Ian Wilson, PhD
Scripps Research Joint Appointments
Research Focus
Structural Studies of the Immune System, Viral Pathogens, and Vaccine Design
Immunologic recognition of microbial pathogens is fundamental for fighting infectious disease. Our major goal is to understand the interaction and neutralization of foreign antigens by the immune system through high-resolution x-ray structural studies of antibodies, Variable Lymphocyte Rectors (VLRs) and antigens in the humoral system, T-cell receptor complexes with MHC class I and class II in the cellular system, and through pattern recognition receptors, such as TLRs, in the innate immune system.
Over 250 crystal structures of monoclonal Fab fragments and complexes with a variety of antigens, such as peptides, steroids, cocaine, and proteins, including HIV-1, gp120 and gp41, have led to significant insights into antibody-antigen recognition, virus neutralization, and vaccine design for HIV-1. In addition, catalytic or fluorescent antibodies, many of which carry out disfavored reactions or for which no natural enzymes exist, or have interesting physico-chemical properties have given us insight into a myriad of uses as artificial catalysts or as biosensors. The T-cell receptor in complex with pMHC has revealed how peptide antigens can be recognized in the context of the MHC molecule. Many other key molecules in cellular immunology are being studied, such as non-classical or MHC homologues: for example, CD1 binds lipid, glycolipid, and lipopeptide antigens from the cell walls of microbial pathogens and the NK family of receptors recognizes classical as well as distant MHC homologues. Studies on other pattern recognition receptors, include peptidoglycan recognition protein (PGRP), TREM-1, Toll-like receptors (TLR) have revealed how unique pathogen-associated molecules are recognized by the immune system.
Much of our recent work is focused on HIV-1 and influenza viruses. The 1918 flu, which killed 20-40 million people worldwide, is being investigated through structural and binding studies of the 1918 viral proteins, such as the hemagglutinin (HA) and neuraminidase, as well as other the viral proteins. The avian H5N1 and swine H1N1 influenza virus HA structures have been determined as well as mutations that enhance binding to human receptors that may allow the virus to cross the species barrier into humans and be transmissible. We have also determined structures of almost all of the rare, broadly neutralizing antibodies against the HIV-1 envelope proteins, gp120 and gp41, in order to elucidate the sites of vulnerability that can be used for HIV-1 vaccine design. A very exciting project on broadly neutralizing antibodies with influenza virus has revealed novel epitopes that are of great value for structure-assisted vaccine development. We have defined a broadly neutralizing epitope in all group 1 influenza subtypes and are working on other antibodies that recognize group 2 as well as those that cross all subtypes. Other flu projects are associated with the nucleoproteins, polymerases and neuraminidases in order to understand how influenza replicates.
I also directed the Joint Center for Structural Genomics (2000-2016) that pioneers new high throughput methodologies and technologies for protein production, structure determination and functional analysis in order to investigate the Expanding Protein Universe and the human gut microbiome and other high-value targets in the regulation of stem cells and T cells.
Education
B.Sc., Biochemistry, University of Edinburgh, ScotlandD.Phil., Molecular Biophysics, Oxford University, England
D.Sc., Biological Sciences, Oxford University, England
Awards & Professional Activities
Awards and Honors: The Newcomb Cleveland Prize for an Outstanding Contribution to Science, AAAS (1997), Peter Gorer Lectureship, British Society for Immunology (2000), Fellow, Royal Society of London (2000), Member, American Academy of Arts and Sciences (2002), D.Sc. (hon.), University of St. Andrews (2007), Corresponding Fellow, Royal Society of Edinburgh (2008), Honorary Fellowship, Corpus Christi College, Oxford (2009), The 1st Bernie Gilula Award for Faculty Excellence, Graduate Program, TSRI (2010), The 2nd Outstanding Mentor Award, Society of Fellows, TSRI (2012), Foreign Associate, National Academy of Sciences (2016), Fellow, American Academy of Microbiology (2016)Activities: Associate Editor, Journal of Molecular Biology (1994-2013), Associate Editor, Immunity (1997-present), Board of Reviewing Editors and Statistical Board of Reviewing Editors, Science (1997-present), Career Awards Committee, Burroughs Wellcome (1997–2005), Advisory Editor, Journal of Experimental Medicine (1998-present), Study Section, NIH BBCB (1998-2002), Scientific Advisory Board, Keystone Symposia (2000-present), Director of the NIGMS Joint Center for Structural Genomics (2000-2016), Vaccine Research Working Group (AVRWG), NIAID AIDS (2004-2008), Board of Directors, Keystone Symposia (2008-present), International Scientific Advisory Board (ISAB), Academia Sinica, Taipei, Taiwan (2015-present), Advisory Board, SCOPe (2015-present).
Selected References
Wilson IA, Skehel JJ, Wiley DC. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution. (1981) Nature 289:366-73.
Stanfield, R.L., Fieser, T.M., Lerner, R.A., and Wilson, I.A. (1990). Crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 Å. Science 248, 712-719.
Fremont, D.H., Matsumura, M., Stura, E.A., Peterson, P.A., and Wilson, I.A. (1992). Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science 257, 919-927.
Garcia, K.C., Degano, M., Stanfield, R.L., Brunmark, A., Jackson, M.R., Peterson, P.A., Teyton, L., and Wilson, I.A. (1996). An αβ T cell receptor structure at 2.5 Å and its orientation in the TCR-MHC complex. Science 274, 209-219.
Livnah, O., Stura, E.A., Johnson, D.L., Middleton, S.A., Mulcahy, L.S., Wrighton, N.C., Dower, W.J., Jolliffe, L.K., and Wilson, I.A. (1996). Functional mimicry of a protein hormone by a peptide agonist: the EPO receptor complex at 2.8 Å. Science 273, 464-471.
Heine, A., Stura, E.A., Yli-Kauhaluoma, J.T., Gao, C., Deng, Q., Beno, B.R., Houk, K.N., Janda, K.D., and Wilson, I.A. (1998). An antibody exo Diels-Alderase inhibitor complex at 1.95 angstrom resolution. Science 279, 1934-1940.
Calarese, D.A., Scanlan, C.N., Zwick, M.B., Deechongkit, S., Mimura, Y., Kunert, R., Zhu, P., Wormald, M.R., Stanfield, R.L., Roux, K.H., Kelly, J.W., Rudd, P.M., Dwek, R.A., Katinger, H., Burton, D.R., and Wilson, I.A. (2003). Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 300, 2065-2071.
Stevens, J., Corper, A.L., Basler, C.F., Taubenberger, J.K., Palese, P., and Wilson, I.A. (2004). Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 303, 1866-1870.
Stanfield, R.L., Dooley, H., Flajnik, M.F., and Wilson, I.A. (2004). Crystal structure of a shark single-domain antibody V region in complex with lysozyme. Science 305, 1770-1773.
Choe J., Kelker M.S., Wilson I.A. (2005) Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science 309:581-585.
Stevens J., Blixt O., Tumpey T.M., Taubenberger J.K., Paulson J.C., Wilson I.A. (2006) Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312:404-410.
Han, B.W., Herrin, B.R., Cooper, M.D., Wilson, I.A. (2008) Antigen recognition by variable lymphocyte receptors. Science 321:1834-1837.
Zhang Y, Thiele I, Weekes D, Li Z, Jaroszewski L, Ginalski K, Deacon AM, Wooley J, Lesley SA, Wilson IA, Palsson B, Osterman A, Godzik A. (2009) Three-dimensional structural view of the central metabolic network of Thermotoga maritima. Science 325:1544-9.
Ekiert, D. C., Bhabha, G., Elsliger, M. A., Friesen, R. H., Jongeneelen, M., Throsby, M., Goudsmit, J., and Wilson, I. A. (2009) Antibody recognition of a highly conserved influenza virus epitope. Science 324:246-251.
Elsliger MA, Deacon AM, Godzik A, Lesley SA, Wooley J, Wüthrich K, Wilson IA. (2010) The JCSG high-throughput structural biology pipeline. Acta Crystallogr, Sect. F Struct. Biol. Cryst. Commun. 66:1137-42
Xu, R., Ekiert, D. C., Krause, J. C., Hai, R., Crowe, J. E., Jr., and Wilson, I. A. (2010) Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus. Science 328:357-360.
Verdino, P., Witherden, D. A., Havran, W. L., and Wilson, I. A. (2010) The molecular interaction of CAR and JAML recruits the central cell signal transducer PI3K. Science 329:1210-1214.
Fleishman, S.J., Whitehead, T.A., Ekiert, D.C., Dreyfus, C., Corn, J.E., Strauch, E.M., Wilson, I.A., and Baker, D. (2011). Computational design of proteins targeting the conserved stem region of influenza hemagglutinin. Science 332, 816-821
Pejchal, R., Doores, K.J., Walker, L.M., Khayat, R., Huang, P.S., Wang, S.K., Stanfield, R.L., Julien, J.P., Ramos, A., Crispin, M., Depetris, R., Katpally, U., Marozsan, A., Cupo, A., Maloveste, S., Liu, Y., McBride, R., Ito, Y., Sanders, R.W., Ogohara, C., Paulson, J.C., Feizi, T., Scanlan, C.N., Wong, C.H., Moore, J.P., Olson, W.C., Ward, A.B., Poignard, P., Schief, W.R., Burton, D.R., and Wilson, I.A. (2011). A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334, 1097-1103.
Yoon, S.I., Kurnasov, O., Natarajan, V., Hong, M., Gudkov, A.V., Osterman, A.L., and Wilson, I.A. (2012). Structural basis of TLR5-flagellin recognition and signaling. Science 335, 859-864.
Ekiert, D.C., Kashyap, A.K., Steel, J., Rubrum, A., Bhabha, G., Khayat, R., Lee, J.H., Dillon, M.A., O'Neil, R.E., Faynboym, A.M., Horowitz, M., Horowitz, L., Ward, A.B., Palese, P., Webby, R., Lerner, R.A., Bhatt, R.R., and Wilson, I.A. (2012). Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 489, 526-532.
Julien, J.P., Cupo, A., Sok, D., Stanfield, R.L., Lyumkis, D., Deller, M.C., Klasse, P.J., Burton, D.R., Sanders, R.W., Moore, J.P., Ward, A.B., and Wilson, I.A. (2013). Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342, 1477-1483.
Lyumkis, D., Julien, J.P., de Val, N., Cupo, A., Potter, C.S., Klasse, P.J., Burton, D.R., Sanders, R.W., Moore, J.P., Carragher, B., Wilson, I.A., and Ward, A.B. (2013). Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 342, 1484-1490
Kong L, Giang E, Nieusma T, Kadam RU, Cogburn KE, Hua Y, Dai X, Stanfield RL, Burton DR, Ward AB, Wilson IA, Law M. (2013) Hepatitis C virus E2 envelope glycoprotein core structure. Science 342:1090-4.
Ward, A.B., Sali, A., and Wilson, I.A. (2013). Biochemistry. Integrative structural biology. Science 339, 913-915.
Grover, R.K., Zhu, X., Nieusma, T., Jones, T., Boero, I., MacLeod, A.S., Mark, A., Niessen, S., Kim, H.J., Kong, L., Assad-Garcia, N., Kwon, K., Chesi, M., Smider, V.V., Salomon, D.R., Jelinek, D.F., Kyle, R.A., Pyles, R.B., Glass, J.I., Ward, A.B., Wilson, I.A., and Lerner, R.A. (2014). A structurally distinct human mycoplasma protein that generically blocks antigen-antibody union. Science 343, 656-661
Impagliazzo, A.* Milder, F., Kuipers, H., Wagner, M., Zhu, X., Hoffman, R.M., van Meersbergen, R., Huizingh, J., Wanningen, P., Verspuij, J., de Man, M., Ding, Z., Apetri, A., Kukrer, B., Sneekes-Vriese, E., Tomkiewicz, D., Laursen, N.S., Lee, P.S., Zakrzewska, A., Dekking, L., Tolboom, J., Tettero, L., van Meerten, S., Yu, W., Koudstaal, W., Goudsmit, J., Ward, A.B., Meijberg, W., Wilson, I.A.*, and Radosevic, K. (2015). A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science 349, 1301-1306.
Xu Q, Shoji M, Shibata S, Naito M, Sato K, Elsliger MA, Grant JC, Axelrod HL, Chiu HJ, Farr CL, Jaroszewski L, Knuth MW, Deacon AM, Godzik A, Lesley SA, Curtis MA, Nakayama K, Wilson IA. (2016) A Distinct Type of Pilus from the Human Microbiome. Cell 165:690-703.
Stanfield, R.L., and Wilson, I.A., and Smider, V.V. (2016). Conservation and diversity in the ultralong third heavy-chain complementarity-determining region of bovine antibodies. Sci Immunol 1, aaf7962.