The Skaggs Institute
for Chemical Biology
I am proud to
report on some of the many accomplishments at The Skaggs Institute for Chemical
Biology at The Scripps Research Institute during the past year.
This past year's scientific findings
from scientists at the Skaggs Institute are, as in earlier years, extraordinary.
- Professor Chi-Huey Wong and colleagues
developed a new 2-punch strategy against HIV and successfully tested aspects of
the strategy in the laboratory. The investigators created devices they call glycodendrons
that are designed to do 2 things at once: (1) inhibit the transport of HIV from
where it traditionally enters the body, preventing the virus from moving deeper
inside where it can infect immune cells, and (2) set up an immune antibody response
to a unique carbohydrate structure on the surface of the virus.
- Professor Kim Janda, Associate
Professor Eric Zorrilla (Scripps Research), and colleagues discovered a catalytic
antibody that degrades a known appetite stimulant. The antibody works against the
gastric hormone ghrelin, which has been linked to weight gain and fat storage. These
findings may lead to a potentially novel treatment for obesity.
- Using samples from survivors of
the 2005–2006 "bird flu" outbreak in Turkey, an international team,
including researchers at Sea Lane Biotechnologies, L.L.C., Atherton, California,
and me, created the first comprehensive libraries of monoclonal antibodies against
avian influenza virus (type H5N1). These antibody libraries may be useful in developing
a therapy that could stop an influenza pandemic and provide treatment to the people
infected and in pointing the way to the development of a universal flu vaccine.
- Paul Schimmel, Ernest and Jean
Hahn Professor and Chair in Molecular Biology and Chemistry, and colleagues uncovered
2 surprising new methods for correcting mistakes in protein production. This editing
system is important because even small mistakes in protein production can have profound
- Jeffery Kelly, chair of the Department
of Molecular and Experimental Medicine and Lita Annenberg Hazen Professor of Chemistry,
and colleagues discovered that 2 widely available prescription drugs restore partial
cellular folding, trafficking, and function to a variety of mutant enzymes responsible
for 3 distinct lysosomal storage diseases, maladies involving failure of multiple
organ systems. The team found that the calcium channel blockers diltiazem and verapamil,
which are used to treat hypertension, increased the overall function of mutant lysosomal
enzymes associated with Gaucher disease, α-mannosidosis,
and type IIIA mucopolysaccharidosis in cell lines derived from tissues from patients
with these diseases.
- Professor John Tainer and colleagues
revealed how tiny mutations in a single gene can produce 3 strikingly different
childhood diseases. The scientists solved a crystal structure of the enzyme XPD
helicase, which unwinds DNA to fix damage that regularly occurs. This research sheds
light on 3 different inherited syndromes: xeroderma pigmentosum, which increases
the risk for skin cancer by several thousandfold, and Cockayne syndrome and trichothiodystrophy,
which are premature aging and developmental disorders.
- Professor Elizabeth Getzoff and
colleagues developed a new method for chemically targeting a single enzyme to block
production of nitric oxide without limiting the beneficial production of this oxide
by other closely related enzymes. The technique provides a general solution that
should enable development of new drugs to treat medical problems linked to nitric
oxide overproduction, such as arthritis, and may aid in the discovery of treatments
for other conditions such as HIV disease and AIDS.
- Professor Gerald Joyce, dean of
the faculty, and colleagues demonstrated genetic adaptation to selective pressure
in real time. Under the control of a computer, a population of billions of genes
went through 500 cycles of forced adaptation to emerge as molecules that could grow
faster and faster on a continually dwindling source of chemical fuel.
- Professor Peter Schultz, who holds
the Scripps Family Chair, and colleagues produced a powerful immune response in
mice by incorporating an unnatural amino acid into a target protein. This novel >approach could be useful in developing new
vaccines for cancer, infectious diseases, and other disorders.
- Professor Benjamin Cravatt, chair
of the Department of Chemical Physiology and director of the Helen L. Dorris Child
and Adolescent Neuro-Psychiatric Disorder Institute, and colleagues did a protein
survey that nearly tripled the number of proteins known to be involved in programmed
cell death and refuted a long-held idea about the life cycle of proteins. The findings
may open doors for the discovery of new drugs.
It is with great sadness that I report
the death, on October 5, 2008, of Professor Ernie Beutler, chair of the Department
of Molecular and Experimental Medicine since 1978. His passing is a great loss to
science, to the Skaggs Institute and Scripps Research, and to all who knew and worked
with him over his long, brilliant career. It is difficult to adequately acknowledge
his host of significant discoveries—among them X-inactivation and novel treatments
for Gaucher disease and several forms of leukemia, including hairy cell leukemia—or
to fully recognize his authorship of more than 1000 scientific articles in all the
leading journals in his field, his numerous monographs and book chapters, and his
editing of the widely used textbook Williams Hematology. He was an extraordinary
man who led an exceptional life, and I am most thankful that he crossed our path
and stayed with us for so long.
Filling the position of chair of the
Department of Molecular and Experimental Medicine is Jeffery Kelly, who also recently
became chair of the Board of Trustees of the Skaggs Institute for Research.
Assuming the deanship of the Kellogg
School from Dr. Kelly is Professor Jamie Williamson. Dr. Williamson will build on
his 7 years as associate dean to lead this top-ranked graduate program into the
In 2008, members of the Skaggs Institute
again received many honors and awards.
- Professor Peter Wright, chair
of the Department of Molecular Biology and Cecil H. and Ida M. Green Investigator
in Biomedical Research, was acknowledged for his outstanding research achievements
by election to the National Academy of Sciences.
- Professor Albert Eschenmoser won
the Benjamin Franklin Medal in Chemistry. Franklin Institute Awards are given for
outstanding achievements that have enhanced the quality of human life and deepened
our understanding of the universe. Dr. Eschenmoser was recognized for his research
on the structure of nucleic acids, leading to the understanding of why RNA and DNA
have the structures they do.
- Professor Ian Wilson was showered
with honors, including an honorary degree from the University of St. Andrews in
Scotland in recognition of achievements "at the forefront of research to understand
the immune system and influenza"; election as a Corresponding Fellow to the
Royal Society of Edinburgh, Scotland's National Academy of Science and Letters;
and election to the Board of Directors of the Keystone Symposia.
- Professor Carlos Barbas III received
the 2009 Tetrahedron Young Investigator Award, Bioorganic and Medicinal Chemistry,
an award for scientists less than 45 years old who have exhibited "exceptional
creativity and dedication" in their fields. In addition, Dr. Barbas was chosen
for the American Chemical Society Arthur C. Cope Scholar Award, which recognizes
excellence in organic chemistry.
- Jeffery Kelly won the American
Peptide Society's Vincent du Vigneaud Award, sponsored by Bachem, Inc., Torrance,
California, for "fundamental, visionary research on folding and aggregation
processes in peptides and proteins, and for courageous, insightful exploration of
the biological and medical implications of his discoveries."
I am delighted to take this moment to
appreciate the many, significant accomplishments that have brought us this far,
through the extraordinary generosity and continuing support of the Skaggs family.
Thank you also to the many members of the Scripps Research community, including
donors, trustees, friends, faculty, staff, postdoctoral fellows, and students, for
your dedication, hard work, and vision.