NEW DATE: 08.09.2022, 17:15, UZA 2, HS 5

06.04.2022

Structural mechanisms of ion channel gating, pharmacology, and CNS immune disorders by Ryan Hibbs

The Doctoral Program Molecular Drug Targets and the Food and Pharma Lecture series are pleased to invite you to the following lecture:

 

"Structural mechanisms of ion channel gating,
pharmacology, and CNS immune disorders

by Ryan HIBBS, PhD; Associate Professor of Neuroscience and Biophysics

UT Southwestern Medical Center, Dallas, Texas, USA

 

on: Thursday, September 8, 2022, 05:15pm (17:15)

at:  UZA 2, Josef-Holaubek-Platz 2, 1090 Vienna, Lecture Hall 5 (HS 5)

Host: Margot Ernst, MedUni

 

ABSTRACT Our lab focuses on using structural and functional approaches to understand signaling by ligand-gated ion channels in the nervous system. A major emphasis is in understanding pharmacology from a structural perspective. I will present three related stories in this upcoming seminar. The first is on a peculiar subtype of the nicotinic acetylcholine receptor family. This so-called α7 nicotinic receptor is odd in that it assembles as a homomer (all other members are heteromers), it desensitizes the fastest in its family, is remarkably permeable to Ca2+, and is found both in the CNS and periphery. We used well-developed pharmacology to trap this receptor in its three conformational states and obtain structures in lipid nanodiscs by cryo-EM. The results allow us to map the gating cycle and define how this channel facilitates Ca2+ permeation. The second project focuses on the long-standing question of how general anesthetics work. We obtained structures of the GABAA receptor, the major target of many general anesthetics, with a panel of benzodiazepine and IV anesthetics. Combining the structural results with MD simulations complements decades of functional and labeling studies on how these essential drugs potentiate the activity of this inhibitory ion channel, resulting in central nervous system depression. In the final story, I will present a brand-new project on how patient-derived antibodies that attack the central nervous system cause encephalitis and seizures through antagonizing the GABAA receptor. These projects span my group’s basic science interests through to clinical applications of advances in structural methods.

RESEARCH PROFILE:  Dr. Hibbs graduated from Whitman College, a small liberal arts college in Washington State, with a combined degree in Chemistry/Biochemistry. During doctoral research at the University of California, San Diego, he studied conformational changes in an ion channel ligand binding domain under the supervision of Dr. Palmer Taylor (Department of Pharmacology). As a postdoctoral fellow, he pursued structural and functional studies of an intact, eukaryotic ligand-gated ion channel in the laboratory of Dr. Eric Gouaux (HHMI/Vollum Institute). He joined the faculty in UT Southwestern Medical Center's Departments of Neuroscience (primary) and Biophysics (secondary) in 2012. He was promoted to Associate Professor with tenure in 2019.  


Research interest: Ion channel structure-function, Membrane protein structural biology, Neuropharmacology.

 

 

Contact: Doctoral Program MolTag, Pharmaceutical Sciences; Office.moltag@univie.ac.at

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