Research

Our research focuses on dynamics and mechanism of complex biological processes such as: 1) protein folding, 2) protein misfolding and amyloidosis, 3) enzyme functional dynamics, 4) GPCR functional dynamics, and 5) direct molecular imaging of proteins and nanoparticles by MRI. Everyone in the group is exposed to protein expression in E. coli and more recently, yeast, which we use to achieve glycosylation or other post-translational modifications. We also do a fair amount of “chemistry” ranging from completely new synthetic tags for use in NMR studies of proteins expressed from insect cells and yeast or new polymeric formulations for MRI animal imaging of drug delivery systems. Our emphasis is on key systems that relate fundamentally to disease and health – hence the projects that link to misfolding, amyloidosis, and GPCR action with a connection to how drugs activate GPCRs. NMR is a great field to pursue. While useful to organic and protein chemists, I see great potential for growth in NMR and MRI spectroscopy applications in metabolomics and also diagnostic and personalized medicine.

We have several new projects involving protein imaging, protein folding, mechanisms of amyloidosis, GPCR mechanisms of activation, and protein enzymology. We are fortunate to have some great active collaborators including Oliver Ernst at Toronto and Brian Kobilka (Nobel laureate in chemistry, 2012), and three CRC research chairs from across the country, on the amyloid projects. Much of our methodology is quite unique. In many cases, we make use of 19F or (1H-13C) methyl TROSY NMR to detect subtle low-lying states within an ensemble, and piece together a mechanistic description. We have two in-lab NMR magnets with cryogenic probes and plenty of access to additional spectrometers in the Chemistry department downtown. 19F NMR chemical shifts are exquisitely sensitive to molecular environments. Thus, subtle differences in conformation, folding intermediates, or different aggregation states are more likely to be resolved by 19F NMR than by other methods.

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