Grant: Discovery Grants Program - Individual

Our group develops novel techniques for electrospray ionization (ESI) mass spectrometry (MS) and molecular dynamics (MD) simulations. We apply these tools to unravel the biophysical foundations of protein structure, dynamics, and function. Our work has impacted labs around the world. Research and service leadership benchmarks include major recognitions such as FRSC, CSC Aroca Award, and Distinguished Univ. Prof. Our long-term vision is to characterize protein dynamics with atomic resolution, and to decipher the noncovalent interaction networks that mediate biomolecular self-assembly. The current DG works toward this vision by pursuing three short-term objectives: 1. Elucidating Protein Dynamics in Solution. Hydrogen/deuterium exchange (HDX)/MS is widely used for probing protein dynamics, despite major uncertainties regarding data interpretation. We will develop a greatly improved understanding of HDX protection effects, providing an atomistic readout of protein motions. A brand new direction is the use of HDX/MS to uncover protein dynamics that mediate biological electron transport during respiration and photosynthesis. 2. Deciphering Protein Oxidation & Aggregation in Solution. Unfolding experiments are often plagued by degradation artifacts, precluding the measurement of key thermodynamic parameters. We will develop strategies for conducting such experiments in an artifact-free fashion by suppressing spurious oxidation. We will also unravel the oxidation- and lipid-induced structural changes that turn cytochrome c into a peroxidase, a topic of crucial importance for apoptosis (programed cell death). In addition, we will uncover the mechanisms whereby monoclonal antibodies aggregate, paving the way toward more robust cancer therapeutics. 3. Understanding ESI Mechanisms and Gas Phase Biomolecules. Our recent work has greatly advanced the understanding of gas phase ion formation during ESI. However, those activities were limited to "late" nanodroplets. The current DG takes a more holistic approach by pioneering experimental and MD strategies that capture the entire ESI process, from the Taylor cone to desolvated ions. This work will be transformative by revealing under what conditions (and to what extent) ESI preserves native-like protein structures in the absence of solvent. HQP Training, EDI, and Impact. Our lab provides a mentoring environment that is open, friendly, inclusive, and equitable. We will boost diversity by recruiting individuals from underrepresented groups. Our HQP graduate with exceptional skills, high-profile publications, major awards, and prestigious scholarships. Becoming part of "Team Konermann" empowers HQP by offering a springboard for prosperous careers in industry and academia. Our research and training will benefit people in Canada and beyond, by opening novel avenues toward bio-inspired nano-devices and innovative therapeutic approaches.