James M. Rini

            Our research focuses on coronavirus-receptor interactions and the role played by ER-resident glycosyltransferases in protein folding and subcellular targeting.  In all cases, we take a structural approach using electron cryo-microscopy (Cryo-EM) and x-ray crystallography supported by a range of biophysical and cell-based assays. 

            The coronavirus project is currently centred on the spike proteins of the four seasonal coronaviruses that account for 15-30% of common colds.  The work ranges from receptor identification to efforts aimed at understanding how spike protein conformational changes mediate receptor binding, immune escape and the evasion of decoy receptors.  It is fundamental in nature and seeks to characterize the mechanistic basis for how these coronaviruses have adapted to their human hosts.  Over the long-term this knowledge will be valuable in the development of vaccines and antivirals against emerging coronavirus threats.  Our work on the SARS-CoV-2 spike protein, for example, has already led to the design of candidate multivalent antibody therapeutics and vaccines.  

            Our most recent work in the glycosyltransferase area deals with the protein-O-glycosyltransferases specific for the EGF-like domains found in the Notch receptor and its ligands.  It is not only uncovering how these enzymes ensure the proper folding and targeting of these signaling molecules but the likely role that they played in the evolution of multicellular organisms.  Our work on glycosyltransferases also extends to those that modify N-glycans to mediate ER protein folding and lysosomal enzyme targeting.  How these enzymes recognize their folded and unfolded substrates remains essentially unknown, and the goal is to fill that knowledge gap through structural and biochemical analysis.  Proper functioning of these enzymes is essential for maintaining protein homeostasis, and our work promises to elucidate how their failure gives rise to a range of human diseases.

Courses taught

• BCH440H Protein Homeostasis
• JBB2025H Protein Crystallography

Cross-affiliations

• Department of Biochemistry, University of Toronto