Talk title: Painting Proteins: Exploring Dynamic Protein Behavior with HDX-MS
Abstract:
Hydrogen Deuterium Exchange mass spectrometry (HDX-MS) is a powerful and flexible method for probing protein interactions. In this seminar I will describe the dynamic epitope mapping and conformational characterization by HDX-MS of three distinct therapeutic targets. First, the screening of four antibodies against carbonic anhydrase IX (CA-IX), a membrane-bound anticancer target with a role in homeostasis of tumor microenvironments, will be highlighted. Our results delineated three distinct binding modes, each with its own unique therapeutic outcome. Second, we deployed HDX enabled by electrochemical reduction to screen the binding of nanobodies to the large, complex, and dynamic insulin-like growth factor receptor (IGF1R). This is a promising target for receptor-mediated delivery of antibodies across the blood brain barrier. Finally, the application of a versatile HDX platform to characterize behavior of diverse therapies emerging from NRC laboratories invoking the SARS-CoV-2 spike trimer, for the treatment of the ongoing COVID-19 pandemic will be described. This collection of projects outline the unique contribution of structural mass spectrometry to the antibody and therapeutic development pipeline, and demonstrates its applicability to probe increasingly complex protein systems.
Bio:
Dr Joey Sheff received his Ph.D. in analytical chemistry from the University of Calgary where his research focused the development of structural mass spectrometry technologies for the study of protein-based interactions in complex sample types. This was followed by a post-doc position at the National Research Council Canada, where his main role is to build, adapt, and innovate a structural mass spectrometry tool box for the study of emerging biotherapeutics. He has since transitioned to a role as an assistant Research officer in the Human Health Therapeutics department. His work focuses on enhancing structural mass spectrometry capabilities to build stronger scientific foundations for developing therapeutics and to expand the target space by accessing challenging sample types to match the continuing evolution of therapeutics. In this field, he has fostered a passion for the application of biophysical tools to probe the complex biological and therapeutic challenges, with a keen eye towards novel method development. This environment has allowed for extensive internal and external collaboration, and has furthered his interest in the development of therapeutic antibodies