Visitor Seminar - Prof. Stephen Michnick

11:00 - 12:00

Speaker: Professor Stephen Michnick PhD, FRSC, FRSC (UK) | Professor, Canada Research Chair in Cellular Architecture | Department of Biochemistry, University of Montreal

Title: 'Genetic and energetic landscape of protein interactomes'

Host: Stathis Megas

Abstract:

Protein-protein interaction (PPI) networks accurately map environmental perturbations to their molecular consequences in cells, but effects of genome-wide genetic variation on PPIs remain unknown. We hypothesized that PPI networks integrate genetic and environmental effects, potentially defining biochemical mechanisms underlying complex polygenic traits. In this lecture I will explain how by measuring a small number of PPIs in inbred strains of Saccharomyces cerevisiae we could detect significant variations caused by ~12,000 single-nucleotide polymorphisms (SNPs) across the genome. Unlike mRNA expression and protein abundance that are primarily affected by SNPs local (in “cis”) to a gene, PPIs are predominantly affected by SNPs far (in “trans”) to the genomic loci of the interacting proteins. However, consistent with the PPI network’s small-world characteristic, these trans-acting SNPs occur in genes encoding proteins that are close to the reporter PPIs in the PPI network. We likewise discovered SNPs in non-coding RNAs and post-transcriptional regulators (3' UTRs) with, counterintuitively, larger PPI-modulating effects than SNPs within protein-coding regions. Finally, I will discuss new findings that suggest protein-protein interaction is a major source of epistasis in genetic interaction networks.

Short Bio:

Stephen Michnick received his B. Sc. and Ph. D. from the University of Toronto with Jeremy P. Carver and did postdoctoral training at the Department of Chemistry, Harvard University with Profs. Stuart Schreiber and Martin Karplus (Nobel Prize, Chemistry, 2013). The Michnick lab studies physical principles governing the organization and properties of macromolecular assemblies in living cells, including the evolution of protein folding and protein-protein interactions. They have also developed methods to measure and manipulate the spatiotemporal dynamics and topologies of protein interaction networks, on different time and space scales and applies these methods to understand how network how environmental and genetic variation modulate cellular processes and particularly the functions of mechano-active biomolecular condensates.