High resolution characterization of macromolecular structure and dynamics

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Funds requested in this NSERC Research Tools and Instruments (Category 1) grant application will be used to purchase a state-of-the-art and new-to-market Size Exclusion Chromatography Multi-Angle Static Light Scattering (SEC-MALS) system and to upgrade a multiuser analytical ultracentrifugation system. Both systems are complementary to each other and allow the detailed biophysical characterization of proteins and other biomolecules by obtaining accurate molecular weights and oligomeric states of the samples. The instruments allow for the direct detection of protein conformational changes, protein dynamics, protein stability, and protein-ligand interactions among many other applications. These instruments are critical to the research carried out by our team aimed globally at characterizing protein structure and function in different model systems. The team consists of eight Principal Investigators who have worked together and published together on several different projects. In addition, the instruments will be made available for use to the community in general by being placed at the Protein Biophysics Center located in the Department of Biochemistry at the University of Toronto. In addition to members of our groups, students and postdoctoral fellows from about 40 other groups routinely use the biophysical instruments at the Center, which houses a high end fluorometer, plate reader, circular dichroism spectropolarimeter, a mass spectrometer, isothermal titration calorimeter, among other instruments. Research by those groups is in the general area of protein folding and interaction dynamics. Having these state-of-the-art systems as part of the Protein Biophysics Center will ensure a rich research environment for our trainees. The center will attract top undergraduate and graduate students and post-doctoral fellows who will have access to a comprehensive array of the latest biophysical technologies in a totally integrated and managed environment. This will be of great importance to keep our groups at the forefront of the field of protein biophysics.