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Khoury Lecturer Tjian Unravels Secrets of Gene Expression

Two of the hottest topics in science today are HIV research and functional genomics. Ultimately, both require an understanding of how information encoded in genes gets translated into the proteins that become the building blocks of a virus or a cell, or helps them function.

Dr. Robert Tijian Dr. Robert Tjian, professor of molecular and cellular biology at the University of California, Berkeley, has played a major role in elucidating how genes are activated. On Wednesday, Sept. 29, he will present the George Khoury Lecture at 3 p.m. in Masur Auditorium, Bldg. 10. The title of his talk, "The Biochemistry of Eukaryotic Transcription: More Surprises and Complexities," hints at the unanticipated turns his research has made over the past two decades and projects a sophisticated process yet to be understood in the area of gene expression.

Tjian received his A.B. in biochemistry from the University of California, Berkeley, in 1971 and his Ph.D. in biochemistry and molecular biology from Harvard University in 1975. As a Harvard junior fellow at Cold Spring Harbor, he purified a protein, called the SV40 large T antigen, involved in regulating viral replication. This experience led to a lifetime focus on how cells control the expression of genes during development and cellular differentiation.

Many diseases arise when gene activity is not tightly controlled. Often gene activity is left to specific regulatory proteins that determine the rate at which the DNA "message" is copied or transcribed. For example, HIV uses the protein Tat to redirect cellular processes to obey instructions from HIV genes to make copies of the virus. If it can be specifically inhibited, replication of the virus might be halted without affecting production of normal cellular proteins.

Early in his career, Tjian realized that eukaryotic cells such as those in humans rely on complex DNA-protein interactions to control gene activity. His group successfully isolated the first human transcription factor, Sp1, and later discovered that helper proteins called coactivators work with transcription factors. Multi-subunit complexes are responsible for mediating gene activation. The different subunits help the complex recognize and control expression of the estimated 80,000 to 100,000 genes in the human genome.

Understanding the molecular machinery that determines gene activity can help explain how the same DNA in each cell can generate cells with separate functions, from an insulin-producing islet cell in the pancreas to a vision-enhancing rod cell in the eye. Ultimately, knowledge of how genes are expressed could provide a rational way to develop compounds that will fight breast cancer, Alzheimer's disease, diabetes, multiple sclerosis and even the aging process.

Since 1979, Tjian has been at the University of California, Berkeley, and in 1987, he became an investigator at the Howard Hughes Medical Institute. He was elected to the National Academy of Sciences in 1991 and has received numerous honors, including the NAS Monsanto Award, the Rosenstiel and Passano Awards, the Louisa Gross Horwitz Award, and this past April, the Alfred P. Sloan/General Motors Cancer Research Award.

The Khoury Lecture is part of the NIH Director's Wednesday Afternoon Lecture Series. For more information, call Hilda Madine at 594-5595.

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