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Stanford Report, June 14, 2000

Stanford Genome Technology Center open house draws crowd  

BY KRISTA CONGER

Scientists, engineers and members of the public mingled over snacks and high-tech sequencing machines last Friday at the Stanford Genome Technology Center on Palo Alto's California Avenue. The crowded open house commemorated the near-completion of several large-scale sequencing projects and spotlighted the center's next big goal ­ understanding the function of the genes they've worked so hard to sequence.

"Finishing all of these different projects means that we now have an opportunity to move in a new direction," said Ron Davis, PhD, director of the center. To emphasize the switch in focus from determining DNA sequence to understanding the function of the new genes they've identified, the center has recently changed its name from the Stanford DNA Sequencing and Technology Center to the Stanford Genome Technology Center.

According to Davis, a professor of biochemistry at Stanford, center staff members were also hoping that the event would raise awareness both on and off campus of the center's work and perhaps stimulate productive research collaborations and technology transfer.

"We've realized that many people don't know that we exist," said Davis. "This may be partly because we don't have a building on campus, and partly because we've been very busy doing a big job."

The big job has included participating in an international effort to sequence the genome of the small plant Arabidopsis thaliana and shotgun sequencing of the entire 16 megabase genome of the yeast Candida albicans, as well as participating in the human genome project. Along the way, center staff members, which include biologists, engineers and software designers, have designed and built some of the most sophisticated robotic sequencing machines around. The new technology has enabled faster, more efficient DNA sequencing, with an error rate of only about one base per 10,000 bases.

"DNA sequencing at the Stanford Genome Technology Center is two to three times more cost efficient than most other sequencing centers nationally," said Lane Conn, production manager for the center. "This is an outgrowth of our automation development."

Indeed, the technology on display last Friday would make nearly any graduate student drool. Robotic plasmid prep machines have the capacity to isolate more than 1,100 of the small circles of DNA from bacterial cultures in only 12 hours. Automated sequencing machines can crack the nucleotide code of more than 300 samples in the same time period. Now the center is ready to apply this technology to the relatively new field of functional genomics.

"The sequence itself is an achievement, but figuring out what it all means is what will go on for years and years," said Nancy Federspiel, PhD, head of the Arabidopsis project. Researchers at the center have been working for four years to sequence a portion of the plant's chromosome 1. Sequencing of the entire genome, which is expected to be completed by the end of the year, is the result of international collaboration. Completion will mark the first time that a plant genome has been entirely decoded.

"It's really cool to have a representative genome from another kingdom," said Federspiel. Although Arabidopsis is used mainly for scientific study, similarity between plant genomes means that the completion of the Arabidopsis sequence may have important implications for agriculture, said Federspiel.

Federspiel, an associate director of the center, also headed the effort to sequence a portion of the genome of the yeast Candida. Candida usually causes only mild infections in healthy people, but it can be very dangerous to immunocompromised individuals, such as HIV infected people or transplant patients receiving immunosuppressive drugs. According to Federspiel, analysis of the sequences of both strands of Candida may identify particular genes that are responsible for the increased pathogenicity of certain strains and pinpoint weaknesses in the fungal lifecycle that may be susceptible to new antifungal drugs.

In addition to the sequencing projects, center staff members have also been participating in an international effort to disrupt nearly 90 percent of the genes in the yeast Sacchromyces cerevisiae. By creating individual strains that are each missing one gene, scientists hope to be able to determine what the missing genes do. Currently, the function of about 30 percent of S. cerevisiae genes is unknown.

Davis and other Center staff were glad to see Stanford scientists as well as representatives from local biotechnology companies, UC-Berkeley and UCSF, high schools and law firms, crowd around posters describing the various research projects and trod on each other's toes during the tour of the facilities.

"They are always welcome," said Davis, of the visiting scientists before the event began, "but they may need a reason to come. Hopefully this open house will help us generate interest and spark new collaborations."

The National Human Genome Research Institute has funded the center, which is one of the National Institutes of Health genome centers, since 1993. For more information about the Genome Technology Center's ongoing projects, visit www-sequence.stanford.edu. SR