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The Skaggs Institute
for Chemical Biology


Scientific Report 2006




President's Introduction


I am proud to report on the progress of the Skaggs Institute for Chemical Biology and the accomplishments of its members that are so vital to The Scripps Research Institute as a whole. In 2006, researchers at the Skaggs Institute once again left their mark on science, forging new paths toward our shared goal of improving human health.

Research Highlights

Investigators at the Skaggs Institute focus on the vital intersection between chemistry and biology. Their key 2006 studies include these remarkable highlights:

  • In what may be the first published breakthrough of its kind in the global battle against obesity, Professor Kim Janda; Assistant Professor Eric Zorrilla, Molecular and Integrative Neurosciences Department; and colleagues developed an vaccine against obesity that significantly slowed weight gain and reduced body fat in animal models.
  • Professor Ian Wilson led an effort to identify a possible pathway for a particularly virulent strain of the “bird flu” virus (H5N1) “to gain a foothold in the human population.” In another line of research, Dr. Wilson collaborated with Professor James Paulson, Department of Molecular Biology, to develop a new technology called a glycan microarray to survey samples of coat proteins from various strains of human and avian influenza viruses, including the virus from the deadly 1918 outbreak known as the Spanish Flu.
  • In the culmination of 5 years of work, Professor Tamas Bartfai; Associate Professor Bruno Conti, Molecular and Integrative Neurosciences Department; and colleagues published an article on their findings that reducing the core body temperature of mice extends the animals’ median life span by up to 20%. This research is the first to show that changes in body temperature can affect life span in warm-blooded animals.
  • Several scientists at the Institute showed the potential of an innovative combination of immunotherapy and small-molecule drug design for producing antibodies that target cancer cells. One study, led by Professor Carlos Barbas, highlighted the potential of such an approach against melanoma. In another study, Associate Professor Subhash Sinha and I developed a compound against metastatic breast cancer.
  • Professor Chi-Huey Wong and colleagues discovered a class of compounds that block replication of the virus that causes severe acute respiratory syndrome, a finding that may open the door to new drug targets against the deadly disease.
  • Professor Dale Boger; Brendan Crowley, a Ph.D. candidate at the Kellogg School of Science and Technology; and colleagues reengineered the well-known antibiotic vancomycin to ensure its effectiveness against both vancomycin-sensitive and vancomycin-resistant enterococci, a common strain of bacteria responsible for widespread hospital infections.
  • Professor John Tainer and colleagues determined the crystal structure and molecular mechanisms of a key part of WRN, a protein that protects humans from premature aging and cancer. They also uncovered the structural chemistry behind the bacterial type IV pilus filament, which plays an essential role in allowing antibiotic-resistant strains of Neisseria gonorrhoeae to escape the immune system and cause persistent and recurrent gonococcal infections.
  • ; Using an innovative profiling strategy, Professor Benjamin Cravatt characterized an enzyme that is “highly elevated” in aggressive human tumor cells. When the enzyme, KIAA1363, was inactivated, it impaired tumor growth and migration in both ovarian and breast cancer cells, suggesting that inhibitors of this enzyme may be valuable in the treatment of multiple types of cancer.
  • Professor Peter Wright and colleagues detailed a new hypothesis of how a key catalytic enzyme, dihydrofolate reductase—the target of several anticancer and antibiotic therapies—cycles through structural changes as it plays a critical role in promoting cell growth and proliferation.

Faculty News

As in previous years, in 2006 faculty members of the Skaggs Institute were recognized as leaders in their field.

Professor Dale Boger was elected to the American Academy of Arts and Sciences. Fellows of the academy are selected through a highly competitive process that acknowledges individuals who have made preeminent contributions to their disciplines and to society at large.

Professor and Department of Chemistry chair K.C. Nicolaou won both the 2006 G.M. Kosolapoff Award from the Auburn section of the American Chemical Society and Germany’s Burkhardt-Helferich Prize. He is also an author of one of Chemical Abstracts Service’s 10 most-requested papers (second quarter), “Palladium-Catalyzed Cross-Coupling Reactions in Total Synthesis,” in Angewandte Chemie.

Two articles on “click chemistry” by Professor K. Barry Sharpless; Associate Professor Valery Fokin, Department of Chemistry; and Associate Professor M.G. Finn were among the Chemical Abstracts Service’s 10 most-requested patent families (second quarter).

Professor Ian Wilson oversaw the opening of a new robotic crystallization facility on the Scripps Research La Jolla campus in May. One of the largest machines of its kind, the integrated robotics system will enhance scientists’ ability to solve molecular structures, increasing our understanding of basic biology and strategies for combating a variety of diseases.

Two faculty members of the Skaggs Institute took on revised roles within the Scripps Research administration as part of an initiative to enhance efficiency and communication. Professor Gerald Joyce is now dean of the faculty, and Professor Jeffery W. Kelly is dean of graduate and postgraduate studies.

Extraordinary Generosity

I extend my congratulations to my Skaggs Institute colleagues on another outstanding year, made possible by the extraordinary generosity of the Skaggs family and the ALSAM/Skaggs Institute for Research.

This year’s achievements make me proud to be part of The Scripps Research Institute. My congratulations go out to faculty, staff, postdoctoral fellows, students, trustees, and loyal supporters for another year well done.

 



Richard A. Lerner, M.D.
President, Scripps Research

Lita Annenberg Hazen Professor of Immunochemistry

Cecil H. and Ida M. Green Chair in Chemistry