The Roslin Institute
Prion diseases of ruminants, such as bovine spongiform encephalopathy (BSE), scrapie and chronic wasting disease (CWD), are important because of their zoonotic potential, and the economic impact of control measures and trade restrictions on the farming industry. As ruminants are natural hosts of these diseases, they also provide valuable models for comparative studies that can yield insights into related human diseases, such as variant Creutzfeld-Jakob disease (vCJD). There are marked differences between different ruminant species in the pathogenesis and epidemiology of prion diseases. For example, in sheep and deer there is widespread replication of infectivity in lymphoid tissues, and relatively efficient disease transmission between susceptible individuals by a variety of routes, whereas in cattle the infectious agent is largely confined to the nervous system and there appears to be little or no direct transmission of disease. Interestingly, sheep with certain PrP genotypes also demonstrate limited replication of infectivity in lymphoid tissues when infected with prions, and this correlates with relative resistance to disease. I am interested in using a comparative approach in different ruminant species to identify the molecular mechanisms that determine susceptibility to prion infection at a cellular level, and explain differences in host susceptibility and routes of transmission. I am also interested in developing large animal models in cattle and sheep for comparative studies of age-related neurodegenerative changes, as well as the effects of ageing on other body systems.
Examples of proposed research areas: