A major limitation in treating neurodegenerative diseases is a lack of early diagnosis. However, many neurodegenerative diseases (including Motor Neurone Disease and Parkinson’s) exhibit neuronal hyperexcitability early in disease progression. Previously we demonstrated that hyperexcitability within the visual system precedes neurodegeneration in our established animal (fruit fly and mice) models of Parkinson’s Disease [1-5]. Detection of these changes in visual responses allowed us to accurately classify between animals with and without disease causing mutations, as well as monitor disease progression [2, 4]. With visual dysfunction reported in patients with a range of neurodegenerative diseases accurate detection and monitoring of visual disturbances represents a unique opportunity for early-diagnosis, monitoring disease progression and as a pre-clinical drug-discovery research tool. However, current systems for monitoring visual responses rely on large, expensive and specialist equipment. In order to accelerate a bench-to-bedside approach this project looks to develop a single, affordable, portable technology for monitoring neuronal activity within the visual system in both pre-clinical research (animal models) and clinical diagnostic settings. Combining psychophysics, computer science, engineering and neuroscience this interdisciplinary project will provide a bridge between pre-clinical and clinical research, supporting early diagnosis and monitoring of disease progressions and pre-clinical drug-discovery, as part of a dynamic translational pipeline.
The project has 3 major components:
1. Equipment development - the student will explore the use of single-board-computers (e.g. Raspberry pi) and standard off-the-shelf components to develop a portable system in which visual stimuli can be presented to animal (fruit fly) models of neurodegenerative diseases and steady state visually evoked potential (SSVEPs) electroretinogram (ERG) recordings made. The student will be responsible for developing and building the equipment as well as for developing data acquisition and analysis codes and an intuitive, user-friendly, web-based interface, supporting use by users of varying experience
2. Genetic Dissection and Drug-Discovery – having tested the setup on our previously characterised models of Parkinson’s disease the student will explore whether alterations in vision are conserved across a range of Drosophila (fruit fly) models of neurodegenerative diseases. They will then use powerful genetic dissection available in these models to unravel the molecular mechanism underpinning neurodegeneration. The student will also explore whether neurodegeneration and alterations in vision can be rescued by administering potential therapeutic compounds.
3. Translation to clinic - In order to facilitate translation to clinical settings, supporting a bench-to-bedside diagnostic approach, the student will develop an interface between our portable setup and clinical, potentially through interfacing with existing wireless EEG headsets. System development will be performed by testing in healthy volunteers, with potential to draw on existing clinical cohorts of patients with MND and PD.
The outlined proposal provides a unique opportunity for a student to undertake a PhD at the interface between disciplines, combining basic and translational neuroscience, psychophysics, engineering and computational systems biology. Training will be provided in all aspects of Drosophila husbandry and SSVEP ERG electrophysiology using specialist equipment for both animal models (West lab (http://sitran.org/people/west/)) and human participants (Milne lab, Sheffield Autism Research lab (ShARL) (https://autismresearchlab.group.shef.ac.uk/)). Based in SITraN (http://sitran.org/), a world leading centre dedicated to understanding neurodegenerative diseases, the student will have full access to a range of state of-the-art facilities including a fully equipped Drosophila lab, drug-screening facility and electrophysiology lab.
Candidates must be able to show evidence of the relevant experience in programming and the basic electrical engineering skills required.
Applications are open to students from both the UK and overseas, though we note that due to funding constraints the availability of positions for students with overseas fee status will be more limited. We anticipate competition for these studentships to be very intense. We would expect applicants to have completed or be undertaking a relevant master’s degree to a similar very high standard (or have equivalent research experience).
Informal enquiries should be made to Dr Ryan West ([Email Address Removed]).
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Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgradapplication/
Please clearly state the prospective main supervisor in the respective box and select ‘Neuroscience’ as the department.
After the application closing date, we will shortlist applicants for an online interview. We expect to carry out interviews (each lasting approximately 30 minutes) on Tuesday 27th April (am, GMT) and Tuesday 4th May (pm, GMT). If you are shortlisted for interview, we will aim to inform you of this no later than the end of Friday 23rd April. If you are unable to attend at the specified times, please let us know if we confirm that we would like to interview you.
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