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The Scripps Research Institute Scientific Report T HE S CRIPPS R ESEARCH I NSTITUTE Scientific Report 2006 ON THE COVER: “Click” chemistry refers to the development and use of highly reliable chemical reactions to make molecules that perform a desired function. The most successful click reaction is the copper-catalyzed azide-alkyne cycloaddition (CuAAC) process, an abstract representation of which is shown here. Blue (azide) and red (alkyne) components are efficiently joined by spherical copper ions to give pentagonal 1,4-triazoles. Surrounding the large triazole motif in the foreground are energy diagrams high- lighting favorable aspects of the reaction, and its biological applications are represented by icosahedral virus particles. The brick-like mosaic tying the entire image together suggests both the highly modular nature of the CuAAC reaction and its use- fullness in the creation of functional small molecules, polymers, and materials. The overall theme celebrates the importance of connections: in chemistry, as in life, while individuals may be unique and pleasing, it is when they “click” together that true art is created. Painting by Yeon-Hee Lim, Ph.D., research associate in the laboratory of M.G. Finn, Ph.D., Department of Chemistry. VOLUME 32 THE SCRIPPS RESEARCH INSTITUTE SCIENTIFIC REPORT PRESIDENT’S INTRODUCTION 5 INFECTOLOGY Staff and Fellows 355 CALIFORNIA Chairman’s Overview 355 Investigators’ Reports 356 THE SKAGGS INSTITUTE FOR CHEMICAL TRANSLATIONAL RESEARCH INSTITUTE BIOLOGY Staff and Fellows 363 Staff and Fellows 11 Chairman’s Overview 364 Director’s Overview 13 Investigators’ Reports 365 Investigator’s Reports 15 CELL BIOLOGY Staff and Fellows 19 A WARDS, EDUCATION, CENTERS AND Chairman’s Overview 22 INSTITUTES, AND ORGANIZATIONS Investigators’ Reports 24 Staff Awards and Activities 373 CHEMISTRY Kellogg School of Science and Technology 377 Staff and Fellows 63 Chairman’s Overview 67 Center for Integrative Molecular Biosciences 382 Investigators’ Reports 69 The Harold L. Dorris Neurological Research Center 383 IMMUNOLOGY Helen L. Dorris Child and Adolescent 384 Staff and Fellows 99 Neuro-Psychiatric Disorder Institute Chairman’s Overview 102 The Institute for Childhood and Neglected Diseases 384 Investigators’ Reports 104 Society of Fellows 386 MOLECULAR BIOLOGY Staff and Fellows 153 Author Index 387 Chairman’s Overview 158 Subject Index 395 Investigators’ Reports 160 MOLECULAR AND EXPERIMENTAL MEDICINE Staff and Fellows 239 Chairman’s Overview 242 Investigators’ Reports 245 MOLECULAR AND INTEGRATIVE NEUROSCIENCES Staff and Fellows 287 Chairman’s Overview 289 Investigators’ Reports 291 NEUROBIOLOGY Staff and Fellows 327 Chairman’s Overview 328 Investigators’ Reports 330 FLORIDA BIOCHEMISTRY Staff and Fellows 339 Chairman’s Overview 340 Investigators’ Reports 340 Vessels of a human retina (macula). The image shows the avascular zone of the fovea. Image provided by Edith CANCER BIOLOGY Aguilar de Diaz, M.D., Scientific Associate, Matthew Ritter, Staff and Fellows 350 Ph.D., Research Associate, and Martin Friedlander, M.D., Ph.D., Chairman’s Overview 350 Professor. Work done in the Friedlander laboratory in the Investigators’ Reports 351 Department of Cell Biology. Published by TSRI Press®. © Copyright 2006, The Scripps Research Institute. All rights reserved. 2 THE SCRIPPS RESEARCH INSTITUTE 2006 BOARD OF TRUSTEES John J. Moores Alexander W. Dreyfoos Chair of the Board, Scripps Research Private Investor Former Chairman, Board of Regents of the University of California Chairman, Raymond F. Kravis Center for the Performing Arts Chairman, JMI and San Diego Padres Charles C. Edwards, M.D. Chair, Board of Trustees, The Carter Center Former Director, Food and Drug Administration Warren Beatty Former President, Scripps Clinic and Research Foundation President, Mulholland Productions Incorporated Richard J. Elkus, Jr. Vincent E. Benstead Director, KLA-Tencor, Lam Research, Virage Logic Former Partner, PricewaterhouseCoopers Member, Board of Trustees, Palo Alto Medical Foundation Mrs. William McCormick Blair, Jr. Marjorie Fink Vice President, Albert and Mary Lasker Foundation Philanthropist J. Gary Burkhead Phillip Frost, M.D. Retired, Vice-Chairman, Fidelity Investments Chairman and Chief Executive Officer, IVAX Corporation Gary N. Coburn Louis L. Gonda Retired Senior Managing Director, Putnam Investments Chairman and Chief Executive Officer, Lexington Commercial Holdings Chairman, Lexington Ventures, L.L.C. Gerald Cohn Chairman, Lexington Realty, L.L.C. Retired Executive, Private Investor Paul L. Herrling, Ph.D. George H. Conrades Head, Corporate Research, Novartis International AG Chairman and Chief Executive Officer, Akamai Technologies, Inc. Lawrence C. Horowitz, M.D. J. Michael Cook President and Managing General Partner Retired Chairman and Chief Executive Officer, Deloitte + Touche Selby Lane Enterprises II, L.L.C. Rod Dammeyer Thomas H. Insley President, CAC, L.L.C. Vice President and Chief Financial Officer, SkinMedica, Inc. John G. Davies, Esq. Richard A. Lerner, M.D. Of Counsel, Allen Matkins President, The Scripps Research Institute Judicial Appointments Advisor for Governor Arnold Schwarzenegger Claudia S. Luttrell Thomas E. Dewey, Jr. President, The Skaggs Institute for Research Member, McFarland Dewey & Co., L.L.C. James R. Mellor Former Chairman and Chief Executive Officer General Dynamics Corporation The Hon. Lynn Schenk Former Congresswoman, California Ralph J. Shapiro Chair, Avondale Investment Company Mark S. Skaggs Board Member, The ALSAM Foundation The Hon. Alice D. Sullivan (Ret.) California Superior Court Judge, Retired Chris D. Van Gorder President and Chief Executive Officer, ScrippsHealth Andrew Viterbi, Ph.D. President, Viterbi Group, L.L.C. OFFICERS Richard A. Lerner, M.D. President Human keratinocyte polarising in response to Douglas A. Bingham EGF-1. Microtubules are shown in red, Clip170 a microtu- Executive Vice President and Chief Operating Officer and Secretary bule + end binding protein in yellow, and EB1 different micro- Donna J. Weston tubule + end binding protein in blue. Work done by Ann Wheeler, Senior Vice President and Chief Financial Officer and Treasurer Ph.D., Research Associate, in the laboratory of Clare Waterman- Storer, Ph.D., Department of Cell Biology. Thomas E. Northrup, Esq., Ph.D. Chief Business Counsel and Assistant Secretary THE SCRIPPS RESEARCH INSTITUTE 2006 3 BOARD OF SCIENTIFIC GOVERNORS Dr. Gunter Blobel* Dr. Inder Verma The Rockefeller University The Salk Institute New York, New York La Jolla, California Professor Piet Borst Dr. Semir Zeki The Netherlands Cancer Institute University College Amsterdam, the Netherlands London, England Dr. Sydney Brenner* The Salk Institute * Nobel Laureate La Jolla, California Dr. Michael S. Brown* The University of Texas Southwestern Medical Center Dallas, Texas Professor Jean-Pierre Changeux Institut Pasteur Paris, France Dr. Samuel Danishefsky Memorial Sloan-Kettering Cancer Center and Columbia University New York, New York Professor Raymond A. Dwek, F.R.S. University of Oxford Oxford, United Kingdom Professor Mitchell Feigenbaum The Rockefeller University New York, New York Dr. Edmond Fischer* University of Washington Seattle, Washington Dr.Walter Gilbert* Harvard University Cambridge, Massachusetts Dr. Joseph L. Goldstein* The University of Texas Southwestern Medical Center Dallas, Texas Dr. Paul Greengard* The Rockefeller University New York, New York The synapse revealed. The artist created a pencil sketch Dr. Har Gobind Khorana* based on micrograph data, but opted to cut the number of neu- Massachusetts Institute of Technology ronal interactions to ~ 30% in order to clarify the physiology. He Cambridge, Massachusetts constructed 3-dimensional models of two cells to render on top Professor Aaron Klug* of the approved sketch. He designed a texture map to skin the Medical Research Council Laboratory of Molecular Biology two primary neurons that would insinuate a proteinated bilayer Cambridge, England and simultaneously simulate organelles deep to the surface. Light- ing sweeps attention over the entire image before settling it on Professor Sir Harold Kroto, F.R.S.* the synapse by reflecting hints of color from the focus into periph- University of Sussex Falmer, Brighton, United Kingdom eral regions of the drawing. Cool desaturated colors in the back- ground allow the warm synapse region to command attention as Dr. Phillip A. Sharp* it glows with a hint of anticipatory presynaptic transmission. This Massachusetts Institute of Technology image received a Certificate of Merit award from the Association Cambridge, Massachusetts of Medical Illustrators and won first place in the National Science Dr. Susumu Tonegawa* Foundation’s Scientific Visualization Challenge of 2005 compe- Massachusetts Institute of Technology tition. Illustration by Graham Johnson, courtesy of the Howard Cambridge, Massachusetts Hughes Medical Institute ©2004. 4 THE SCRIPPS RESEARCH INSTITUTE 2006 ADMINISTRATION Richard A. Lerner, M.D. Judith T. Muñoz, Ph.D. President Vice President, Human Resources Douglas A. Bingham Polly A. Murphy, DVM, Ph.D. Executive Vice President and Chief Operating Officer Senior Vice President, Business and Scientific Services Donna J. Weston Harry Orf, Ph.D. Senior Vice President and Chief Financial Officer Vice President, Scientific Operations, Scripps Florida Emily M. Holmes, Ph.D. William R. Roush, Ph.D. Vice President, Research Services Associate Dean, Graduate Studies, Scripps Florida Gerald F. Joyce, M.D., Ph.D. Denise M. Scalzo Dean, Faculty Vice President,
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