Lukas K. Tamm

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Primary Appointment

Professor and Andrew P. Somlyo Chair, Molecular Physiology and Biological Physics

Education

  • Grad Res, Biochem and Biophysics, Cornell University
  • Dipl Biol II, Biological Sciences, University of Basel
  • PhD, Biophysics, University of Basel
  • Postdoc-Res, Biophysics, Stanford University

Research Disciplines

Biochemistry, Biophysics, Cell and Developmental Biology, Infectious Diseases/Biodefense, Microbiology, Molecular Biology, Physiology, Structural Biology, Translational Science

Research Interests

Biomembrane Structure and Function; Cell Entry of Enveloped Viruses; Neurosecretion by Exocytosis; Structure of Bacterial Pathogen Membrane Proteins; 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.
We investigate the entry of several enveloped viruses into cells, including influenza virus, human immunodeficiency virus, and Ebola virus. The mechanism of membrane fusion in this process and finding viral entry inhibitors are of particular interest.
We study the mechanism of neurotransmitter release at the synapse and its regulation by calcium. We are interested in elucidating the mechanism of exocytosis in neurons and insulin secreting cells by SNARE-mediated membrane fusion and the calcium control of this process by synaptotagmin. To this end, we use life-cell microscopy and ultrafast single particle tracking. The outcomes of these studies help to better understand neurological and neurodegenerative diseases, as well as diabetes.
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. Of particular interest is to understand and control the gating of the nanopores of OmpG from E. coli. Studies on the structure, lipid, and drug interactions OprG and OprH from Pseudomonas aeruginosa will help understanding the high antibiotic resistance of this serious human pathogen.
List of Publications in Pubmed

Personal Statement

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 are studying 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 Oprâs from Ps. aeruginosa
NMR spectroscopy and drug screening

Lab website: 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., Judith M. 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).


 

Training

  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
  • Biotechnology Training Grant
  • Training in Cell and Molecular Biology
  • Training in Molecular Biophysics

Selected Publications

Yang ST, Kiessling V, Tamm LK, Line tension at lipid phase boundaries as driving force for HIV fusion peptide-mediated fusion., 2016; Nature communications. 7() 11401. PMID: 27113279 | PMCID: PMC4853434

Liang B, Tamm LK, NMR as a tool to investigate the structure, dynamics and function of membrane proteins., 2016; Nature structural & molecular biology. 23(6) 468-74. PMID: 27273629

Kucharska I, Seelheim P, Edrington T, Liang B, Tamm LK, OprG Harnesses the Dynamics of its Extracellular Loops to Transport Small Amino Acids across the Outer Membrane of Pseudomonas aeruginosa., 2015; Structure (London, England : 1993). 23(12) 2234-45. PMID: 26655471 | PMCID: PMC4699568

Yang ST, Kiessling V, Simmons JA, White JM, Tamm LK, HIV gp41-mediated membrane fusion occurs at edges of cholesterol-rich lipid domains., 2015; Nature chemical biology. 11(6) 424-31. PMID: 25915200 | PMCID: PMC4433777

Liang B, Kiessling V, Tamm LK, Prefusion structure of syntaxin-1A suggests pathway for folding into neuronal trans-SNARE complex fusion intermediate., 2013; Proceedings of the National Academy of Sciences of the United States of America. 110(48) 19384-9. PMID: 24218570 | PMCID: PMC3845119

Gregory SM, Harada E, Liang B, Delos SE, White JM, Tamm LK, Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2., 2011; Proceedings of the National Academy of Sciences of the United States of America. 108(27) 11211-6. PMID: 21690393 | PMCID: PMC3131375