We are seeking a bright and enthusiastic candidate for a PhD studentship in the Neuroscience Institute at the University of Sheffield. You will join a team of researchers from diverse backgrounds all working towards finding new ways to understand and treat neurodegenerative diseases.
During the project you will also collaborate with a major pharmaceutical company with a UK research base where you will undertake training and placements and gain experience of drug discovery in an industrial environment, experience which can be invaluable in the next stages of your career, be it in academia or in industry.
The focus of the project will be on the electrophysiological assessment of cortical hyperexcitability in in vitro and in vivo models of Amyotrophic lateral sclerosis (ALS) and development of new therapeutics to target this pathway.
ALS is a debilitating, progressive and fatal neurodegenerative disorder characterised by degeneration of motor neurons. We know that widespread cortical network dysfunction in the form of cortical hyperexcitability (CH) is a hallmark of ALS. Because cortical circuits control motor neurons within the cortico-spinal tract, hyperexcitability may lead to neuronal loss and dysfunction in ALS [1].
Studies have highlighted that CH is present long before motor neuron dysfunction and loss in ALS [1, 2], suggesting that CH is an early pathogenic influence and increased cortical hyperexcitability in ALS patients correlates with a worsened prognosis [3]. We therefore hypothesise that CH represents an attractive target for development of novel therapeutics in ALS. This studentship will explore this hypothesis using a wide range of models and techniques, providing a solid grounding in neurodegenerative disease research.
You will work with cortical neurons and brain slices from animals models of ALS based on mutations in SOD1, where CH has been identified and targeted using genetic approaches previously [4], and also models based on mutations in TDP-43 and C9orf72. You will assess CH in vitro and in vivo using multi-electrode arrays (MEA) [5, 6] and two-photon imaging. You will develop methods to test novel drugs which may limit CH in these model systems with the intention of further understanding mechanisms and finding new therapeutic approaches.
You will join a thriving postgraduate community in both the Neuroscience Institute and the Sheffield Institute for Translational Neuroscience which not only provides a stimulating scientific environment in which to develop as a scientist but also offers opportunities to build your transferable skills. You will have access to an experienced and hands on supervisory team and excellent pastoral care
At Sheffield we build teams of people from different heritages and lifestyles from across the world, whose talent and contributions complement each other to greatest effect. We believe diversity in all its forms delivers greater impact through research, teaching and student experience. Visit https://www.sheffield.ac.uk/hr/equality for more information.
Aplications 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 an excellent undergraduate degree in a relevant discipline. We would also expect applicants to have completed or be undertaking a relevant master’s degree to a similar very high standard (or have equivalent research experience).
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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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