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 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).
Hereditary spastic paraparesis (HSP) and hereditary cerebellar ataxias (HCA) are heterogeneous groups of progressive neurodegenerative conditions with significant overlap. One of the commonest causes of combined cerebellar ataxia and mild spastic paraparesis is SPG7. In Sheffield we are home to the largest single centre cohort of SPG7 patients in the UK with over 60 patients. These patient’s phenotype is well characterised with longitudinal data on disease progression (Hewamadduma et al 2018). Mutations in this gene are commoner than previously thought. It is the commonest autosomal recessive gene in HSP and second commonest in HCA. This group of patients follow a progressive course and suffer accumulating disease burden of spasticity, ataxia, optic atrophy, dysarthria, cognitive impairment with significant deterioration in mobility (Coarelli et al 2019). So far there is no cure and there are only a very few studies aiming to understand the natural history of the disease. Limited studies have investigated the pathophysiology of SPG7 but there is none on investigation of small molecule screening or mitochondrial DNA damage and repairing factors, in relation to SPG7. Furthermore to our knowledge there are no systematic biomechanical studies characterising gait in SPG7 to identify gait-related-biomarkers except our group in Sheffield. There are also gaps in longitudinal characterisation of neuro radiological markers of SPG7.
In our group we have several studies investigating longitudinal gait monitoring data using a single sensor in HSP and mult modal MRI studies characterising SPG7 patients. We have are continuing to systematically assess SPG7 patients with advanced MRI techniques to identify radiological biomarker. Patient derived cell models have been established to study cellular biomarkers and DNA repair and mitochondrial dysregulation. Correlation between Multi modal radiological markers and clinical, gait and cellular biomarker data already collected, will enable us to begin to explore novel bio markers. Computational technologies will be utilised to generate prediction of disease states.
Student will receive training and support with regards to radiological image analysis, computational modelling and gait analysis methods. The student will attend clinic to continue to gather clinical data under Dr Hewamadduma. This project allows the student with the rare opportunity of working very closely with leading clinicians and researchers of the field with a unique but a large cohort of well characterised patients.
Please complete a University Postgraduate Research Application form available here: http://www.shef.ac.uk/postgraduate/research/apply.
Please clearly state the prospective main supervisor in the respective box and select ‘Neuroscience Institute’ as the department.