PhD Studentship: Deciphering Cell-type Specific Effects of P2X7R Antagonism in Lewy Body Dementia

Location: Clinical and Biomedical Sciences, Streatham Campus, Exeter 

The University of Exeter’s Department of Clinical and Biomedical Sciences is inviting applications for a PhD studentship funded by BRACE to commence on 24 September 2024 or as soon as possible thereafter. For eligible students the studentship will cover Home tuition fees plus an annual tax-free stipend of at least £19,237 for 3 years full-time, or pro rata for part-time study. The student would be based in Clinical and Biomedical Sciences in the Faculty of Health and Life Sciences at the Streatham Campus in Exeter. 

Project Description:

Lewy body dementia (LBD) is an umbrella term for diseases including dementia with Lewy bodies and Parkinson’s disease dementia, which are characterised by abnormal aggregation and deposition of asynuclein (aSyn) in affected regions of the brain. There are no available therapies for LBD. This is in part due to incomplete understanding of the mechanisms underlying these diseases. In recent years, it has become apparent that inflammation in the brain contributes to the progression of dementia, and strategies to treat dementia by reducing inflammation are under investigation. P2X7R is a receptor that is predominantly expressed by non-neuronal cells in the brain and that is considered a master regulator of brain inflammation. This project will explore the contribution of P2X7R to Lewy body dementia. It will explore overall beneficial effects of P2X7R block, and determine how this receptor affects disease progression so that we can hone future treatment strategies. To do this, the project aims are to determine (i) in which type of brain cells P2X7R is acting to affect LBD progression, and (ii) the biological pathway responsible for providing protection upon receptor blockade. The project will build on our recently published work in which we showed that P2X7R is expressed in astrocytes and microglia in human brain, directing different types of inflammation in each cell type. Here, we aim to progress this work by determining the cell type through which P2X7R affects a-synuclein aggregation in a model of LBD and the precise pathways involved. This work also has relevance to AD since recent studies show an association of aSyn accumulation with cognitive decline in AD. This information gained from the project can be used to develop more effective P2X7R-based therapies and, importantly, to enable the development of strategies that can better track the effectiveness of future P2X7R-targetted drugs for dementing diseases. This project is a collaboration between the University of Exeter, King’s College London (Dr Maria Jimenez-Sanchez) and University College London (Dr Cara Croft).

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