The role of Topoisomerase II beta Neuronal DNA repair in aging (HLS/SE/DRFAPP7P/63601)

Neurons show high levels of metabolic active which results in the production of oxidative stress. However this is counterbalanced by a robust repair system in these cells. The enzyme DNA topoisomerase II beta (Top2B) is required for double stand break repair in neurons and also influences repair of DNA damage by oxidative stress, thus it is a key player in maintaining genomic integrity of these cells. This process is important as many neurodegenerative diseases such as Alzheimer’s disease cause the accumulation of oxidative stress in their early stages, which if go unrepaired may lead to further aberrant neuronal cell function and death. However, several mammalian studies suggest that Top2B is down-regulated in aged neurons. So understanding the impact of this upon DNA repair is an important step in elucidating the effect of aging upon levels of DNA damage in these cells. Thus the focus of the project is to investigate whether down-regulation of Top2B in aged neurones is correlated with decreased levels of DNA repair and decreased transcription of key genes in these processes which may be influenced by the action of Top2B. In addition, cell lines models will be used to test whether epigenetic up regulation of Top2B levels can modulate repair mechanisms and transcription in neurons to determine whether this would be a useful potential strategy for cell therapy.

Informal Enquiries
Enquiries regarding this studentship should be made to: Dr Kay Padget [Email Address Removed]
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Eligibility
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How to Apply
For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
Please ensure you quote the advert reference above on your application form.