Program Director/Principal Investigator (Last, First, Middle): Tamm, Lukas K. BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Tamm, Lukas K. Harrison Distinguished Professor eRA COMMONS USER NAME (credential, e.g., agency login) lukastamm EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) Cornell University, Ithaca, NY University of Basel, Basel, Switzerland University of Basel, Basel, Switzerland Stanford, University, Stanford, California Grad Res Dipl Biol II Ph.D. Postdoc-Res 1977-78 1978 1982 1982-1984 Biochem & Biophysics Biological Sciences Biophysics Biophysics A. Personal Statement Dr. Tamm has studied lipid-protein interactions for over thirty years and membrane fusion for about twenty years. In 1984, he originated the development of supported bilayers as a new model membrane system. Dr. Tamm’s lab has used this system ever since to study interactions of peptides (including viral fusion peptides) with lipid bilayers, fusion of influenza virus particles by TIRF microscopy, the structure and dynamics of ordered lipid domains (“rafts”), and many other membrane properties. More recently, the lab has adapted the system to also measure SNARE-mediated membrane fusion reactions. In parallel, Dr. Tamm has also studied the structure and folding of membrane proteins by NMR and other techniques for many years. For example, in 2001, he described the first structure of a larger membrane protein (OmpA) determined by NMR spectroscopy. These accomplishments make him well suited to undertake the proposed studies to understand the mechanism of SNARE-mediated membrane fusion from a membrane-based structural biology vantage point. Dr. Tamm has also served as the Director of the Biophysics Graduate Program (1999-2004) and currently serves as the Director of the Center for Membrane Biology at the University of Virginia and Vice-Chair of the Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine. B. Positions and Honors: 1977-1978 Graduate Research Associate, Biochem, Cell & Mol Biology, Cornell University, Ithaca, NY. 1979-1982 Graduate Research Associate, Biocenter, Biophys Chemistry, University of Basel, Switzerland. 1982-1984 Postdoctoral Research Associate, Department of Chemistry, Stanford University, Stanford, CA 1984-1990 Junior Group Leader (Research Assistant Professor), Biocenter, Department of Biophysical Chemistry, University of Basel, Basel, Switzerland. 1990-1994 Assistant Professor, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA. 1994-2000 Associate Professor, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA. 2000-2009 Professor, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 2008-present Director, Center for Membrane Biology, University of Virginia, Charlottesville, VA 2009-present Harrison Distinguished Professor of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 2010-present Vice-Chair, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA Honors: 1977 Student Fellowship from the “Theodore Engelmann Stiftung” (Basel), Cornell University. PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): 1982 1989 1990 1990 2002 2008 Tamm, Lukas K. Post-doctoral fellowship from the Swiss National Science Foundation (NSF), Stanford University. Biophysics Prize 1989 of the German Biophysical Society “Privatdozent” of the University of Basel, Basel, Switzerland. Life and Health Insurance Medical Research Fund Award MERIT Award NIAID Faculty of 1000 Biology Editorial Boards: 1997-pres Journal of Structural Biology 2004-pres Biophysical Journal (since 2008: Associate Editor) 2005-pres Biochim Biophys Acta (Biomembranes) 2007-pres Journal of Biological Chemistry 2007-pres Protein Engineering, Design and Selection National Committees: 1993-1997 NIH, Molecular Immunology and Diagnostics (SSS-4) Special Emphasis Panel (SBIR) 1994-pres NSF, Biophysics Program, External Reviewer 1999, 2003 NICHD, Laboratory of Cell and Mol Biophysics, Intramural Review Panel 2001,2007 NIH, BBCB and BBM Study Sections, Adhoc 2001-2008 NIH, Several Special Study Sections for Members’ Conflicts 2002-2005 Council, Biophysical Society 2003 NIH Roadmap Advisory Panel “Visions for the Future of NIGMS” 2004-2008 NIH, Several Program Project Special Study Sections 2007 NIH, Membrane Protein Roadmap Mid-Course Review Panel 2009-2011 NIH, Biochemistry and Biophysics of Membranes (BBM) Study Section, Member 2011-2013 NIH, Biochemistry and Biophysics of Membranes (BBM) Study Section, Chair B. Selected peer-reviewed publications (in chronological order): Arora, A., Abildgaard, F., Bushweller, J.H., and Tamm, L.K. (2001) Structure of the outer membrane protein A transmembrane domain by NMR spectroscopy. Nature Struct. Biol. 8:334-338. Han, X., Bushweller, J.H., Cafiso, D.S. and Tamm, L.K. (2001) Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin. Nature Struct. Biol.8:715-720. Wagner, M.L. and Tamm, L.K. (2001) Reconstituted Syntaxin1A/SNAP25 interacts with negatively charged lipids as measured by lateral diffusion in planar supported bilayers. Biophys. J. 81:266-275. Tamm, L.K., Crane, J., and Kiessling, V. (2003) Membrane fusion: a structural perspective on the interplay of lipids and proteins. Curr. Op. Struct. Biol. 13:453-466. Kiessling, V. and Tamm, L.K. (2003) Measuring distances in supported bilayers by fluorescence interference contrast microscopy: Polymer supports and SNARE proteins. Biophys. J. 84:408-418. Hong, H. and Tamm, L.K. (2004) Elastic coupling of integral membrane protein stability to lipid bilayer forces. Proc. Natl. Acad. Sci. USA 101:4065-4070. Crane, J.M. and Tamm, L.K. (2004) Role of cholesterol in the formation and nature of lipid rafts in planar and spherical model membranes. Biophys. J. 86:2965-2979. Crane, J.M., Kiessling, V. and Tamm, L.K. (2005) Measuring lipid asymmetry in planar supported lipid bilayers by fluorescence interference contrast microscopy. Langmuir 21:1377-1388. Tamm, L.K. and Liang, B. (2006) NMR of membrane proteins in solution” Prog. NMR Spectrosc. 48:201-210. Kiessling, V., Crane, J.M., and Tamm L.K. (2006) Transbilayer effects of raft-like lipid domains in asymmetric planar bilayers measured by single molecule tracking. Biophys. J. 91:3313-3326; PMCID: PMC1614489. 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. Wan, C., Kiessling, V., and Tamm, L.K. (2008) Coupling of cholesterol-rich lipid phases in asymmetric bilayers. Biochemistry 47:2190-2198. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page Program Director/Principal Investigator (Last, First, Middle): Tamm, Lukas K. Murray, D.H., Tamm, L.K., and Kiessling, V. (2009) Supported double membranes. J. Struct. Biol. 168:183189. Murray, D.H. and Tamm, L.K. (2009) Clustering of syntaxin-1A in model membranes is modulated by phosphatidylinositol-4,5-bisphosphate and cholesterol. Biochemistry 48:4617-4625, PMCID: PMC2724070. Domanska, M.K. Kiessling, V., Stein, A., Fasshauer, D., and Tamm, L.K. (2009) Single vesicle millisecond fusion kinetics reveals number of SNARE complexes optimal for fast SNARE-mediated membrane fusion. J. Biol. Chem. 284:32158-32166; PMCID: PMC2797286. Ellena, J., Liang, B., Wiktor, M. Cafiso, D.S., Jahn, R., and Tamm, L.K. (2009) Dynamic structure of lipidbound synaptobrevin suggests a nucleation-propagation mechanism for trans-SNARE complex formation. Proc. Natl. Acad. Sci. USA 106:20306-20311; PMCID: PMC2787132. Kiessling, V., Domanska, M.K., Murray, D., Wan, C., Tamm, L.K. (2009) Supported Lipid Bilayers: Development and Applications in Chemical Biology. Wiley Encyclopedia of Chemical Biology, John Wiley & Sons, Hoboken, Volume 4, pp. 411-422. Liang, B., Arora, A., and Tamm, L.K. (2010) Fast-time scale dynamics of outer membrane protein A by extended model-free analysis of NMR relaxation data. (Special issue: dynamics of membrane proteins by NMR) Biochim. Biophys. Acta 1798:68-76. Lai, A.L. and Tamm, L.K. (2010) Shallow boomerang-shaped influenza hemagglutinin G13A mutant structure promotes leaky membrane fusion. J. Biol. Chem. 285:37467-37475. Domanska, M.K., Kiessling, V., and Tamm, L.K. (2010) Docking and fast fusion of synaptobrevin vesicles depends on lipid compositions of the vesicle and the acceptor SNARE complex-containing target membrane. Biophys. J. 99:2936-2946. 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. Arouri, A., Kiessling, V., Tamm, L.K., Dathe, M., and Blume, A. (2011) Morphological changes induced by the action of antimicrobial peptides on supported lipid bilayers. J. Phys. Chem. B 115:158-167. Wan, C., Kiessling, V., Cafiso, D.S., and Tamm, L.K. (2011) Partitioning of synaptotagmin I C2 domains between liquid-ordered and liquid-disordered inner leaflet lipid phases. Biochemistry 50:2478-2485. 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. Lai, A.L., Tamm, L.K., Ellena, J.F., and Cafiso, D.S. (2011) Synaptotagmin 1 modulates lipid acyl chain order in lipid bilayers by demixing phosphosphatidylserine. J. Biol. Chem. 286, 25291-25300. Murray, D. and Tamm, L.K. (2011) Molecular mechanism of cholesterol- and phosphoinositide-mediated syntaxin clustering. Biochemistry 50, 9014-9022. 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. C. Research Support ONGOING: P01 GM72694 (PI: L.K. Tamm) NIH/NIGMS Title: Structural dynamics of presynaptic membrane fusion 4/1/2005 – 6/30/2016 A program project, consisting of six projects and cores, to examine the mechanism of presynaptic membrane fusion from a structural dynamical perspective. R37 AI30557 (PI: L.K. Tamm) (MERIT AWARD) NIH/NIAID Title: Molecular mechanisms of viral membrane fusion PHS 398/2590 (Rev. 06/09) Page 9/1/1991 – 3/31/2013 Continuation Format Page Program Director/Principal Investigator (Last, First, Middle): Tamm, Lukas K. The objective of this project is to study the mechanism of membrane fusion as mediated by influenza virus hemagglutinin and other viral fusion proteins using structural and biophysical approaches. R01 GM51329 (PI: L.K. Tamm) NIH/NIGMS Title: Structure, assembly, and function of outer membrane proteins 3/1/1997 – 4/30/2013 The goal of this project is to determine structures, dynamical and the refolding of membrane proteins by solution NMR and other techniques. COMPLETED IN LAST THREE YEARS: None. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page