Ask Charles Zuker how he got into researching how we taste, and he'll tell you it was driven by his desire to decipher how the brain represents our sensory experiences. Zuker wants to do more than understand why sugar is sweet. He wants to know how the brain can turn reception into perception. How do the physical and chemical stimuli that we take in all the time—through sight, hearing, taste, touch, and smell—turn into signals that neurons transmit to the brain? How does light hitting your eye change into a chemical signal that makes you squint? How do sound waves hitting the eardrum transform into words that you "hear" in your head? Why does a drop of lemon juice on the tongue make you wrinkle your nose?
Zuker and his laboratory have made advances in the understanding of sight and hearing. They've also discovered taste receptors for four of the five tastes: sweet, sour, bitter, and "umami" (savory). Salt is the fifth, and it's only a matter of time before Zuker tracks it down.
Perhaps more important than just discovering the receptors is Zuker's research showing that each taste cell is hardwired for one taste. Scientists used to think that every taste bud could pick up on all five tastes, and that a different signal would be sent to the brain for each one. Zuker's lab did experiments with mice that proved that taste cells are simpler than that. Each taste cell has receptors only for one taste modality. And each cell sends a specific signal to the brain. This signal doesn't change, even if you swap out one receptor for another. For example, you can remove the receptor from a "sweet" cell and replace it with a receptor that's normally activated by a bitter chemical, and now "bitter" tastes sweet.
This research has obvious commercial implications—for example, what if we could find ways to reduce our "dependence" on sugar and salt, two key food ingredients that have a significant impact on our well-being? In 1999, Zuker started Senomyx, a company that looks to identify novel flavors and taste enhancers for the food and beverage industry. "It's interesting to work on something that could ultimately [improve] human health and perhaps help enhance our human sensory experience so we can get more joy out of life."
But not work on just anything. In Zuker's mind, scientists should not only do good science but also solve tangible questions. "We could just do fun experiments, but those might not lead to answers that help us move forward," he says.
Zuker's grandparents moved to Chile from Poland and Russia to escape the Holocaust. As a child in Chile, Zuker loved microscopes the way some boys love Legos. "I played with a microscope from the time I had coordinated movements," he says. "For my bar mitzvah, when I was 13, I got a binocular microscope. For the first time, I could look at minute things with both eyes. That opened up a whole new world."
Zuker went to college at 16. At 20, he started graduate school at MIT. By 26, Zuker had his PhD and was a postdoc in Gerald Rubin's lab at the University of California, Berkeley. (An HHMI investigator since 1987, Rubin is now director of HHMI's Janelia Farm Research Campus.) He then took a position at the University of California, San Diego, where he has been since 1986.
His lab is a mix of think tank and traditional. About half the lab focuses on a specific problem; the other half consists of what Zuker calls "rogue scientists"—people working on their own questions.
"These people come here with a visceral need to solve something they want to solve, rather than coming here so I can tell them what I want them to solve," he says. This has led to a diversity of work, including a paper on the evolution of fly eyes (Nature 12 October 2006) that showed that one protein, called spacemaker, is a key element in the evolution from ancestral insect eyes (and those of modern bees) to the more complex modern eyes of fruit flies and house flies. Without the protein, an eye is more primitive; add the protein, and help it transform into a modern eye. "It's very exciting," Zuker says of the results.
Letting people do their own thing comes easy to Zuker. He has always followed his bliss. "Research is not a career for me," he says. "It flows in my veins. It is not by choice; it is who I am."
Dr. Zuker is also Professor in the Departments of Biochemistry and Molecular Biophysics and of Neuroscience at Columbia University College of Physicians and Surgeons.