Summary of Research
The transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases affecting humans and animals. TSEs present with characteristic pathology which can include neuronal loss, reactive astrogliosis, deposition of disease-associated prion protein (PrP) which may form amyloid plaques, and vacuolation giving a characteristic spongiform appearance to brain tissue. The aim of our group is to examine the role of host PrP in the outcome of natural TSEs like scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakobs disease (CJD) as well as a large range of experimental TSE models available in the Neurobiology Division. Basic research into neurodegenerative processes has also led into study of other diseases such as Alzheimer's disease
The group uses a variety of models from the molecular to whole animal level of study. In particular we have produced a battery of unique transgenic mouse models via gene-targeting including:
• PrP knockout
• PrP species gene replacement
• Conditional (Cre/LoxP) PrP models
• PrP N-glycosylation site deficient models
The gene targeting approach ensures that the altered PrP allele remains in the correct genomic location under control of the endogenous promoter thus avoiding PrP over-expression that may lead to altered phenotypes. These models allow the group to investigate the effects of PrP sequence and glycosylation and also expression in various cell-types or at specific time-points during disease.
The group also employs a sheep model for investigation into transfer of TSE infection via blood transfusion, particularly relevant to the current identification of secondary transmission of new variant CJD in humans by the same route.
Our research programme currently receives funding from a number of different sources including BBSRC, MRC, DEFRA, DoH and EU.