will therefore also learn to perform human neuroimaging in both healthy subjects and PD patients. Advanced training in human neuroimaging will span a range of methodologies (fMRI/MEG/fNIRS) both at the York Neuroimaging Centre (YNiC) and at the Brain and Behaviour Laboratory in Leeds. With the support of dedicated research staff, students will design, run and analyse complete neuroimaging experiments with a focus on translating visual biomarkers of PD from animal models to human patients.
The student will be based in the Sheffield Institute for Translational Neuroscience (SITraN), an award-winning centre dedicated to the study of neurodegenerative diseases. Frequent visits to the neighbouring cities of York and Leeds will be required.
Once these techniques have been established there will be future opportunities to extend them to other neurodegenerative diseases that are known to alter visual processing including dementia and epilepsy.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme and how to apply can be found on our website:
http://www.dimen.org.uk/how-to-apply/application-overview
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