Physical Chemistry Seminar: Professor Ann McDermott, Columbia University
About the Seminar
Signaling in biological systems-- Insights from NMR
Ion channels are one of the largest cell-signaling superfamilies, underlying numerous critical health related phenomena. Dynamic allosteric processes in ion channels control key aspects of signaling; spontaneous inactivation processes control the time that they remain open, which, in turn, controls the responsiveness and fidelity. Solid state NMR experiments on full length wild type channels in proteo-liposomes provide evidence for evacuation of ions from the selectivity filter during channel inactivation, and thermodynamic coupling between channel opening and ion affinity. Furthermore, these experiments have identified residues that serve as “hotspots” for allostery. We examine the conductive activated state, an intermediate of the opening process, and its conformational exchange processes.
Very high order oligomeric proteins, including amyloids, are involved in cell signaling in human health and disease. For example, the master regulator for human cell cycle, RIPK3, controls a cell death pathway involved in innate immunity. Structures of amyloid forms of RIPK3 are identified based primarily on solid-state NMR.
About the Speaker
Ann McDermott earned a B. Sc. in Chemistry from Harvey Mudd College and a Ph. D. in Chemistry from U. C. Berkeley. She carried out postgraduate work at MIT with Dr. Robert Griffin studying Nuclear Magnetic Resonance, and at the Tropical Medicine Institute of the ULB in Brussels, Belgium, studying drug design and development and has been on the faculty of Columbia University since. Her research program aims to understand the remarkable ability of proteins to catalyze chemical reactions and participate in highly specific signaling cascades. She has developed and applied magnetic resonance methods to probe the structure and flexibility of proteins. Her group investigates allosteric regulation and timing of potassium ion channels, which play crucial roles in diverse contexts, from bacteria to the human nervous system. Her research group has determined the structures and characterized the dynamics of amyloids whose formation is a critical step in cellular signaling in humans. She discovered and characterized a novel polarization (NMR signal enhancement) mechanism associated with the photochemical reactions in the photosynthetic reaction center. On the basis of this research, she is the recipient of the Pure Award in Chemistry the Eastern Analytic Symposium Award for Achievement in Magnetic Resonance and the Laukien award. She is an elected member of both the American Academy of Arts and Sciences, and the National Academy of Sciences. Her research group has been supported by the National Institutes of Health, the National Science Foundation and the Department of Energy, the Sloan Research Foundation and the Cottrell Research Foundation. She has served twice as Chair of Chemistry and as the VP for Science Inititaves at Columbia University, and serves on the Board of Trustees for Harvey Mudd College, the New York Structural Biology Center, and Math for America.