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The research in our laboratory focuses on the development of tools that allows for the generation, analysis and visualization of large-scale, quantitative genetic and physical interaction maps with the ultimate goal of further understanding cell physiology. Our group is presently interrogating a variety of biological processes in different eukaryotic (e.g. yeast, mouse, human) and prokaryotic (e.g. E. coli, B. subtilis, S. typhi) organisms. We are also interested in how these networks change under different conditions in a given organism as well as across different species. Furthermore, our group is also using these global, unbiased systems approaches to understand how HIV (and other pathogens) rewires the host’s cellular machinery during the course of infection. Ultimately, we predict that common host pathways and complexes will be targeted by multiple pathogens, and these will serve as better therapeutic targets for future studies. We recently used a systematic affinity tag/purification-mass spectrometry (AP-MS) approach to purify all 18 HIV-1 polyproteins and processed proteins from two different cell types (HEK293 and Jurkat) and characterized the HIV–human complexes by mass spectrometry. Using a novel scoring algorithm we developed that quantitatively reports on mass spectrometry-derived protein-protein interactions, termed MiST (mass spectrometry interaction statistics), we derived a set of 497 HIV-human protein-protein interactions involving 435 distinct human proteins. This work led to a number of mechanistic insights about the function of specific HIV proteins during the course of HIV infection. We are using other systems approaches to gain a deeper understanding of the HIV infection process. These include analyzing global changes in post-translational modifications in the HIV-infected host proteome, performing genetic interaction analyses with RNAi and mutant viruses. Finally, we are using these platforms to interrogate other pathogenic organisms and how they infect their host, including hepatitis C, influenza and West Nile virus.
- University of Regina, Canada
- University of Toronto, Canada