Source: Interfolio F180
Ian Wilson, Ph.D.
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.
Complete List of Publications (NCBI)
Education
B.Sc., Biochemistry, University of Edinburgh, ScotlandD.Phil., Molecular Biophysics, Oxford University, England
D.Sc., Biological Sciences, Oxford University, England
Professional Experience
1975 - 1977 Junior Research Fellow, Corpus Christi College, Oxford
1977 - 1980 Research Fellow in Biochemistry, Department of Biochemistry and Molecular Biology, Harvard University
1977 - 1982 Tutor in Biochemistry, Board of Tutors in Biochemistry, Harvard University
1978 - 1982 Resident Tutor in Biochemistry, Quincy House, Harvard University
1978 - 1982 Teaching Associate in Biochemistry, Harvard Summer School
1979 - 1982 Teaching Associate in Biochemistry, Harvard Extension School
1980 - 1982 Research Associate, Department of Biochemistry and Molecular Biology, Harvard University
1982 - 1983 Assistant Member, Department of Immunology, The Scripps Research Institute
1983 - 1984 Assistant Member, Department of Molecular Biology, The Scripps Research Institute
1984 - 1990 Associate Member, Department of Molecular Biology, The Scripps Research Institute
1987 - 2017 Chair, Structure and Chemistry Affinity Group, The Scripps Research Institute
1988 - Present Professor and Course Director, The Scripps Research Institute Graduate School
1991 - 2013 Professor, Department of Molecular Biology, The Scripps Research Institute
1996 - Present Professor, The Skaggs Institute for Chemical Biology, The Scripps Research Institute
1998 - 2013 Adjunct Professor, Department of Pathology, University of California at San Diego
2009 - Present Hansen Professor of Structural Biology, The Scripps Research Institute
2013 - Present Chair and Professor, Department of Integrative Structural and Computational Biology, The Scripps Research Institute
2014 - 2020 Distinguished Adjunct Professor, ShanghaiTech University
2018 - Present Adjunct Professor, Salk Institute for Biological Studies
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 Publications
Stanfield, R. L.; Wilson, I. A.; Smider, V. V. Conservation and diversity in the ultralong third heavy-chain complementarity-determining region of bovine antibodies.. Science immunology 2016, 1, aaf7962-aaf7962.
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Xu, Q.; Shoji, M.; Shibata, S.; Naito, M.; Sato, K.; Elsliger, M. A.; Grant, J. C.; Axelrod, H. L.; Chiu, H. J.; Farr, C. L.; Jaroszewski, L.; Knuth, M. W.; Deacon, A. M.; Godzik, A.; Lesley, S. A.; Curtis, M. A.; Nakayama, K.; Wilson, I. A. A Distinct Type of Pilus from the Human Microbiome. Cell 2016, 165, 690-703.
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Impagliazzo, A.; Milder, F.; Kuipers, H.; Wagner, M. V.; 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.; Radosevic, K. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science 2015, 349, 1301-1306.
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Grover, R. K.; Zhu, X.; Nieusma, T.; Boreo, 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.; Lerner, R. A.; Jones, T. M.; Boero, I. A structurally distinct human mycoplasma protein that generically blocks antigen-antibody union.. Science (New York, N.Y.) 2014, 343, 656-661.
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Ward, A. B.; Sali, A.; Wilson, I. A. Biochemistry. Integrative structural biology. Science 2013, 339, 913-915.
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Kong, L.; Giang, E.; Nieusma, T.; Kadam, R. U.; Cogburn, K. E.; Hua, Y.; Dai, X.; Stanfield, R. L.; Burton, D. R.; Ward, A. B.; Wilson, I. A.; Law, M. Hepatitis C virus E2 envelope glycoprotein core structure.. Science (New York, N.Y.) 2013, 342, 1090-4.
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