WALS: DeWitt Stetten Jr. Lecture- Molecular Mechanisms Underlying Glycinergic Neurotransmission​

Born and raised in India, Dr. Sudha Chakrapani came to the United States after completing her master’s degree in biomedical engineering. She received her Ph.D. in physiology and biophysics from the University at Buffalo and went on to complete postdoctoral positions at the University of Virginia and the University of Chicago. In 2010, she joined the faculty at Case Western Reserve University in Cleveland, Ohio, in the department of physiology and biophysics. LECTURE SUMMARY: Dr. Chakrapani will present her work on glycine-induced conformational changes that underlie receptor cycling between closed, open, and desensitized states. These functional transitions are modulated by various endogenous and exogenous ligands, many with interesting therapeutic potentials. She will highlight findings from her lab on some of these regulatory pathways and the potential to harness this information toward subtype-specific drug development. Glycine Receptors (GlyRs) at the inhibitory synapses in the spinal cord and brainstem are key players in regulating motor and sensory signals. Differential expression of GlyR subtype governs their widely differing physiological functions, ranging from muscle tone and respiratory rhythm to pain perception. GlyR dysfunctions are associated with epilepsy, chronic pain, addiction, and autism. Targeted regulation of specific GlyR subtypes will require a detailed understanding of their structure, function, and pharmacology. Using cryogenic electron microscopy, electrophysiology, and molecular dynamic simulations, her lab has uncovered fundamental mechanisms that underlie GlyR activation by glycine and modulation by various endogenous and exogenous ligands. Molecular insights into these regulatory pathways pave the way for subtype-specific drug development.
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