Department of Veterinary Medicine

Research in Veterinary Medicine

Other relevant links

• Cambridge Neuroscience

Research description

Prion diseases such as scrapie of sheep and goats, BSE of cattle and CJD of humans are transmissible neurodegenerative diseases, characterized by accumulation in the brain of subfibrillar and fibrillar forms of PrPSc, a disease-associated isomer of the host protein PrPC. In some cases, PrPSc may accumulate in peripheral lymphoid tissue prior to prion neuroinvasion of the CNS.

The research of our prion group is concerned with providing knowledge to try and answer some of the important questions relating to aspects of prion disease pathogenesis, diagnosis and therapeutic strategy. These questions include defining the nature of the infectious agent, determining the molecular basis of prion strain diversity, understanding the mechanism of protein misfolding as PrPC converts into PrPSc, and identification of molecular targets for diagnostic and potential therapeutic interventions. These aspects of PrP biology are being pursued in our attempts to identify and quantify abnormal PrP in the blood of individuals with pre-clinical prion disease. These studies underpin our efforts to develop an effective ante-mortem blood test for prion disease.

Our research on PrP involves collaborations with international and national experts in biochemistry, immunology, nanotechnology, protein chemistry and computational analysis of protein folding.

Main collaborators

• Professor Michael Klein: University of Würzburg, Germany
• Professor Edward Hoover: Colorado State University, USA
• Professor Man-Sun Sy: Case Western Reserve University, Cleveland, USA
• Professor Daniel Cox: UC Davis, USA
• Professor Mark Welland: University of Cambridge, UK
• Profesor David Brown: University of Bath, UK
• Dr. Thierry Baron: AFSS, Lyon, France
• Dr. David Burke: University of Cambridge, UK

Key publications since 2001

• Zabel, M., Greenwood, C., Thackray, A.M., Pulford, B., Rens, W. and Bujdoso, R.. Perturbation of T-cell development by insertional mutation of a PrP transgene. Immunology. [Epub ahead of print].
• von Poser-Klein, C., Flechsig, E., Hoffmann, T., Schwarz, P., Harms, H., Bujdoso, R., Aguzzi, A, & Klein, M.A. (2008). Alteration of B cell subsets enhance neuroinvasion in mouse scrapie. Journal of Virology. 82: 3791-3795.
• Fitzmaurice, T.J., Burke, D.F., Hopkins, L., Yang, S., Yu, S., Sy, MS., Thackray, A.M. & Bujdoso, R. (2008). The stability and aggregation of ovine prion protein associated with classical and atypical scrapie correlates with the ease of unwinding of helix-2. Biochemical Journal. 409: 367-375.
• Thackray, A.M., Hopkins, L. & Bujdoso, R. (2007). Proteinase K-sensitive disease-associated ovine prion protein revealed by conformation-dependent immunoassay. Biochemical Journal. 401: 475-483.
• Thackray, A.M. & Bujdoso, R. (2006). Elevated PrPC expression predisposes to increased HSV-1 pathogenicity. Antiviral Chemistry & Chemotherapy. 17: 41-52.
• Encke, J., Bernardin, J., Geib, J., Barbakadze, G., Bujdoso, R, & Stremmel, W. (2006). Genetic vaccination with Flt3-L and GM-CSF as adjuvants: Enhancement of cellular and humoral immune responses that results in protective immunity in a murine model of hepatitis C virus infection. World Journal of Gastroenterology.12: 7118-7125.
• Bujdoso, R., Burke, D.F. & Thackray, A.M. (2005). Structural differences between allelic variants of the ovine prion protein revealed by molecular dynamics simulations. Proteins. 61: 840-849.
• Thackray, A.M., McKenzie, A.N., Klein, M.A., Lauder, A., & Bujdoso, R. (2004). Accelerated prion disease in the absence of Interleukin-10. Journal of Virology. 78: 13697-13707.
• Wong, E., Thackray, A.M. & Bujdoso, R. (2004). Copper induces increased β-sheet content in the scrapie susceptible ovine prion protein PrP-VRQ compared to the resistant allelic variant PrP-ARR. Biochemical Journal. 380: 273-282.
• Thackray, A.M., Klein, M.A. & Bujdoso, R. (2003). Subclinical prion disease induced by oral inoculation. Journal of Virology. 77: 7991-7998.