The Skaggs Institute
for Chemical Biology
1996, The Skaggs Institute for Chemical Biology was established at Scripps Research
through a gift from Sam and Aline Skaggs. Since then, more than $100 million has
been contributed to the research efforts at the institute. This funding supports
30 principal investigators and, in 2007 alone, fellowships for 250 postdoctoral
fellows and graduate students. The individual reports of the principal investigators
of the institute are provided elsewhere in this report; only a few of the highlights
of research from the past year are given here.
a new member of the Skaggs Institute, studies sensory neurons that detect chemical
ligands (pheromones) that govern social behaviors. Her studies provide the tools
to investigate the molecular mechanisms that underlie human social behavior. Paul
Wentworth, Department of Chemistry, has elucidated the universal property of antibody
molecules to oxidize water to produce hydrogen peroxide. These studies point to
an earlier role of antibodies in immunity as a direct means to kill foreign pathogens
through oxidation. Jeff Kelly, dean of the graduate school, is using small synthetic
molecules to bind to and stabilize enzymes that prevent Gaucher disease. These molecules
act as chaperones and provide excellent leads for the development of therapeutic
agents for treatment of the disease.
has traced the origins of Charcot-Marie-Tooth disease to mutations in genes for
2 aminoacyl tRNA synthetases. These results indicate expanded functions for tRNA
synthetases in human cells that now include neurogenesis. Dale Boger and his group
have synthesized molecules that inhibit fatty acid amide hydrolase. These inhibitors
increase the levels of endogenous analgesics that relieve neuropathic and chronic
pain. Dr. Boger and his group have also defined the structural details of vancomycin
action and how resistant bacteria elude this antibiotic. Through total synthesis,
they have prepared a vancomycin derivative that overcomes this resistance.
the new director of the Worm Institute for Research and Medicine, has observed a
startling aspect of Δ9-tetrahydrocannabinol,
the active component of marijuana. This molecule inhibits the amyloid aggregation
that leads to neurodegeneration in Alzheimer's disease and provides a new lead
for development of more conventional therapeutics for treatment of the disease.
Ulrich Müller, another new member of the Skaggs Institute, identifies and studies
genes that control the function of hearing in mammals. His results have led to animal
models for deafness and the pathogenic variance of the proteins that cause it.
continues to pursue the application of click chemistry, a reaction that has lowered
the obstacles that separate chemistry from biology and is widely used by chemical
biologists. He has also discovered that organic reactions that occur on water's
surface offer many advantages in synthesis. M. Reza Ghadiri uses rationally designed
small-molecule peptide scaffolds that present chemical functional groups in predictable
3-dimensional directions. These cyclic pseudopeptides provide a new platform for
drug design. Elizabeth Getzoff has studied the 3-dimensional structures of the enzymes
superoxide dismutase and nitric oxide synthase. These catalysts are involved in
neuronal cell death and are key therapeutic targets for the pharmaceutical industry.
My own research
in collaboration with Tamas Bartfai, Molecular and Integrative Neurosciences Department,
has led to small-molecule modulators of the immune system. These modulators have
excellent activity in animal models of pain and fever. In other studies, members
of my laboratory are synthesizing mimics of protein surfaces to provide tools for
determining how molecules fit together in biological systems.
overview covers just a few of the advances made in the past year, all of us in the
Skaggs Institute are dedicated to reducing human suffering by finding cures for
diseases. We are grateful to the Skaggs Institute for Research for encouraging our
studies at the frontiers of science and to the Skaggs family for their continued