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Cambridge Infectious Diseases

An Interdisciplinary Research Centre at the University of Cambridge
 

Biography

    Research

    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.

    Publications

    Key publications: 
    • Thackray, A.M., Lockey, R., Beck, K.E., Spiropoulos, J. & Bujdoso, R. (2012). Evidence for co-infection of ovine prion strains in classical scrapie isolates. Journal of Comparative Pathology. Apr 20. [Epub ahead of print].
    • Thackray, A.M., Muhammad, F., Zhang, C., Di, Y., Jahn, T.R., Landgraf, M., Crowther, D.C., Evers, J.F, & Bujdoso, R. (2012). Ovine PrP transgenic Drosophila show reduced locomotor activity and decreased survival. Biochemical Journal. 444: 487-495.
    • Thackray, A.M., Muhammad, F., Zhang, C., Denyer, M., Spiropoulos, J., Crowther, D.C, & Bujdoso, R. (2012) Prion-induced toxicity in PrP transgenic Drosophila. Experimental and Molecular Pathology. 92: 194-201
    • Thackray, A.M., Hopkins, L., Lockey, R., Spiropoulos, J. & Bujdoso, R. (2012). Propagation of ovine prions from poor transmitter scrapie isolates in ovine PrP transgenic mice. Experimental and Molecular Pathology. 92: 167-174.
    • Thackray, A.M., Hopkins, L., Lockey, R., Spiropoulos, J. & Bujdoso, R. (2011). Emergence of multiple prion strains from single isolates of ovine scrapie. Journal of General Virology. 92: 1482-1491.
    • 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.
    Senior Lecturer in Molecular Immunology
    Prion diseases
    Dr Raymond  Bujdoso
    Not available for consultancy