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Our laboratory is located in Room 133 Sieben's-Drake Research Institute Dr. McCormick is Assistant Professor in the Dept of Microbiology & Immunology, Scientist in the Lawson Health Research Institute, and a member in the Canadian Research and Development Centre for Probiotics and Infectious Diseases Research Groups. He holds a New Investigator Award from the Canadian Institutes of Health Research. |
Our Research
1) Structure-function and molecular biology of bacterial superantigens from Streptococcus pyogenes.
Bacterial superantigens are a class of extremely potent toxin secreted by strains of Streptococcus pyogenes (group A streptococci) and Staphylococcus aureus that are directly implicated in the pathogenesis of toxic shock syndrome, scarlet fever and other immunological disorders. Bacterial superantigens are also likely major virulence determinants in invasive streptococcal diseases such as necrotizing fasciitis/myositis ("flesh eating disease"). These toxins function by causing a remarkable expansion of T cells such that the frequency of T cells responding to superantigen exposure exceeds that of conventional peptide antigens by several orders of magnitude. Conventional antigens, when presented in the context of major histocompatibility (MHC) molecules on antigen presenting cells, are recognized by the alpha and beta variable domains (Valpha and Vbeta, respectively) of the T cell receptor (TCR). In contrast, superantigens bind directly to the Vbeta domain of the TCR and to lateral regions of the MHC outside of the peptide binding groove (they do not need to be processed by an antigen presenting cell) and thus can bypass the normal antigen presentation pathway. As a result of these interactions, conventional antigens may stimulate in the order of less than 1 in 10,000 T cells, while superantigens may stimulate up to 20% of all T cells. Furthermore, these toxins are extremely potent in that significant T cell proliferation is detected for some superantigens in the picogram (10-12 g) per ml range. The immediate outcome of this interaction is the large expansion of T cells with the resulting massive release of host cytokines that are believed to be responsible for the most severe consequences of the superantigens. The high fatality rates of severe streptococcal disease and long recovery periods indicate that novel therapeutic strategies are required, and a better understanding of streptococcal virulence will be necessary to develop alternative approaches for treatment. Furthermore, because bacterial superantigens activate T cells, or can induce T cell deletion and anergy, a broad collective understanding of superantigen biology may lead to the realization of new immunomodulatory therapies such as anti-tumour treatments.
2) Genetics and biotechnology of probiotic lactobacilli.
Lactobacilli represent an important group of lactic acid bacteria that are commonly associated with the mammalian gastrointestinal (GI) and vaginal tracts. The word "probiotic" is a term that is being used for specific strains of bacteria, typically lactobacilli and bifidobacteria, that when administered can provide clinically proven health benefits to their host. Today, the field of probiotics is exploding with the genomics revolution such as with the recently released genomic sequences from Bifidobacterium longum and Lactobacillus plantarum, as well as the many genomes from lactic acid bacteria that are being completed. This information is expected to provide many new insights into the molecular mechanisms underlying key beneficial interactions of probiotics with their human and animal hosts. However, despite this great promise and enthusiasm in using probiotics for human and animal health, specific mechanisms as to how these bacteria provide their proposed benefits are generally scarce. Research in our group is using a combination of approaches to design probiotic strains to act as delivery agents for novel therapeutics such as anti-infective agents and anti-cancer therapies. We are also investigating important cell-cell signalling events between probiotic bacteria with important bacterial pathogens. Finally, we are examining the molecular mechanisms underlying the ability of lactobacilli to colonize the intestinal and vaginal tracts, including specific surface proteins for their role in promoting health by inhibiting adherence of pathogenic bacteria.
