I am primarily interested in membrane proteins. I'm especially interested in channel-forming protein toxins. These proteins are secreted by a wide variety of bacterial species, as well as by plants and even by mammalian cells. Perforin, secreted by T-lymphocytes is an example. Most of my work in this area involves a bacterial channel-forming toxin called aerolysin. We are using a wide variety of molecular biological and spectroscopic tools to study the relationship between the structure of aerolysin and its function.
We have discovered that aerolysin has the remarkable and unique ability to bind to glycosyphosphatidylinositol-anchored proteins on mammalian cells. We are studying the nature of the interaction and using aerolysin as a tool to help unravel the functions of these surface proteins. We are especially interested in reasons for increases in their levels in breast and prostate cancer. We have also exploited the specificity of the aerolysin interaction to develop a diagnostic test for a human disorder called paroxysmal nocturnal hemoglobinuria, in which GPI-anchored proteins are absent.
Also related to my interest in membrane proteins, is a project involving secretion by Gram negative bacteria. Many bacteria are able to secret proteins across both their inner and outer membranes in separate steps. Although the step across the inner membrane has been well characterized, we still don't understand the details of the step across the inner membrane.
My research is supported by the Natural Sciences and Engineering Research Council of Canada, and by the Medical Research Council of Canada.
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January 2001
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