Report from the Fifth Annual Maria Goeppert-Mayer Symposium

UNIVERSITY OF CALIFORNIA, SAN DIEGO — Surface structure, the glass transition, oxidative damage to DNA, microelectronic arrays, and cell surface engineering were the topics at the Fifth Annual Maria Goeppert-Mayer Symposium, held at SDSC on March 4.

"All of the symposium talks this year, as in previous years, were united by their attention to interactions and interfaces, and all the talks illustrated the interdisciplinarity that has become the hallmark of this event," said symposium co-organizers Kim Baldridge, senior principal scientist at SDSC and adjunct associate professor of chemistry in the UCSD Department of Chemistry and Biochemistry, and Tammy Dwyer, associate professor of chemistry at the University of San Diego.

In addition to five invited speakers, the symposium featured nearly 30 posters presented by members of research groups at Arizona State University, Caltech, UCSD, UCLA, the Salk Institute for Biological Studies, and the Weizmann Institute (Israel). More than 120 people attended the lectures and poster session.

The symposium, originated by Baldridge, is organized each year at UCSD to honor the work of Maria Goeppert-Mayer (1906-1972), who was awarded the Nobel Prize in physics in 1963 while a professor at UCSD. Her life was briefly reviewed at the 2000 symposium by Marjorie Caserio, professor emeritus of chemistry at UCSD, who pointed out that Mayer's first official professorial position came with her appointment to UCSD at the age of 54. "Nevertheless," Caserio said, "Mayer had achieved excellence in science much earlier and had, throughout her life, a very strong support system, with encouragement from her parents and from the scientists with whom she studied at Goettingen, as well as a continuing surround of intellectual stimulation in a series of academic environments. This symposium is part of the new support system that is being built to encourage similar scientific achievement, and thus it is an entirely appropriate tribute to Mayer's role as a leading scholar and her unflagging pursuit of excellence in science."

This year's symposium was sponsored by the San Diego Supercomputer Center; the University of California, San Diego; the National Biomedical Computational Resource; the American Chemical Society; and Cray, Inc. (formerly Tera Computing).

Imaging Surface Structure
The first speaker was Shirley Chiang, professor of physics at UC Berkeley. She was introduced by Theresa Harper of Arizona State University. Chiang, who was elected a Fellow of the American Physical Society (APS) in 1995, served on the selection committee for the APS's own Maria Goeppert-Mayer Award (which went this year to another symposium speaker, Sharon Glotzer).

Chiang's topic was imaging surface reactivity through atomic microscopy. She showed the way in which microscopes of varying resolution and capabilities could be used to study the properties of solid surfaces and interactions taking place on such surfaces. She illustrated her talk with examples from recent studies by her group of small organic molecules on such metals as platinum, palladium, and rhodium. Chiang and her group are developing a variable-temperature scanning tunneling microscope combined with an atomic force microscope, to enable the fabrication of small nanostructures, the investigation of phase transitions in adsorbed layers, and the study of the mechanical properties of atomic-scale materials at low temperatures. The group is also using a low-energy electron microscope in conjunction with a synchrotron at the Lawrence Berkeley Laboratory for high-resolution X-ray photoemission microscopy.

Mystery of Mysteries: The Glass Transition
The second speaker was Sharon C. Glotzer of the Polymers Division of the National Institute of Standards and Technology (NIST). She was introduced by Stacy Canan-Koch of Agouron Pharmaceuticals, who noted that Glotzer had done her undergraduate work at UCLA and received her Ph.D. in theoretical and condensed matter and statistical physics from Boston University in 1993, working under the direction of H. Eugene Stanley. Since January 1999, Glotzer has been the director of the Center for Theoretical and Computational Materials Science at NIST's Materials Science and Engineering Laboratory. She received the American Physical Society's Maria Goeppert-Mayer Award in 2000. The award cited "her ingenious use of computational physics to probe a wide range of novel materials under different conditions [and] demonstrating the existence and nature of spatially correlated dynamic heterogeneities in glass-forming liquids."

Her topic was just such heterogeneities, as observed using better algorithms and better interaction potentials in molecular dynamics simulations. She quoted Princeton physicist Philip Anderson's observation that the nature of the transition from a liquid to a glassy state "remains the deepest and most important unsolved problem in solid-state physics." What makes a liquid turn into either an ordered crystal or a disordered glassy structure?

As Glotzer's simulations show, one key is that molecules are moving trillions of times faster in a liquid. As the temperature is lowered, the bulk slows down and the viscosity change makes them behave "like a crowd in a subway train." That is, they move with a certain amount of "cooperativity," because they can do nothing else. Yet within this cooperating crowd, Glotzer observes a faster population of highly mobile molecules that cluster and accrete in distinct ways, their spatially heterogeneous dynamics governing the early stages of the glass transition. Glotzer showed a video of the spatial correlations of particles escaping from the "crowd" in a Lennard-Jones binary mixture and in a polymer melt. The statistics of the motions of these particles have been tested in a number of colloidal suspensions, and the figures of merit emerging from all the calculations now done by Glotzer and colleagues are proving reliable guides to transitional behavior.

Chemistry and Biochemistry of Guanine Oxidation: A Detective Story
Cynthia J. Burrows, professor of chemistry at the University of Utah, was introduced by Barbara Sawrey of the UCSD Chemistry and Biochemistry Department, who noted that Burrows received her doctorate from Cornell in 1982, did postdoctoral work in Strasbourg, and was a professor at the State University of New York, Stony Brook, before joining the Utah faculty in 1995.

Burrows explained that her group's research lies at the interface of organic, inorganic, and biological chemistry, involving questions in catalysis, mechanism, coordination chemistry, nucleic acid structure, and medicinal chemistry. In particular, they are interested in mechanisms of oxidative damage of biopolymers, since such damage is implicated in the inauguration of processes associated with aging, toxicity, or tumorigenesis. One of their major interests is the activity of guanine, the most easily oxidized nucleobase. In the presence of transition metal complexes (molecules containing nickel, cobalt, or copper), guanine is oxidized to 8-Oxo-7,8-dihydroguanosine, known as 8-Oxo-G, which is a marker of oxidative damage in cells.

Burrows and her group have been exploring the further oxidation of 8-Oxo-G via one-electron oxidants. In previous studies, they had observed two products of 8-Oxo-G oxidation in the presence of an iridium salt, and one was thought to be an intermediate to the other. But when prolonged heating failed to convert the two products into the final product, the group decided to investigate further. What they found was that subtle differences between the environment of 8-Oxo-G as monomer versus polymer led to entirely different chemistries. Their research was published just after the symposium in the journal Organic Letters. The identification of a new pathway to a previously unknown oxidation product of 8-Oxo-G opens the door to studies of the way in which this product is repaired (or not) when it occurs along sections of DNA already compounded with 8-Oxo-G.

Microelectronic DNA Arrays for Genomic Research
Tina Nova of Biostruct was introduced by Karla Ewalt of Nanogen. Nova received her Ph.D. in biochemistry from UC Riverside and began her corporate career at Hybritech in San Diego, where she led the development of several widely used products, including the PSA test for the detection of prostate cancer. She was a founder and executive director of Ligand Pharmaceuticals, and then founded Selective Genetics. In 1994 she joined Nanogen as its fourth employee and served until January 2000 as President, Chief Operating Officer, and a member of the Board of Directors. Biostruct, Nova's new venture, will provide comprehensive facility outsource services to the biotech and pharmaceutical industries.

Nova spoke about active microelectronic DNA arrays for genomic research, pharmacogenetic, and drug discovery applications, reviewing the technological advances made at Nanogen during her tenure there. She discussed the standard 100-test-site microelectronic array, which contains all test sites within a 2 mm square on the chip. Only a few microliters of product is needed to cover the test area. She also discussed a custom 10,000-site chip and showed videos of the way in which the chips enable the identification of single-nucleotide polymorphisms (SNPs) in genes that code for a given protein. She reviewed a number of collaborations between Nanogen and biomolecular research groups that were formed to test the technology and to achieve scientific advances. For example, one study focused on human mannose binding protein (MBP), which is a key component of the innate immune system in children who have not yet developed immunity to a variety of pathogens. There are four alleles of the gene that codes for MBP, each differing by only a single nucleotide. In a study of genes from multiple patients, the Nanogen chip technology was able to discriminate among alleles in a series of successively more complex assays. Other applications include forensic identification of short tandem repeat loci and the identification of variations in genes coding for thiopurine methyltransferase (problems with this metabolic pathway lead to leukemia, Crohn's disease, and other serious disorders),

Merging Chemistry and Biology on the Surfaces of Cells
Carolyn Bertozzi of the Department of Chemistry and Molecular and Cell Biology at UC Berkeley was introduced by Dwyer, who noted that Bertozzi had received her undergraduate degree in chemistry from Harvard, worked at Bell Labs, then joined the graduate program at UC Berkeley, receiving her Ph.D. in 1993. She was a postdoctoral researcher in immunology with Steven Rosen at UC San Francisco, then returned to Berkeley to join the chemistry faculty in 1996. She is now an associate professor and a recent MacArthur Award winner. Bertozzi discussed her current research, which focuses on enzymes that regulate the biological activity of cell surface proteins and new methods for engineering the biochemical recognition activity of cell surfaces.

Cell surface molecules are important because they participate in fundamental processes such as cell adhesion and signal transduction. The predominant carriers of molecular information found on cell surfaces are glycoconjugates (glycoproteins and glycolipids), decorated with oligosaccharides. Three years ago, Bertozzi and her group developed ways of attaching ketone groups to the oligosaccharides, remodeling cell surfaces to produce novel receptor binding activities and other new surface chemistry.

In work done just recently with graduate student Eliana Saxon and published in the March 17 issue of Science, Bertozzi has developed a new means for performing reactions on the surfaces of cells by binding small molecules called azides to cell surface glycoconjugates, using a modification of a Staudinger reaction. The original reaction, developed in 1919 by Hermann Staudinger (the 1953 Nobel laureate in chemistry), is an abiotic reaction between a phosphine and an azide that produces an aza-ylide. Bertozzi and Saxon modified the reaction to stabilize the aza-ylide, which normally hydrolyzes spontaneously in water. What is particularly interesting is that by this means they are not only able to install azides on cell surfaces, but also in the interiors of cells, permitting very specific chemical exploration of the intracellular environment. The work was also hailed in the Science/Technology column of the March 27 issue of Chemical and Engineering News.

Poster Session Awards
The awards for best poster went to three graduate researchers: Leah-Nani Alconcel from the UCSD group of chemist Robert Continetti, Bruce Heitbrink from the group of chemist Ken Houk at UCLA, and Kharissia Pettus, from the UCSD group of chemist Andrew C. Kummel.
"This was the most successful symposium to date," Baldridge said, "and the continued acquisition of sponsorship means that we can aim for another fantastic one next year. We're very grateful to the ACS, NBCR, SDSC, UCSD, and Tera for help in the organization." —MM
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