by Robert Sanders
Robert Tjian, a professor of molecular and cell biology who studies the complex machinery that turns genes on and off, has been named a 1994 California Scientist of the Year.
Tjian, 45, was named along with Ronald M. Evans, a professor at the Salk Institute for Biological Studies in La Jolla, who also studies gene expression.
The awards have been given since 1958 by the California Museum Foundation, a non-profit affiliate of the California Museum of Science and Industry in Los Angeles. The two will be honored for their contributions at the 37th annual awards banquet March 8 at the Beverly Hilton Hotel in Beverly Hills.
Both Tjian and Evans are investigators in the Howard Hughes Medical Institutes at their respective universities and are members of the National Academy of Sciences.
Tjian has received numerous awards for his scientific work, including the 1994 Passano Award, the 1994 Rosenstiel Award for Distinguished Work in Basic Medical Sciences and the National Academy of Sciences Monsanto Award for Molecular Biology in 1991. He also is a member of the Academia Sinica, the Chinese equivalent of the academy of science.
Tjian is known for his work tracking down the proteins that regulate the transcription of genes into RNA, the blueprint for production of proteins. Problems with such regulatory proteins are thought to lead to disease, ranging from heart disease and cancer to asthma and immune system disorders.
"The fundamental question is how a cell with 100,000 genes manages to retrieve information at the right time and in the right place," Tjian said. "After decades of research it is now clear which are the important regulatory proteins to concentrate on in terms of treating disease. In the 21st century this is where the activity will be."
His work is founded on decades of experiments in bacteria and viruses which turned up a family of proteins that bind to DNA and tell the transcription machinery--an essentially "dumb" molecule called RNA polymerase--where to start transcribing DNA. The result is messenger RNA, which is read by other machinery to produce proteins that spread throughout the cell to work as enzymes, hormones or structural components.
When Tjian first started working in this area as a postdoctoral researcher in the late 1970s, no one knew whether the same regulatory proteins were involved in mammalian and human cells.
In 1978 Tjian found the first protein, a viral protein, that regulates gene expression in mammalian cells. He and his colleagues have since discovered other regulatory proteins, called transcription factors, that mammalian cells use to fine-tune gene expression. Among these was the first "activator," which binds to enhancers. Enhancers are chunks of DNA upstream of a gene that accelerate transcription when activated.
"...it is likely that therapies of the future will benefit in one way or another from basic research into transcription--research that began not out of a wish to design drugs but rather out of a simple desire to get to the heart of the molecular machinery that controls the activity of our genes," Tjian wrote in the February 1995 issue of Scientific American.
To investigate whether these regulatory molecules are potential targets for drugs, he and two colleagues founded a biotechnology company in 1989 called Tularik Inc., based in South San Francisco.
"The company is a way to take basic information from my lab and others and apply it to practical problems, such as heart disease and cancer," said Tjian, who currently is chair of Tularik's scientific board.
In his work Tjian also has had to develop highly sensitive detection techniques, since many of the proteins he studies are present in extremely minute quantities in the cell. He has found ways to detect quantities as small as a billionth of a gram, compared to the limit of around one thousandth of a gram typical 20 years ago. Several of these techniques, and various reagents required to use them, have been patented by Berkeley and licensed to biotechnology companies.
Tjian was born in Hong Kong in 1949 as his Chinese parents passed through on their way to South America. They eventually settled in Brazil, where Tjian's father, a wealthy industrial chemist from Shanghai, set up a paper mill in the Amazon.
He came to the United States in 1963 to attend high school in New Jersey, entered Berkeley in 1967, and obtained his BA in biochemistry in 1971. After receiving his PhD in biochemistry and molecular biology from Harvard in 1976, he worked as a postdoctoral researcher at Cold Spring Harbor Laboratory in New York until 1979. He then returned to Berkeley as an assistant professor in the Department of Molecular and Cell Biology and achieved tenure as a full professor a mere three years later.
Tjian currently is on the editorial boards of three scientific journals, including Cell, and is a reviewing editor for the journal Science. He also was editor of the journal Molecular and Cell Biology from 1986-89.
He lives in Berkeley with his wife Claudia, a graduate of Boalt Hall, and their two daughters. What free time he has outside the laboratory he devotes to fly fishing, an avocation he approaches "the same way I approach science--with a passion."