Department of Veterinary Medicine

Research in Veterinary Medicine

Other relevant links

• Cambridge Neuroscience

Research description

My research interests are concerned with molecular pathology, diagnosis and therapy of conventional and non-conventional pathogens, including viruses and prions. My current research is focused on investigating the molecular nature of the infectious prion agent associated with transmissible spongiform encephalopathies such as scrapie of sheep, BSE of cattle and CJD of humans. One aim of this work is to provide biochemical means of prion strain typing. I am interested in the interactions of pathogens with the immune system, in particular peripheral prion pathogenesis and prion neuroinvasion. My work has involved the generation of novel anti-PrP monoclonal antibodies to probe the structure of PrPC and PrPSc, the generation of recombinant PrP protein for biophysical and biochemical analysis and resultant computational modelling to predict prion protein structure. In addition, my projects involve the use of novel gene knock-out and transgenic mice, cell culture, flow cytometry, immunohistochemistry, in situ hybridisation, RT-PCR, SDS-PAGE, western blotting, protein misfolding cyclic amplification (PMCA), and conformational-dependent immunoassays (CDI). I am actively involved in the development and commercialisation of molecular reagents for prion research and a prion diagnostic test. I also have considerable experience in research into the pathogenesis and chemotherapy of herpesviruses in vivo and in vitro.

Main collaborators

• Professor Michael Klein: University of Würzburg, Germany
• Professor Man-Sun Sy: Case Western Reserve University, Cleveland, USA
• Professor David Brown: University of Bath, UK
• Dr Mark Zabel: Colorado State University, USA
• Dr David Burke: University of Cambridge, UK
• Dr John Spiropoulos: Veterinary Laboratories Agency, Weybridge, UK

Key publications since 2001

• Thackray, A.M., Hopkins, L,. Spiropoulos, J. & Bujdoso, R. (2008). Molecular and transmission characteristics of primary-passaged ovine scrapie isolates in conventional and ovine PrP transgenic mice. Journal of Virology. 82: 11197-11207.
• Yang, S., Thackray, A.M., Fitzmaurice, T.J. & Bujdoso, R. (2008). Copper-induced structural changes in the ovine prion protein are influenced by a polymorphism at codon 112. Biochimica et Biophysica Acta. [Epub ahead of print]. PMID: 18280261.
• Thackray, A.M., Hopkins, L., Klein, M.A. & Bujdoso, R. (2007). Mouse-adapted ovine scrapie prion strains are characterized by different conformers of PrPSc. Journal of Virology. 81: 12119-12127.
• Thackray, A.M., Fitzmaurice, T.J., Hopkins, L. & Bujdoso, R. (2006). Ovine plasma prion protein levels show genotypic variation detected by C-terminal epitopes not exposed in cell-surface PrPC. Biochemical Journal. 400: 349-358.
• Thackray, A.M., Ryder, S.J. & Bujdoso, R. (2005). Modification of blood cell PrP epitope exposure during prion disease. Biochemical Journal. 390: 563-571.
• Thackray, A.M., Yang, S., Wong, E., Fitzmaurice, T., Morgan-Warren, R., & Bujdoso, R. (2004). Conformational variation between allelic variants of ovine cell surface prion protein. Biochemical Journal. 381: 221-229.
• Thackray, A.M., Madec, J-Y., Wong, E., Morgan-Warren, R., Brown, D., Baron, T. & Bujdoso, R. (2003). Detection of bovine spongiform encephalopathy, ovine scrapie prion-related protein (PrPSc) and normal PrPC by monoclonal antibodies raised to copper-refolded prion protein. Biochemical Journal. 370: 81-90.
• Shaw, M.M., Gürr, W.K., Thackray, A.M., Watts, P.A., Littler, E. & Field, H.J. (2002). Temporal pattern of herpes simplex virus type 1 infection and cell death in the mouse brain stem: influence of guanosine nucleoside analogues. Journal of Virological Methods. 102: 93-102.
• Thackray, A.M., Klein, M.A., Aguzzi, A. & Bujdoso, R. (2002). Chronic subclinical prion disease induced by low dose inoculum. Journal of Virology. 76: 2510-2517.
• Thackray, A.M., Knight, R., Haswell, S.J., Bujdoso, R. & Brown, D.R. (2002). Metal imbalance and compromised antioxidant function are early changes in prion disease. Biochemical Journal. 362: 253-258.