News and Publications

2002 DEPARTMENT HIGHLIGHTS

Kurt Wüthrich, Ph.D., Cecil H. and Ida M. Green Visiting Professor of Structural Biology and member of The Skaggs Institute for Chemical Biology, was awarded the 2002 Nobel Prize in Chemistry for applying the technique of nuclear magnetic resonance to solving the structure of biological macromolecules. (See interview, page 5.)

Professor Charles Brooks, Ph.D., and Professor David Case, Ph.D., are part of a group of scientists from local research institutions who have been awarded $10.5 million over the next five years from the National Science Foundation to establish a leading center in the emerging field of theoretical biological physics, the Center for Theoretical Biological Physics. Biological physics encompasses such areas as spectroscopy and structural biology, which use the discoveries and the laws of physics to study problems in biology.

Professor Ian Wilson, D.Phil., was elected to membership of the American Academy of Arts and Sciences, an honor that is the result of a highly competitive process recognizing those who have made preeminent contributions toa scholarly field or profession.

Assistant Professor Flavio Grynszpan, Ph.D., and Associate Professor Vito Quaranta, M.D., received seed funding from the California Breast Cancer Research Program to design breast cancer drugs. The scientists plan to use the $136,000 to develop inhibitors of proteins that belong to a family of enzymes, matrix metalloproteinases, known to be responsible for the invasive properties of breast cancer cells.

2002 RESEARCH HIGHLIGHTS

Professor Paul Russell, Ph.D., and Professor John Yates, Ph.D., (Department of Cell Biology) characterized an enzyme, Cid13, as playing a novel role in regulating the expression of a gene in fission yeast Schizosacharomyces pombe. The collaborators determined that the enzyme was involved in RNA metabolism. This finding may have implications for the treatment of cancer.

A team of researchers led by Peter Wright, Ph.D., professor, chair, and Cecil H. and Ida M. Green Investigator in Medical Research, and Jane Dyson, Ph.D., professor, solved the structure of a protein essential for cancer tumor growth. Blocking this protein, HIF-1, has already proven effective in stopping tumor growth.

Using a combination of chemistry and molecular genetics, Assistant Professor Tianwei Lin, Ph.D., Professor John Johnson, Ph.D., and colleagues found a way to attach a wide range of molecules to the surface of a virus, enhancing the virus with the properties of those molecules. Their technique may find applications in materials science, medicine, and molecular electronics. One possible application is to build circuits of conducting molecules on the surfaces of viruses and form a component of a molecular-scale computer.

A group of scientists led by Wright and Dyson solved the structure of a nuclear receptor activator and the general transcription coactivator, CBP, two critical human proteins that are normally unstructured in the cell, but fold synergistically so that together they form an active biological structure. The structures may lead to new therapies, since the proteins are important regulators of genes essential for development and reproduction and are implicated in cancer and other diseases.

Paul Schimmel, Ph.D., Ernest and Jean Hahn Professor and Chair of Molecular Biology and Chemistry, and Associate Professor Martin Friedlander, M.D., Ph.D., (Cell Biology) found that a naturally occurring protein, tryptophanyl-tRNA synthetase, is a potentially potent inhibitor of angiogenesis, the process whereby new blood vessels are formed from existing ones. Since abnormal angiogenesis is the leading cause of eye diseases such as age-related macular degeneration and diabetic retinopathy--affecting tens of millions in the United States--this finding may lead to important new therapies.

A team of chemists led by Carlos Barbas III, Ph.D., professor and Janet and W. Keith Kellogg II Chair in Molecular Biology, used novel aldehyde chemistry and the amino acid proline as a catalyst to selectively synthesize a number of compounds, including novel functionalized amino acids and derivatives. These compounds have the potential to be converted into antibiotics or unusual amino acids, which are common to HIV protease inhibitors.

A collaboration between Wilson and Chi-Huey Wong, Ph.D., (Chemistry) who is Ernest W. Hahn Professor and Chair in Chemistry, and their colleagues in the Departments of Chemistry, Molecular Biology, and The Skaggs Institute for Chemical Biology yielded one of the best views ever of an enzyme (D-2-deoxyribose-5-phosphate aldolase) caught in the act of catalyzing a reaction on its substrate. This research should prove invaluable as a tool for drug synthesis.

Simultaneous reports by two TSRI teams, led by Russell, and Associate Professor Clare H. McGowan, Ph.D., identified the "resolvase" enzyme that may be responsible for generating genetic diversity during sexual reproduction. The discovery of the enzyme could lead to improved cancer chemotherapy.