Lukas K. Tamm

Education

  • Postdoc-Res, Stanford, University, Stanford, California
  • Grad Res, Cornell University, Ithaca, NY
  • Dipl Biol II, University of Basel, Basel, Switzerland
  • PhD, University of Basel, Basel, Switzerland

Primary Appointment

  • Professor, Molecular Physiology and Biological Physics

Contact

Research Interest(s)

Biomembrane Structure and Function; Membrane Fusion in Viral Cell Entry and Exocytosis; Lipid-Protein Interactions

Research Description

Our lab studies the structure and function of several membrane proteins of clinical importance in their natural membrane environment. We are also interested in the roles that membrane lipids play in the regulation of these proteins. Membrane proteins that play key roles in infectious and neurological diseases are of particular interest in our laboratory.

Membrane Fusion in Viral Infection We investigate the entry of several viruses into cells, including:

  • Influenza virus
  • Human immunodeficiency virus
  • Ebola virus

    Membrane Fusion in Neurotransmitter Release

    We study the mechanism of neurotransmitter release at the synapse and its regulation by calcium.

  • Synaptic exocytosis by SNARE-mediated membrane fusion
  • Calcium control by synaptotagmin
  • Ultrafast single particle tracking by live-cell microscopy
  • Relation to neurological and neurodegenerative diseases

    Structure-Function-Dynamics-Antibiotic Interactions of Membrane Channels from Pathogenic Bacteria Gram-negative bacteria like E. coli and Pseudomonas are enveloped by two membranes. We study channels of the outer membranes of these bacteria and their contribution to antibiotic resistance.

  • Gating of OmpA and OmpG from E. coli
  • Structure, lipid, and drug interactions of Opr’s from Ps. aeruginosa
  • NMR spectroscopy and drug screening

    Lab website: href="http://pages.shanti.virginia.edu/Tamm_Lab/">http://pages.shanti.virginia.edu/Tamm_Lab/

    Selected recent publications: Hong, H., Szabo, G., and Tamm, L.K. (2006) Electrostatic side-chain couplings in the gating of the OmpA ion channel suggest a mechanism for pore opening. Nature Chem. Biol. 11:627-635. Liang, B. and Tamm, L.K. (2007) Structure of outer membrane protein G by solution NMR. Proc. Natl. Acad. Sci. USA 104:16140-16145. Ellena, J., Liang, B., Wiktor, M. Cafiso, D.S., Jahn, R., and Tamm, L.K. (2009) Dynamic structure of lipid-bound synaptobrevin suggests a nucleation-propagation mechanism for trans-SNARE complex formation. Proc. Natl. Acad. Sci. USA 106:20306-20311. Kiessling, V., Domanska, M.K., and Tamm, L.K. (2010) Single SNARE-mediated vesicle fusion observed in vitro by polarized TIRFM. Biophys. J. 99:4047-4055. Gregory, S.M., Harada,E., Liang, B., Delos, S.E., White, J.M. and Tamm, L.K. (2011) Structure and function of the complete internal fusion loop from Ebolavirus GP2. Proc. Natl. Acad. Sci. USA 108, 11211-11216. Edrington, T.C., Kintz, E., Goldberg, J.B., and Tamm, L.K. (2011) Structural basis for the interaction of lipopolysaccharide with the outer membrane protein OprH from Pseudomonas aeruginosa. J. Biol. Chem. 286, 39211-39223. Lai, A.L. Moorthy, A,E., Li, Y, and Tamm, L.K. (2012) Fusion activity of HIV gp41 fusion domain is related to its secondary structure and depth of membrane insertion in a cholesterol-dependent fashion. J. Mol. Biol. 418, 3-15 (on cover).

    Selected Publications

    • Gregory S, Larsson P, Nelson E, Kasson P, White J, Tamm L. Ebolavirus Entry Requires a Compact Hydrophobic Fist at the Tip of the Fusion Loop. Journal of virology. 2014. PMID: 24696482 | PMCID: PMC4054381
    • Tamm L, Lee J, Liang B. Capturing Glimpses of an Elusive HIV Gp41 Prehairpin Fusion Intermediate. Structure (London, England : 1993). 2014;22(9): 1225-6. PMID: 25185826
    • Lateral membrane diffusion corralled. Biophysical journal. 2013;104(7): 1399-400. PMID: 23561515 | PMCID: PMC3617411
    • Liang B, Kiessling V, Tamm L. Prefusion structure of syntaxin-1A suggests pathway for folding into neuronal trans-SNARE complex fusion intermediate. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(48): 19384-9. PMID: 24218570 | PMCID: PMC3845119
    • Lai A, Moorthy A, Li Y, Tamm L. Fusion activity of HIV gp41 fusion domain is related to its secondary structure and depth of membrane insertion in a cholesterol-dependent fashion. Journal of molecular biology. 2012;418(1): 3-15. PMID: 22343048
    • Edrington T, Kintz E, Goldberg J, Tamm L. Structural basis for the interaction of lipopolysaccharide with outer membrane protein H (OprH) from Pseudomonas aeruginosa. The Journal of biological chemistry. 2011;286(45): 39211-23. PMID: 21865172 | PMCID: PMC3234746
    • Gregory S, Harada E, Liang B, Delos S, White J, Tamm L. Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(27): 11211-6. PMID: 21690393 | PMCID: PMC3131375
    • Lai A, Tamm L, Ellena J, Cafiso D. Synaptotagmin 1 modulates lipid acyl chain order in lipid bilayers by demixing phosphatidylserine. The Journal of biological chemistry. 2011;286(28): 25291-300. PMID: 21610074 | PMCID: PMC3137100
    • Murray D, Tamm L. Molecular mechanism of cholesterol- and polyphosphoinositide-mediated syntaxin clustering. Biochemistry. 2011;50(42): 9014-22. PMID: 21916482 | PMCID: PMC3199950
    • Wan C, Kiessling V, Cafiso D, Tamm L. Partitioning of synaptotagmin I C2 domains between liquid-ordered and liquid-disordered inner leaflet lipid phases. Biochemistry. 2011;50(13): 2478-85. PMID: 21322640 | PMCID: PMC3094915
    • Domanska M, Kiessling V, Tamm L. Docking and fast fusion of synaptobrevin vesicles depends on the lipid compositions of the vesicle and the acceptor SNARE complex-containing target membrane. Biophysical journal. 2010;99(9): 2936-46. PMID: 21044591 | PMCID: PMC2965956
    • Domanska M, Kiessling V, Stein A, Fasshauer D, Tamm L. Single vesicle millisecond fusion kinetics reveals number of SNARE complexes optimal for fast SNARE-mediated membrane fusion. The Journal of biological chemistry. 2009;284(46): 32158-66. PMID: 19759010 | PMCID: PMC2797286
    • Ellena J, Liang B, Wiktor M, Stein A, Cafiso D, Jahn R, Tamm L. Dynamic structure of lipid-bound synaptobrevin suggests a nucleation-propagation mechanism for trans-SNARE complex formation. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(48): 20306-11. PMID: 19918058 | PMCID: PMC2787132
    • Li Y, Tamm L. Structure and plasticity of the human immunodeficiency virus gp41 fusion domain in lipid micelles and bilayers. Biophysical journal. 2007;93(3): 876-85. PMID: 17513369 | PMCID: PMC1913135
    • Tamm L, Lai A, Li Y. Combined NMR and EPR spectroscopy to determine structures of viral fusion domains in membranes. Biochimica et biophysica acta. 2007;1768(12): 3052-60. PMID: 17963720 | PMCID: PMC2213455
    • Cierpicki T, Liang B, Tamm L, Bushweller J. Increasing the accuracy of solution NMR structures of membrane proteins by application of residual dipolar couplings. High-resolution structure of outer membrane protein A. Journal of the American Chemical Society. 2006;128(21): 6947-51. PMID: 16719475 | PMCID: PMC2527590
    • Kiessling V, Crane J, Tamm L. Transbilayer effects of raft-like lipid domains in asymmetric planar bilayers measured by single molecule tracking. Biophysical journal. 2006;91(9): 3313-26. PMID: 16905614 | PMCID: PMC1614489
    • Lai A, Park H, White J, Tamm L. Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity. The Journal of biological chemistry. 2006;281(9): 5760-70. PMID: 16407195
    • Liang B, Bushweller J, Tamm L. Site-directed parallel spin-labeling and paramagnetic relaxation enhancement in structure determination of membrane proteins by solution NMR spectroscopy. Journal of the American Chemical Society. 2006;128(13): 4389-97. PMID: 16569016 | PMCID: PMC3199951