Using vision as a window into Parkinson's Disease

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Whilst commonly considered to be a motor disorder, Parkinson's Disease is also characterised by changes in vision. Using methods derived from human vision science, we have shown that mutations known to cause early onset Parkinson's disease result in hyperexcitability in the Drosophila (fruit fly) visual system. This, in turn, leads to excitotoxicity and vision loss as the flies age. Translating this methodology back to humans, our preliminary findings show that the same changes in the visual system are observed in Parkinson's patients. We therefore propose that vision may provide a reliable biomarker that can be used to diagnose and monitor progression of Parkinson's disease. This interdisciplinary, translational project will combine animal (Drosophila) models for drug discovery screens and dissecting the molecular mechanisms underpinning disease with the study of human participants to optimise and translate this protocol for use as a clinical diagnostic tool. You will be based in the Sheffield Institute for translational neuroscience (SITraN) a vibrant interdisciplinary research institute bringing together both basic researchers and clinicians under one roof. Working with Dr Ryan West (SITraN), an expert in Drosophila models of neurodegeneration, you will identify novel compounds that alleviate Parkinson's disease phenotypes, including visual dysfunction, in Drosophila models. You will also utilise the advanced genetic toolbox of Drosophila to dissect the molecular mechanisms underpinning disease. Working with Professor Alex Wade (York) at the York Neuroimaging Centre (YNiC), you will translate the assays used in Drosophila into robust neuroimaging measurements (fMRI/MEG/EEG/fNIRS) that can be used to objectively assess the health of the human visual system with a particular focus on 'early' visual processing stages: the extraction of luminance, colour and contrast. Once these assays are established, you will work with Dr Melanie Burke (Leeds) in the Brain and Behaviour Lab to develop clinically appropriate versions of these assays in human participants, using brain imaging (fNIRS) and eye movement measures to establish their sensitivity to Parkinson's disease.