Issue Date: January 26, 2009
Nobel Laureate Signature Award For Graduate Education In Chemistry
Sponsored by Mallinckrodt Baker Inc.
Laura A. Banaszynski is described as both a thinker and a doer by her graduate school adviser, Stanford University chemical and systems biology professor Thomas J. Wandless, who nominated Banaszynski, 30, for this award on the basis of her dissertation research in two areas of biological chemistry.
Banaszynski's first project was to investigate the immunosuppressant drug and anticancer agent rapamycin and its ternary complex with FK506 binding protein (FKBP12) and the enzyme mTOR. It was not a straightforward effort, Wandless notes. After the lab's standard approaches to such problems didn't pan out, Banaszynski learned several new biophysical techniques that weren't routine in Wandless' lab.
Wandless, who will be honored as the awardee's preceptor, praises Banaszynski's ability not only to seek out knowledgeable people in other departments and at other schools to help her but also to learn enough about each technique to understand its strengths and weaknesses. In the end, she combined fluorescence polarization, surface plasmon resonance, and nuclear magnetic resonance spectroscopy on wild-type and mutated proteins to provide a complete molecular picture of the interactions between the proteins and rapamycin (J. Am. Chem. Soc. 2005, 127, 4715). The information could be useful for developing rapamycin analogs with more potent anticancer activity.
Banaszynski's second project involved designing a new approach to protein regulation by developing mutants of FKBP12 as so-called destabilizing domains that could be added to other proteins (Cell 2006, 126, 995). When a small cell-permeable ligand is available to stabilize the domain, the protein can function normally in the cell. When the ligand is absent, the unstable FKBP12 domain makes the protein vulnerable to proteases.
One of Banaszynski's goals with this project, Wandless says, was to use a ligand that could be easily synthesized and provided to others. After publication of the work, the researchers responded to more than 160 requests for the reagents. Stanford subsequently licensed the technology to Clontech Laboratories, which launched commercial kits in early 2008. Banaszynski went on to evaluate the application of the destabilizing domains to control protein function in living mice (Nat. Med. 2008, 14, 1123). She also investigated the use of the domains to regulate proteins to reprogram differentiated cells into stem cells.
"Banaszynski's work required complex chemical synthesis, molecular biology and genetic manipulation of cells and organisms, biochemical and biophysical analysis, microscopy, and whole-animal imaging," says Carolyn R. Bertozzi, a chemistry professor at the University of California, Berkeley, who provided lab space and equipment for Banaszynski to measure protein-ligand binding kinetics. "The bandwidth of experimental approaches that Banaszynski wielded and commanded is extraordinary."
Banaszynski received a B.S. in chemistry from the University of Notre Dame in 2000, after which she spent a year teaching impoverished children in Haiti. She received her Ph.D. from Stanford in 2007 and is now doing postdoctoral research in posttranslational modifications of histones in C. David Allis' lab at Rockefeller University.
Wandless, 42, centers his research program on developing new experimental techniques for regulating cellular proteins and processes. He received a B.S. from Trinity University, in Texas, in 1988 and a Ph.D. in chemistry in 1993 from Harvard University, where he also did postdoctoral work.
Wandless joined the chemistry department at Stanford in 1995 and moved to the medical school's department of chemical and systems biology in 2003. He has received several awards for both his research and teaching, including a Sloan Research Fellowship, the Camille Dreyfus Teacher-Scholar Award, the Beckman Young Investigator Award, the National Science Foundation Faculty Early Career Development award, and the Dreyfus New Faculty Award, along with two awards from Stanford for classroom teaching.
Banaszynski will present the award address before the Division of Biological Chemistry.
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