Welcome

Research Interests

 

Ion channel


The Hibbs lab is pursuing atomic-scale mechanisms of synaptic proteins, with a current focus on ligand-gated ion channel structure and function. We are fascinated by how these complex molecules respond to binding of a small chemical neurotransmitter by triggering the opening of an intrinsic ion conduction pathway >50 Å away. This conformational conversion allows for diffusion-limited rates of ion flux and occurs on the millisecond timescale. We further seek to probe mechanisms of ion selectivity and allosteric modulation, with a long term goal of better informing rational therapeutic design for neurological disorders and addiction. We employ a multidisciplinary approach encompassing molecular biology, protein biochemistry, pharmacology, X-ray crystallography and electrophysiology.

 

Biosketch

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.

Crystals

 

Publications

Original Articles

  1. Althoff, T.*, Hibbs, R.E.*, Banerjee, S. and Gouaux E. "X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors." Nature 2014: 512(7514):333-337. PMID: 25143115. *Equal contribution.
  2. Hattori, M.*, Hibbs, R.E.* and Gouaux, E. "A fluorescence-detection size-exclusion chromatography-based thermostability assay for membrane protein precrystallization screening." Structure 2012: 20(8):1293-9. PMID: 22884106. *Equal contribution.
  3. Hibbs, R.E. and Gouaux, E. “Principles of activation and permeation in an anion-selective Cys-loop receptor.” Nature 2011: 474(7349):54-60. PMID: 21572436
  4. Hibbs, R.E.*, Sulzenbacher, G.*, Shi, J., Talley, T.T., Conrod, S., Kem, W.R., Taylor, P., Marchot, P., Bourne, Y. “Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor.” EMBO Journal 2009: 28(19):3040-3051. *Equal contribution. PMID: 19696737
  5. Talley, T.T., Harel, M., Hibbs, R.E., Radic Z., Tomizawa, M., Casida, J.E., Taylor, P. “Atomic interactions of neonicotinoid agonists with AChBP: Molecular recognition of the distinctive electronegative pharmacophore.” Proceedings of the National Academy of Sciences 2008: 105(21)7606-7611. PMID: 18477694
  6. Taylor, P., Talley, T.T., Radic, Z., Hansen, S.B., Hibbs, R.E., Shi, J. “Structure-guided drug design: conferring selectivity among neuronal nicotinic receptor and acetylcholine-binding protein subtypes.” Biochemical Pharmacology 2007: 74(8):1164-1171. PMID: 17826748
  7. Hibbs, R.E., Radic, Z., Taylor, P., Johnson, D.A. “Influence of agonists and antagonists on the segmental motion of residues near the agonist binding pocket of the acetylcholine-binding protein.” Journal of Biological Chemistry 2006: 281(51)39708-39718. PMID: 17068341
  8. Hibbs, R.E., Johnson, D.A., Shi, J., Hansen, S.B., Taylor, P. “Structural dynamics of the a-neurotoxin-acetylcholine binding protein complex: hydrodynamic and fluorescence anisotropy decay analyses.” Biochemistry 2005 (44)16602-16611. PMID: 16342951
  9. Hibbs, R.E., Talley, T.T. and Taylor, P. “Acrylodan conjugated cysteine side chains reveal conformational state and ligand site locations of the acetylcholine binding protein.” Journal of Biological Chemistry 2004: 279(27):28483-28491. PMID: 15117947
  10. Taylor P., Hansen S.B., Talley T.T., Hibbs R.E., Radić Z. “Contemporary paradigms for cholinergic ligand design guided by biological structure.” Bioorganic and Medicinal Chemistry Letters 2004: (14)1875-1877. PMID: 15050619

Book Chapter

  1. Hibbs, R.E., Zambon, A. “Agents acting at the neuromuscular junction and autonomic ganglia.” Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th Edition. Eds. Laurence Brunton, Bruce Chabner and Bjorn Knollman. McGraw-Hill Publishing, 2011.