Just days after moving into his sparkling new lab at Genentech Hall, Joseph DeRisi found himself sprinting down 16th Street in pursuit of an errant FedEx truck.

Inside was a package that few of us would be so eager to receive: gene samples from the severe acute respiratory syndrome (SARS) virus then wreaking havoc in Southeast Asia.

The US Centers for Disease Control (CDC) and Prevention had asked DeRisi, an assistant professor of biochemistry and biophysics, to identify the virus using a technology he had pioneered called a viral microarray. But the FedEx driver couldn't figure out where to leave the CDC's priority package on a Saturday. DeRisi, who had been waiting anxiously at the corner of 16th and Owens streets, finally caught up just before the truck drove away.

Safe to say, it was one of FedEx's more important deliveries that morning in March. As the world now knows, DeRisi and his colleagues, including his postdoctoral fellow David Wang, had an answer for the CDC at noon the following day: SARS was caused by a previously unknown coronavirus. Hailing his work at a news conference on March 24, CDC Director Julie Gerberding, an associate professor of medicine at UCSF who took the helm of the nation's public health agency in July 2002, called DeRisi's microarray "the absolute state-of-the-art probe for viral genes."

The microarray contains representations of 1,000 viral families, including those specific for plants, animals, bacteria and humans. More specifically, it contains 10 to 12 conserved sequences of each of these viruses, for a total of 12,000 nucleic acid sequences on the chip. DeRisi, a self-described "viral hunter," also wants to cure malaria, which he points out, kills millions of people in the Third World but is not the focus of attention by pharmaceutical companies. Using another microarray he developed, DeRisi's team is studying the life cycle of the malaria parasite, to find weak links in its metabolism. The ultimate goal, he says, it to identify drugs that would kill the organism and save scores of lives.

Designed Inside Out

Ten months after the first wave of faculty arrived at Mission Bay, Genentech Hall is living up to its promise as a hotbed of scientific innovation. Designed from the inside out to reflect UCSF's tradition of encouraging interaction between scientists in related disciplines, the building houses programs in structural and chemical biology, molecular and developmental biology, and other fields and is home to UCSF's Molecular Design Institute and the Center for Advanced Technology. Today, the building buzzes with 900 faculty, students and staff, all deeply engaged in creating, through research and support, tomorrow's biomedical breakthroughs.

From her third-floor perch, Cynthia Kenyon directs the Hillblom Center for the Biology of Aging, which supports research on aging, diabetes, neurodegenerative diseases and eye disorders. Kenyon and colleagues are delving into the myriad ways in which two genes, daf-2 and daf-16, work to extend the life span of the roundworm C. elegans. The genes, her lab found, affect the animal's ability to create antioxidants, repair damaged proteins, deter bacterial infections and regulate energy metabolism. A breakdown in these functions is also characteristic of human aging, and so understanding the processes governing them is likely to be fundamental to extending the life span of humans, as well.

On the fifth floor, chemists and chemical biologists work together to accelerate biomedical research and boost the effort to translate research insights into new drugs and other treatment strategies. There, Kevan Shokat, professor of cellular and molecular pharmacology, and graduate student Zachary Knight recently discovered a way to identify the points at which certain important molecules, called phosphates, bind to cellular proteins. This signaling mechanism controls almost every event in the cell, and its failure has been implicated in such diseases as diabetes and hypertension. "Since phosphorylation controls so many biological processes and is involved in so many diseases," says Shokat, "mapping the sites where it takes place will identify many new therapeutic agents."

The 60 labs at Genentech Hall are clustered into research neighborhoods, on the premise — oft proven at UCSF — that scientific collaboration leads to innovation. "Each floor functions as one community, with lots of shared facilities," says Peter Walter, professor and chair of biochemistry and biophysics, who was part of the faculty team that helped guide the design. "The way the labs are built, you can't close the door. You can't hide. You have to communicate."

At this point, it would be hard to stop researchers from talking. Marc Diamond, an assistant professor of neurology who studies neurodegenerative disease, has embarked on three collaborations with colleagues nearby on the fourth and fifth floors. Among them is a project to study compounds that inhibit protein aggregation with Brian Shoichet, an associate professor of pharmaceutical chemistry. "Literally, Shoichet and one of his graduate students just wandered into my office last month, and we started chatting," says Diamond. "It was that simple."

Andrej Sali, acting professor of biopharmaceutical sciences, may soon be the most popular man at Genentech Hall. With the support of IBM and Intel, Sali's group uses 740 computers linked by two servers to model the shapes of proteins and to describe how they evolve. The work is drawing biochemists out of the woodwork. Already he is collaborating with other investigators in the building to define proteins encoded by the parasite that causes malaria and those that ferry substances through the cell membrane.

But Sali also is working on something still more ambitious: a computer-based "pipeline" that takes researchers through the many steps necessary to develop drugs once they have identified a relevant strand of DNA. It could not be done unless Sali had a dozen colleagues nearby who specialize in various stages of drug development.

Says Executive Vice Chancellor Regis Kelly: "If you can couple computers to the pharmaceutical industry, and thereby bring down the cost of drug design and delivery, that would be tremendous advantage to society. We couldn't have done it at Parnassus."

Not to say that the Parnassus campus isn't missed. The five-mile trek across town back-and-forth between the two sites takes its toll, especially for those who teach classes and attend meetings on Parnassus or live a distance from Mission Bay. "But when I get here and I'm walking up that big staircase, it's like walking into a beehive," says Charles Craik, professor of pharmaceutical chemistry who was the first to move into Genentech Hall in January. "It's a working environment in which you know things are going to happen."

Source: Mike Mason

Last updated April 7, 2005

Genentech Hall lab

Laboratory space in Genentech Hall has been designed for efficiency and ease of movement. Photo by Majed.

Genentech Hall exterior

A 100 foot wall of glass graces the front of Genentech Hall, reflecting the travertine stone used on the building's exterior. An outdoor amphitheater near the entrance offers tiered seating for 400. Photo by Majed.