Role of microglia and innate immune memory on CNS prion disease pathogenesis
Prof N A Mabbott
Dr Abigail Diack
No more applications being accepted
Funded PhD Project (European/UK Students Only)
Funding: This project is eligible for a University of Edinburgh 3.5 year PhD studentship
We seek an enthusiastic Ph.D. student with an appropriate immunology or neurobiology degree to study the influence of innate immune memory in microglia on the development of neuropathology during CNS prion disease.
Prion diseases such as Creutzfeldt-Jakob disease (CJD) in humans, BSE in cattle and scrapie in sheep, are chronic neurodegenerative diseases to which there are no cures. Microglia are the CNS macrophages and help maintain neuronal homeostasis, clear dead/dying cells and provide defence against pathogens. During prion disease an anti-inflammatory cytokine milieu in the CNS stimulates the microglia to provide a host protective role and clear the prions. Recent data suggest that myeloid cells such as microglia can display immune memory effects, contrary to the opinion that immunological memory is restricted to cells of the adaptive immune system. Studies show that acute peripheral exposure to bacterial LPS can influence the subsequent responsiveness of the microglia in the CNS. For example, these treatments can induce epigenetic changes in the microglia that influence the development of neuropathology several months later in an Alzheimer’s disease model. Whether systemic inflammation or co-infection with a gastrointestinal pathogen could similarly influence the subsequent development of neuropathology in other important neurodegenerative diseases such as prion diseases is not known. The aim of this studentship is use unique in vivo models test the hypothesis that the effects of innate immune memory on microglial activation status can modify the progression of CNS prion disease. This studentship will provide excellent training opportunities in state-of-the-art in vivo immunology, bioimaging, cell biology and transcriptomics techniques. A thorough analysis of the factors that influence the progression of CNS prion disease is essential to address important gaps in our knowledge of the factors which affect host susceptibility and help identify novel intervention targets for these currently untreatable neurodegenerative diseases.
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have Home/EU fee status.
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed]
When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.
Mabbott NA, Alibhai JD & Manson JC (2018) The role of the immune system in prion infection. Handbook of Clinical Neurology 153: 85-107. Wendeln AC et al. (2018) Innate immune memory in the brain shapes neurological disease hallmarks. Nature 556:332-338.
Carroll JA, Race B, Williams K, Striebel J & Chesebro B (2018) Microglia are critical in host defence against prion disease. Journal of Virology 92:e00549-18.