Propagation of mammalian prions in PrP transgenic Drosophila. Prion diseases are infectious, fatal, neurodegenerative conditions of humans and various animal species. They include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. Collectively, these diseases may be inherited, arise sporadically or occur through exposure to infectious prion material. Zoonotic transmission of prion disease is a significant threat to public health as evidenced by the BSE epidemic in UK cattle and subsequent emergence of variant CJD in humans, which is believed to have occurred through consumption of prion-contaminated bovine products. The emergence of new prion strains, such as atypical scrapie in sheep and bovine amyloidotic spongiform encephalopathy (BASE) in cattle, with unidentified risks to human health, highlight the need to characterise potentially zoonotic prion strains in animals within the human food chain. Since the molecular nature of the infectious prion agent is undefined, the only reliable method to determine transmission properties of different prion strains and measure prion infectivity has been by bioassay in an appropriate indicator species. We have begun to establish Drosophila as a new animal model to assess ovine prion infectivity in pursuit of a more tractable model of transmissible mammalian prion disease. This project will investigate mammalian prion propagation in Drosophila, the mechanism of prion-induced neurodegeneration and the identification of genetic modifiers that may regulate these processes.
- Thackray AM, et al. (2012a). Biochem J 444: 487-495
- Thackray AM, et al. (2012b). Exp Mol Pathol 92: 194-201