Knox, David - University of Manitoba - Department of Medical Microbiology and Infectious Diseases

研究领域

The appearance of a novel infectious form of human prion disease, vCJD, in the United Kingdom from 1995 onward is thought to be due to dietary exposure to infected beef tissue. While the number of vCJD cases appears to be on the wane recent experimental evidence has demonstrated that prions can replicate to high concentrations in animal models without causing clinical disease. This raises the spectre that there may be a large population of people harbouring subclinical forms of the disease and that materials such as blood products derived from these people may be highly infectious. In the absence of a diagnostic test for preclinical disease this question will only be answered a decade hence by the absence or appearance of a new wave of vCJD. The objective of the programme is to use comparative genomics and proteomics to identify differentially expressed host genes and proteins characteristic of TSE infection. The identification of these alternative markers will provide insight into the pathogenesis of the diseases, identify potential therapeutic targets, and potentially lead to the development of a diagnostic test. The programme will use cultured neurons and various animal models to explore the mechanisms of pathogenesis, the efficacy of various therapies, and to assess the prognostic potential of the genes identified. The research platforms in place include, DNA microarray analysis, Real-Time PCR, immunohistochemistry, 2-D Fluorescence Difference Gel Electrophoresis (DIGE), tandem mass spectrophotometry

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Plews M, Lamoureux L, Simon SLR, Graham C, Ruddat V, Czub S and Knox JD: Factors Affecting the Accuracy of Urine-Based Biomarkers of BSE. Proteome Science, 9:6. 2011. Lamoureux L, Simon SLR, Plews M, Stobart M, Groschup M, Czub S, Graham C and Knox JD: Analysis of Clusterin Glycoforms in the Urine of BSE Infected Fleckvieh-Simmental Cows. J Toxicol Environ Health, 74:138-145. 2011. Plews M, Simon SLR, Boreham DR, Parchaliuk D, Wyatt H, Mantha R, Frost K, Stobart M, Mitchel RE and Knox JD: A Radiation Induced Adaptive Response Prolongs the Survival of Prion Infected Mice. Free Radical Bio Med, 49:1417-1421. 2010.