Michael Norris

Michael Norris

Assistant Professor

BSc, University of Guelph, 2009
MSc, University of Guelph, 2011
PhD, University of Toronto/SickKids, 2017
Postdoc, Scripps Research Institute/La Jolla Institute for Immunology, 2022

Address University of Toronto
MaRS Discovery Centre, West Tower
661 University Avenue
Toronto, ON M5G 1M1
Lab Phone 416-978-3843
Office Phone 416-946-7884
Email michael.norris@utoronto.ca

Research Description

Structural Studies of Virus Assembly

Research in the Norris lab investigates the structure and molecular assembly of deadly RNA viruses, with a special emphasis on paramyxoviruses (measles virus, mumps virus, Nipah virus, parainfluenza virus) and filoviruses (Ebola virus & Marburg virus). We use structural biology (X-ray crystallography and electron cryomicroscopy [cryo-EM]), functional biochemistry, cellular biology, and basic virology to understand the molecular mechanisms driving the intricate self-assembly of these pathogenic viruses. Using this unique broad-spectrum approach, we not only provide structures to accelerate drug discovery but also generate new hypotheses to drive innovative biological discovery.

Most of these viral infections spread when new viruses “bud” from the plasma membrane of infected cells. Budding of these new virions is coordinated by viral matrix proteins, which self-assemble to form a matrix lattice at discrete assembly sites underlying the plasma membrane of infected cells. Expression of the matrix protein alone can drive budding of virus-like particles, and are themselves sufficient for initiating these virus assembly processes. During virus infection, matrix proteins also marshal other viral structural components, including surface glycoproteins and viral replication complexes, at assembly sites along the host cell membrane to yield progeny virions. For these reasons, my lab focuses on matrix proteins as the coordinators for viral assembly. We aim to elucidate the structures and molecular mechanisms driving (1) matrix protein lattice formation, (2) interactions of matrix proteins with native lipid membranes (mechanisms of curvature), (3) moonlighting roles of matrix proteins, and (4) protein-protein interactions that link viral matrix proteins to the other viral structural proteins. Ultimately, we aim to leverage this information to guide structure based drug discovery for the design of broad spectrum antivirals that inhibit the assembly process.