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“There's been this great transformation in biology because of the tools that Roger developed,” says HHMI investigator Susan Taylor, a biochemist at UC San Diego who helped recruit Tsien to the school. They have provided “enormous extra information” about how cells function, she says.
The 2008 Nobel Prize in Chemistry, which Tsien shared with Osamu Shimomura and Martin Chalfie, recognized his work developing green fluorescent protein (GFP) markers to watch proteins in action. By manipulating genes from a glowing jellyfish and from corals, Tsien created a set of genes that produce colors ranging from violet to deep red. These genes allow scientists to tag any of the tens of thousands of proteins at work in the body to observe what they do, and, by marking multiple proteins, how they interact. GFP's utility goes far beyond human biology as well; it's been used to create bacteria that glow in the presence of arsenic, a significant problem in well water in Southeast Asia, and to identify explosives such as TNT.
Tsien isn't leaving visualizing of otherwise invisible processes behind, but he's set his sights on new targets: lighting up cancerous tumors for surgeons and watching memories form. His results on both fronts are promising. At a recent lecture at a Midwestern university, however, when he described his progress, the first question from the audience was about the work he's been trying to leave behind: “When are you going to devise infrared fluorescent proteins?”
At a November science meeting at HHMI's Janelia Farm Research Campus, Loren Looger wanted to set the stage for a discussion of his own research on sensors to study molecular activity in the brain. So the Janelia Farm group leader described Tsien's early work, which focused on calcium.
Calcium is an important cellular messenger that controls neurotransmitter release from neurons, governs muscle cell contraction, and plays a role in fertilization. When Tsien was a graduate student at the University of Cambridge, researchers could measure calcium levels in only a few extremely large cells that could tolerate being poked with a needle. During his graduate and postdoctoral studies, Tsien developed fluorescent dyes to measure calcium in most animal cells without having to inject them.
Later that evening, Tsien gave his own presentation, a last-minute addition to the agenda at HHMI's request, to celebrate his Nobel win. Tsien himself was physically unassuming. Many of the slides were black and white bullet points put together in Janelia's library that afternoon. The presentation's color came from Tsien's passion for his work, a sense of humor about himself, and an interest in others. He explained that he'd decided to speak primarily to the graduate students in the audience.
“I wish to explain how you can screw up and be screwed up and still, some day, accomplish something,” he began.
The first step? “Identify a big problem in biology, preferably one whose solution would assuage a personal sense of inadequacy,” he said. Tsien, who grew up in Livingston, New Jersey, comes from a family of high-achieving engineers—his father was a mechanical engineer and his mother's brothers were engineering professors at the Massachusetts Institute of Technology (MIT). Tsien's brother Richard, originally an electrical engineering major at MIT, is now a prominent neurobiologist at Stanford University and former member of HHMI's scientific review board.
Roger Tsien says that it was a given he'd end up in science, too, but his path to chemistry and biochemistry was in part shaped by his role as the youngest of three brothers in search of his own niche. “Part of the reason [I pursued] chemistry is that it was one of the things that Dad and my brothers didn't really like,” he says. “Dad's idea of taking care of the lawn—since he was an impatient mechanical engineer—was to get on his hands and knees and dig up the weeds. I was allergic to them and wanted to pour herbicide on them from a distance.”
Photo: Paul Fetters