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Membrane Transport Biophysics Section - Division of Intramural Research

Joseph A. Mindell Image

Joseph A. Mindell, M.D., Ph.D., Senior Investigator

Dr. Mindell received his B.S. degree in Molecular Biophysics and Biochemistry from Yale University in 1986. In 1994 he received his M.D. and Ph.D. degrees from the Albert Einstein College of Medicine, where he worked with Alan Finkelstein studying the structure and function of ion channels formed by diphtheria toxin. After a residency in internal medicine at Brigham and Women's Hospital, Dr. Mindell did post-doctoral work with Chris Miller at Brandeis University; there he focused on structural and functional characterization of ClC-type chloride channels using cryoelectron microscopy and other approaches. Dr. Mindell joined NINDS as an investigator in 2002. His laboratory is using a combination of structural and functional approaches to answer mechanistic questions regarding ClC channels and other anion transport proteins.

Laboratory Staff

Derek Francis, Ph.D., IRTA Fellow
Sara Lioi, Ph.D., Postdoctoral Fellow
Zhen Tao, Ph.D., Visiting Fellow
Joseph A. Mindell Staff Image

Research Interests

The Membrane Transport Biophysics Unit focuses on understanding the physical principles governing membrane-protein function. Our major model proteins are members of the ClC family of anion-transport proteins. Use a combination of biochemical and physiological approaches, we seek to understand the protein elements mediating chloride selectivity as well as those involved in regulating the passage of ions across the membrane. Recent developments, including the determination of a high-resolution structure of a bacterial ClC, have allowed us to focus our attention on particular regions of these proteins, which we explore with combinations of biochemistry, genetic mutation, and electrical recordings.

Currently, we are using fluorescence-based methods to determine the nature and magnitude of conformational changes involved in the transport mechanism of ClC-ec1. We also measure the chloride and proton fluxes through these transporters using electrical recordings in lipid bilayer membranes as a means to probe the functional behavior of these proteins.

We are also interested in other transport proteins. Bacterial genome projects continue to reveal that these so-called ‘lower’ organisms express membrane proteins which are remarkably similar to their physiologically important mammalian cousins. Furthermore, compared to their ‘higher’ counterparts, these bacterial proteins are often more chemically stable and are easier to purify in large quantities, rendering them amenable to structural analysis. We have expressed several such proteins, and are pursuing more detailed analysis of their function and architecture.

Selected Recent Publications

  • Compton ELR, Taylor EM, Mindell JA
    The 3-4 loop of an archael glutamate transporter homolog experiences ligand-induced structural changes and is essential for transport, PNAS, 2010, vol. doi/10.1073/pnas.1003046107
  • Ryan RM, Compton, ELR, Mindell JA
    Functional characterization of a Na+-dependent aspartate transporter from Pyrococcus horikoshii., Journal of Biological Chemistry, 2009, vol. 284, pp. 17540-8.
  • Osteen J and Mindell JA
    Insights into the ClC-4 transport mechanism from studies of Zn2+ inhibition., Biophysical Journal, 2008, vol. 95, pp. 4668-75.
  • Graves AR. Curran PK, Smith CL, Mindell JA
    The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes, Nature, 2008, vol. doi:10.1038/nature06907 Full Text/Abstract
  • Ryan RM and Mindell JA
    The uncoupled chloride conductance of a bacterial glutamate, Nature Structural and Molecular Biology, 2007, vol. 14, pp. 365-71. Full Text/Abstract
  • Bell SP, Curran PK, Choi S, and JA Mindell
    Site-directed fluorescence studies of a prokaryotic ClC transporter, Biochemistry, 2006, vol. 45, pp. 6773.
  • Mindell JA, Maduke M, Miller C, Grigorieff N
    Projection structure of a ClC-type Cl- channel at 6.5 angstrom resolution, Nature, 2001, vol. 409, pp. 219. Full Text/Abstract
  • Mindell JA
    Commentary: Swimming through the hydrophobic sea: New insights in protein translocation, Proc Natl Acad Sci U S A, 1998, vol. 95, pp. 4081. Full Text/Abstract

Selected Earlier Publications

Contact Information

Membrane Transport Biophysics Section, NINDS
Porter Neuroscience Research Center
Building 35, Room 3B-1014
35 Convent Drive, MSC 3701
Bethesda, MD 20892-3701

Telephone: 301-402-3473 (office), 301-435-5666 (fax)