National Jewish Crystallographer Named Pew Scholar
Gongyi Zhang, PhD, an X-ray crystallographer whose bold approach to scientific problems has helped him solve structures of several important proteins, has been named a 2001 Pew Scholar in the Biomedical Sciences. He is one of 20 young investigators recognized each year by the Pew Charitable Trusts for their "outstanding promise in the basic and clinical sciences." Dr. Zhang, an assistant professor in the Integrated Department of Immunology at National Jewish and the University of Colorado Denver, will receive a $240,000 unrestricted award over a four-year period.
"He is not afraid to take on any problem," said National Jewish Senior faculty member and structural biologist John Kappler, PhD "He’s got his eye on the prize and he doesn’t stop until he gets it."
Dr. Zhang earned his PhD in X-ray crystallography in China. X-ray crystallographers determine the structure of proteins by analyzing the way the X rays bounce off protein crystals. Knowing the structure of a protein helps biologists understand how it functions and suggests targets for potential drugs or other interventions.
Dr. Zhang came to the United States as a post-doctoral fellow in the lab of National Institutes of Health crystallographer James Hurley, PhD There he determined structures of the catalytic core of adenylyl cyclase, and a regulatory domain of protein kinase C, important enzymes in signal transduction. Both Nature and Cell published his work.
Dr. Zhang took a second post-doctoral fellowship in the lab of Seth Darst, PhD, at Rockefeller University, where he began work on one of biology’s most important proteins, RNA polymerase. RNA polymerase transcribes genes, encoded in DNA, into RNA. RNA is translated into the proteins that serve as the body’s scaffolding and metabolic machinery.
RNA polymerase is a massive molecule whose structure had eluded scientists for decades. Dr. Darst’s lab was crystallizing and imaging small subunits of RNA polymerase, which they planned to combine into an image of the entire protein. Dr. Zhang decided it would take too long to analyze RNA polymerase one piece at a time and began work on the entire protein. Competing against much larger, more experienced laboratories, Dr. Zhang and his colleagues determined the structure of the core RNA polymerase in 1999. Their work was featured on the cover of Cell .
In addition to his bold approach, Dr.Zhang attributes his success in part to "protein engineering." Many proteins are difficult to crystallize because surface charges or flexible regions prevent them from aligning in regular, crystalline patterns. By combining a strong knowledge of both biology and crystallography, Dr. Zhang alters the genes that make the proteins. The altered genes produce a slightly different proteins, which are more amenable to crystallizing yet still retain their essential, functional structure.
Dr. Zhang came to National Jewish in 1999. He has continued his work on RNA polymerase and associated molecules that initiate the transcription of DNA into RNA. He has also begun numerous collaborations with immunologists at National Jewish. Among others, Dr. Zhang is working with Abrahm Kupfer, PhD, and John Kappler on protein kinase C theta, an enzyme involved in the activation of T cells; with Valerie Fadoc, PhD, on the phospatidylserine receptor, which recognizes the death wish of suicidal, or apoptotic cells; and with Hong-Bing Shu , PhD, on the TALL-1 protein, which plays an important role in the proliferation of B cells and autoimmune disease.
"My interests are broad," said Dr. Zhang. "We try to collaborate with almost every laboratory in the basic sciences here at National Jewish."
Links to abstracts of Dr. Zhang's papers
Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester.
Structure of the adenylyl cyclase catalytic core.
Crystal structure of Thermus aquaticus core RNA polymerase at 3.3 A resolution.
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