This petri dish holds over a thousand C. elegans nematodes, the tiny worms that Judith Kimble uses to analyze the biochemistry and cell biology of stem cell regulation.

That 1981 discovery alone would have earned her a solid place in any history of developmental biology, but in the decades since she has made it her foundation for investigating the molecules that help stem cells “choose” which daughter cells they will form. Should they make more copies of themselves, enter the irrevocable process of differentiation, or go 50/50 and make one stem cell and one specialized cell? A stem cell in the germline (which contains genetic material that can be passed to offspring) faces similar decisions: whether to reproduce itself or to undergo meiosis—reduce its number of chromosomes by half and produce, after another decision, a sperm or an egg.

By observing one giant cell in a tiny worm, Kimble invented a “lens” for the study of stem-cell regulation, says HHMI investigator Geraldine Seydoux, who studies germ cells in the nematode at the Johns Hopkins University School of Medicine. “She established the germline of C. elegans as a model system for the study of stem cells and stem-cell renewal. She was so much at the forefront that few people at the time realized the implications of her work. They did not understand what could be learned from a tiny worm.”

Kimble, at Wisconsin since 1983, and an HHMI investigator since 1994, explains that her research interests have always been driven by curiosity about the control of development—and C. elegans was a useful means to that end. But these pursuits also have an eminently practical side: defects in stem-cell regulation may lie behind a variety of developmental diseases, cancers, and even aging.

Yet Kimble's enthusiastic curiosity extends beyond the lab. Outgoing, gregarious, and self-confident, she will (sometimes) shelve her in-flight routine of scientific editing for a chance conversation. En route to a recent HHMI conference in Lisbon, for example, she found herself deep in discussion with Bright Sheng, a Chinese-born composer whose work has been performed by Yo-Yo Ma and the New York City Ballet.

“He had a theory that the structure of music was somehow a reflection of the structure of your brain; that what we find beautiful in music is beautiful because it reflects the structure in the brain,” she says. “I was not convinced this was right, but it was a beautiful idea, and the two-hour flight went fast.” He offered her a ticket to the Gulbenkian Orchestra, which was showcasing one of his new pieces. But she and her HHMI colleagues were already scheduled to attend the concert, which Kimble says, “was a pinnacle experience.”

Photo: Kevin Miyazaki

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