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News and Publications
Year In Review - 2000
Julius Rebek, Jr., Ph.D., Director
he Skaggs Institute for Chemical Biology is now in its fifth year, thanks to the extraordinary generosity of Aline and Sam Skaggs. Research is conducted at the interface of chemistry and biology with the long-term goal of finding cures for a broad range of diseases. Primary efforts are focused on organic synthesis, antibody catalysis, protein structure, RNA chemistry and molecular recognition.
The Skaggs Institute supports 29 principal investigators and more than 200 researchers. These scientists are also members of other departments including chemistry, cell biology, molecular biology, neurobiology and molecular and experimental medicine. The collaborations and synergy that link the research programs is one of the Institute's greatest strengths. As a result, its members have established a working environment that is genuinely diverse -- multi-disciplined, multi-talented and recognized for its growing number of accomplishments worldwide.
Peter Schultz, Ph.D., Professor, Department of Chemistry, was appointed to The Skaggs Institute last year. A co-discoverer of catalytic antibodies, his breadth of interest and unbounded energy will continue to expand the genetic code, and apply a combinatorial approach to research in biological chemistry. The other co-discoverer of catalytic antibodies, TSRI President Richard Lerner, together with Subhash Sinha, have used these molecules to synthesize epothilones, promising chemotherapeutic agents.
A MODEL FOR INTERACTIVE RESEARCH
While the Institute's ability to sustain broad, long-term projects makes it unique, a more subtle accomplishment is its collaborative efforts between research groups. As a result, The Skaggs Institute has become a model for interactive chemical biology research. Some of the projects are practical, while others are focused on developing the next generation of molecules targeted against disease.
A number of innovative research activities define the growing spirit of the Institute and create a unique environment for the practice of chemical biology. The research on antibodies, for example, focuses on antibody catalysis -- from developing new molecular sensors to detecting nerve gas agents to the production of antibodies in microalgae, which may eventually lead to the future development of human therapeutic and other important proteins.
In chemistry, Chi-Huey Wong, Ph.D., was selected to receive a 2000 Presidential Green Chemistry Award presented by the U.S. Environmental Protection Agency, the director of the White House Office of Science and Technology and the president of the American Chemical Society. Wong's research centers on the use of enzymes for chemical synthesis, particularly molecules that bind to RNA, a rapidly emerging target for development of new antibiotics.
Another area of primary focus is cancer research. Last year, the anticancer agents epothilones and eleutherobins were synthesized, first as individual molecules and then as combinatorial libraries that allow scientists to quickly modify the chemical structure of these powerful agents. Combinatorial chemistry has captivated the Sharpless group; Professor Sharpless received the National Academy of Sciences Award in Chemical Sciences this year for these and other significant research accomplishments.
The organic chemistry of proteins is the area of research in Dr. Jeff Kelly's group, while Dr. Reza Ghadiri's lab confronts the frontier of chemical biology with its attempts to convert inanimate chemical reactions into animate chemistry. Ernest Beutler, M.D., Chairman of the Department of Molecular and Experimental Medicine, and his group study the regulation of apoptosis -- programmed cell death -- by various protein families.
Gerald Edelman, M.D., Ph.D., Director of the Neurosciences Institute and Chairman of the Department of Neurobiology, continues to study signaling mechanisms between molecules involved in cell adhesion, a process central to neural development.
In molecular biology, the focus continues to be the basis for genetic makeup. Topics of scientific investigation include uncovering the nature of the nucleic acid structure and why it is composed of particular sugars and bases, as well as the fundamentals of RNA -- the chemical messenger that spreads the DNA code to the body's cells. In the area of RNA chemistry, Paul Schimmel, Ph.D., pursues his study of the rules of the genetic code, primarily the enzymes that recognize both RNA and amino acids. The self-assembly of RNA and its ability to act as a catalyst have been explored by Dr. Martha Fedor's group. The dynamics of intermediates in RNA folding has yielded to the studies of James Williamson, Ph.D., and his coworkers. The cleavage of RNA by DNA enzymes is one of the recent accomplishments in Dr. Gerald Joyce's group. In Dr. John Tainer's lab, the study of protein structure in the solid state has yielded the crystal structure of molecules involved in DNA repair, while structural changes accompanying genetic mutations in diseases such as ALS (Lou Gehrig's disease) are the focus of Dr. Elizabeth Getzoff's group.
The scientists' work this year, as in the past, demonstrates the greatest benefit that comes from the highly collaborative and synergistic environment of The Skaggs Institute for Chemical Biology -- the ability to develop and sustain broad, long-term projects that go to the core of biological processes and human disease.
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