Simon Sharpe

Simon Sharpe obtained his BSc in Cell Biology and Biochemistry at the Memorial University of Newfoundland in 1997. After obtaining a PhD from the biochemistry department of the University of Western Ontario in 2002, he joined Robert Tycko’s group at the NIH as a postdoctoral fellow – using solid state NMR to determine the structures of peptide-antibody complex and integral membrane proteins involved in the pathogenesis of HIV-1. Dr. Sharpe joined the program in Molecular Structure and Function at The Hospital for Sick Children and the Department of Biochemistry in 2006, where his research interests include self-assembling proteins (amyloid formation in degenerative diseases, elastomeric proteins, and others), protein-membrane interactions and integral membrane proteins.

Molecular-Level Study of Macromolecular Assemblies in Human Health and Disease

The assembly of peptides and proteins into large macromolecular complexes plays an important role in normal biological processes and in the development of many disease states. The primary goal of the research program undertaken in our group is to obtain a molecular-level understanding of several macromolecular assemblies that play important roles in human health and disease. We have used an approach based on solid-state NMR (SSNMR), which has emerged as the technique of choice for investigating the structural and dynamic properties of amyloid fibrils, integral membrane proteins, and other large macromolecular complexes. In addition to providing high-resolution structural data on protein assemblies, this method also permits direct observation of protein-membrane interactions.

To complement the structural information provided by SSNMR, we use a broad range of other biophysical techniques, including solution NMR, transmission electron microscopy (TEM), fluorescence spectroscopy, Fourier-transform infrared spectroscopy (FTIR), and small angle X-ray scattering (SAXS), among others. We are using this multidisciplinary approach to address questions in three key areas: (1) The molecular basis for amyloid assembly and cytotoxicity in model peptides, prions, and in systemic amyloidosis caused by misfolding of apolipoproteins; (2) The assembly and structure of elastomeric proteins – understanding the functional properties of potential biomaterials; and (3) Antagonism of host cell immune response by viral membrane proteins. Our goal in each case is to obtain details of the molecular structure and intermolecular interactions that are important to the biological system. In addition to enhancing fundamental understanding of protein folding, assembly and membrane interactions, our results will provide insight into the mechanisms of human disease, with the ultimate goal of identifying new areas for therapeutic intervention.

Appointments, Cross Affiliations, Memberships

Hospital for Sick Children - Associate Chief, Research Training Centre
Hospital for Sick Children - Senior Scientist, Molecular Medicine

Courses Taught

BCH374Y1 Research Project in Biochemistry
JBB2026H Protein Structure, Folding, and Design
BCH473Y Advanced Research Project in Biochemistry
BCH425H Structural Biology: Principles and Practice
BCH2125 Structure and Dynamics of Biomacromolecules Using Solid State NMR Spectroscopy

Awards and Distinctions

2006-2016 — Canada Research Chair  
2010 — Ontario Early Researcher Award