Faculty

Randy Stockbridge

Assistant Professor of Biophysics; Molecular, Cellular, and Developmental Biology

Ph.D., University of North Carolina - Chapel Hill

Research Focus: Structure/function of membrane proteins, microbial fluoride resistance

Phone: 734.764.1146
E-mail: stockbr@umich.edu

Membrane transport proteins – channels and energy-coupled pumps – are the molecular gatekeepers of the cell.  For microbes afloat in a hostile environment, these proteins import vital nutrients and export dangerous toxins.  My lab is currently focused on understanding the export of F- anion, an inhibitor of glycolysis and protein synthesis that bacteria, archaea, unicellular eukaryotes, and plants have confronted in their environmental milieu over evolutionary time. 

Specific F- export isn’t an easy task since the ion’s radius only differs by half an Angstrom from that of the world’s most abundant aqueous ion, Cl-.   Two different membrane protein families have evolved to accomplish it: the Fluc family of fluoride channels, and the CLCF family of F-/H+ antiporters. My laboratory is investigating the molecular mechanism of both classes of protein, with a focus on the molecular interactions that stabilize a charge as it transits the greasy, hydrophobic span of the bilayer, the thermodynamics and kinetics of conformational changes involved in transport, the energetics of substrate coupling in the transporter family, and protein-protein interactions between the Fluc channels and engineered proteins that block F- current.

To this end, my lab employs a breadth of biochemical and biophysical techniques, including electrophysiology, membrane protein biochemistry, x-ray crystallography, and macromolecular NMR.

 

Awards

2014-2019
K99/R00 Pathway to Independence Award; National Institute of General Medical Sciences

 


Representative Publications

  1. Stockbridge RB, Kolmakova-Partensky L, Shane T, Koide A, Koide S, Miller C, Newstead S. (2015). Crystal structures of a dual-topology, double-barrelled fluoride ion channel. Nature. 525:548-551.

  2. Stockbridge RB, Robertson JL, Kolmakova-Partensky L, Miller C.  (2013). A family of fluoride-specific ion channels with dual-topology architecture.  eLife 2013;2:e01084.

  3. Stockbridge RB, Lim H-H, Otten R, Williams C, Shane T, Weinberg Z, Miller C. (2012). Fluoride resistance and transport by riboswitch-controlled CLC antiporters. Proc. Natl. Acad. Sci. U.S.A. 109: 15289-15294.

  4. Ji C, Stockbridge RB, Miller C.  (2014). Bacterial fluoride resistance, Fluc channels, and the weak acid accumulation effect.  J. Gen. Physiol.  144:257-261.

  5. Baker JL, Sudarsan N, Weinberg Z, Roth A, Stockbridge RB, Breaker RR. (2012). Widespread genetic switches and toxicity resistance proteins for fluoride. Science. 335: 233-235.

  6. Stockbridge RB, Koide A, Miller C, Koide S.  (2014). Proof of dual–topology architecture of Fluc F- channels with monobody blockers.  Nat. Commun.  5:5120.

 

Presentations

  1. Crystal structures of a double-barelled fluoride channel. Membrane Biophysics Subgroup 2016 Symposium, Biophysical Society Meeting.  Los Angeles, CA.  Feb. 27, 2016.

  2. Crystal structure of a dual topology, double-barrelled fluoride channel.  NCCS TransCure Ion Channel Women Scientists Symposium.  Bern, Switzerland.  Sept. 4, 2015.

  3. Crystal structure of a dual-topology fluoride channel.  Mechanisms of Membrane Transport Gordon Research Conference.  Lewiston, ME.  July 3, 2015.

  4. Monobody block of a Fluc F- channel: function and structure.  Ion Channels Gordon Research Conference.  South Hadley, MA.  July 7, 2014.

  5. Dual topology architecture of fluoride-selective ion channels.  Ligand Gating and Molecular Recognition Gordon Research Conference.  Ventura, CA.  March 26, 2014.

  6. A dimeric dual-topology microbial fluoride channel.  Biophysical Society Annual Meeting Platform.  San Francisco, CA.  February 18, 2014.

  7. Fluoride transport in a strange subclass of CLCs.  Ion Channels Gordon Research Conference.  South Hadley, MA.  July 11, 2012.

 

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