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The Skaggs Institute
for Chemical Biology
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.
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