Proteomics-based Direct Diagnosis

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This NSERC Collaborative and Research Development Grant proposal represents an exciting collaborative opportunity between a Canadian biotechnology company, Vancouver Island Antibodies Ltd., that specializes in SISCAPA® immuno-mass spectrometry-based diagnostic technology, a Canadian university-based research team (Cameron laboratory) located at the University of Victoria with novel expertise in spirochete biology and diagnostic antigen discovery and development, and a research team at the Institute of Tropical Medicine in Antwerp, Belgium (Kenyon laboratory) with expertise in proteomics and biomarker discovery. This proposal focuses on the measurement of microbial biomarkers in urine and plasma samples, using novel technology, to enable direct diagnosis of active infections. As a result of the combined expertise of the Cameron and Kenyon labs within the field of spirochete research, we will focus upon four economically important and globally prevalent infections: syphilis (caused by Treponema pallidum subspecies pallidum), yaws (caused by Treponema pallidum subspecies pertenue), leptospirosis (caused by Leptospira species) and Lyme disease (caused by Borrelia burgdorferi). Unlike other diagnostic methods, SISCAPA®technology measures antigens from the infecting organism thus improving on current sub-standard diagnostics. The method involves three main steps: (1) identification of unique spirochete proteins that are expressed at a sufficient levels during infection, subsequent selection of key proteotypic peptides as protein surrogates and derivation of affinity-purified antibodies specific for these peptides; (2) testing of the antibodies for their ability to enrich the surrogate peptides and analysis of their lower limits of detection by mass spectrometry and (3) testing of samples (urine and plasma) for diagnostic identification of active infection. The project will have significant economic benefit for Canada through training of highly skilled workers, enhancement of research and development and the establishment of a diagnostic platform that can successfully diagnose diseases that have a global distribution, are economically relevant and have historically been difficult to diagnose.