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Breaking New Ground Targeting Malaria 10.20.03 ![]() Given the groundbreaking work that goes on inside, it’s fitting that Genentech Hall stands at San Francisco’s newest frontier. The first of 20 buildings planned for the 43-acre site at the city's eastern waterfront, the 6-story building of Italian travertine stone opened in January 2003. Gleaming laboratories, divided into North and South across a carpeted spine, are organized into “neighborhoods,” where sets of laboratory bays fan out from a central hub of offices and a kitchen commons. On the south side, overlooking the Caltrain semaphores at 16th Street and Mississippi, is the DeRisi lab. In the tissue culture room, Joe DeRisi, PhD, assistant professor of biochemistry and biophysics, gingerly reaches under the flow hood for a small acrylic container of cherry-colored blood infected with malaria. It’s his blood. Lab workers look over his shoulder at the gelatinous sample and teasingly speculate what he must have eaten for dinner the night before. It’s a congenial group, amused by the celebrity that has brought national journalists and network news crews to the fourth floor lab. Urgent package from Atlanta In March 2003, DeRisi took a weekend out from his malaria work to respond to the Centers for Disease Control (CDC), and apply the microarray technology he developed to find clues to a mysterious virus taking hold in Asia. At a CDC news conference that month, Director Julie Gerberding, MD, told the international crowd that DeRisi’s microarray represents “the absolute state-of-the-art probe for viral genes.” DeRisi had refined the technique only weeks before, while preparing to move his lab to Mission Bay. Before opening the CDC’s FedEx package, DeRisi prepares a slide with samples of DNA sequences from all known completely sequenced viruses – a grid of 12,000 microscopic dots filling a conventional one-by-three-inch glass slide. He laces the mystery virus with a florescent agent that will light up wherever on the grid the sample finds its genetic match, and puts the slide in the scanner. Next, lab workers surround the computer as the screen displays the dotted readout, like a futuristic version of a child’s LiteBrite pegboard. What DeRisi describes as his “Eureka moment” came when a glance at the dayglow field of unknown samples clearly identified a new virus. It told him that the culprit responsible for severe acute respiratory syndrome, now familiar as SARS, was a coronavirus, with links to the common cold and similar viruses in animals. The clinical implications became immediately apparent: containment, quarantine, isolation and negative-pressure rooms. New malaria targets Hailed in the press as a “virus hunter” and “gene jockey,” DeRisi earned his doctorate at Stanford University under renowned biochemist Patrick Brown, PhD, who developed some of the earliest microarrays. But it was another professor, Pradip Rathod, PhD, raised in Africa, who suggested using the technology to tackle a problem like malaria. “Since the malaria genome was being sequenced, it was a perfect opportunity to apply what we’d done,” explains DeRisi. “I said, lay it on me.” Malaria kills up to two million people a year, most of them children in sub-Saharan Africa. It was better controlled 20 years ago than it is today, as resistance has developed to drugs used to treat the disease and as educational and eradication efforts have faltered. DeRisi’s goal is to develop cheap, non-toxic, anti-malarial drugs using microarray technology. His team is on the brink of releasing the latest high-resolution data, that will provide dozens of new drug targets, vaccine targets, a first-step screen, and ample other leads. While other investigators might aim to publish their findings exclusively
in the most prestigious journals, DeRisi strongly supports open access
Internet journals and puts his research out on the Internet. |
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