Systemic infections accelerate tau spreading by promoting glial activation

Alzheimer’s disease (AD) is a neurodegenerative disease, with a complex biology. In this PhD project, we aim to explore the cellular and molecular mechanisms underlying tau pathology. The results may lead to improved understanding of the biological mechanism underlying spreading of Tau in the AD-affected brain. Build-up of ‘amyloid plaques’ in the brain is recognized as an early feature of AD, but the presence of tau tangles and/or inflammation better predicts memory loss. Tau tangles can spread through the brain affecting a whole network of neurons. Using an experimental model of AD, we showed that systemic inflammation accelerates the spreading of tau, possibly due to activation of microglial cells. In this PhD studentship we aim to explore the cellular and molecular mechanisms underlying accelerated tau pathology following systemic inflammation. The student will use an experimental model to study the effect of a real live, systemic bacterial infection on glial activation, tau pathology and amyloid load. By exploring different time points we aim to identify how, and when, different cell types contribute to the spreading of tau. Using a range of advanced molecular techniques, the student will investigate how glial cells and neurons interact and organize across the tissue landscape, using both mouse and human tissue. As bacterial infections can be treated, understanding the connection to the brain may lead to novel treatment and outcomes of AD patients.

This interdisciplinary PhD studentship, funded by Alzheimer’s Research UK, is a collaborative project between the University of Southampton and the University of Exeter. We are looking for a highly motivated candidate who will benefit from training in a range of techniques, including in vivo models, immunohistochemistry, advanced imaging, spatial transcriptomics and computational modelling. The project is funded for 3.5 years and welcomes applicants from the UK who have or expect to obtain at least an upper second-class degree in Biological Sciences or allied subjects. Funding will cover fees and a stipend at research council rates of £19,000 per annum.