Growing up, Anita Sil assumed she would follow in her father's footsteps and become a physician. "I was indoctrinated at a young age," she laughs. "By the time I was three or four, I told everyone that I wanted to be a doctor." But soon after enrolling in a combined M.D./Ph.D. program at the University of Michigan, she knew medicine wasn't the right career path for her. "It's a fabulous profession," she says. "But it was not the thing I was most passionate about."
Her heart belonged to science. "The whole process was really exciting to me," says Sil. "I liked being in control. I could formulate a question, design and execute the experiments, and analyze the data. And I liked that as a scientist, you can become the world's expert on something."
Now at the University of California, San Francisco (UCSF), Sil is one of the world's leading experts on the biology of Histoplasma capsulatum, a fungus that can cause lung disease and blindness. She has laid the groundwork for studying this organism at the genetic and molecular levels, and she has made some tantalizing discoveries about how the crafty fungus adapts to life inside its human host.
Sil discovered her passion for bench science as an undergraduate at Harvard University, where she worked on the proteins bacteria use to build their cell walls. She continued on to get an M.D. and a Ph.D. at the University of Michigan, but, says Sil, "It became obvious during med school that I just wanted to be in the lab."
After spending a summer working at the bench at UCSF, she decided that she never wanted to leave research. She transferred to UCSF and joined the lab of the late Ira Herskowitz, who worked on fundamental questions in yeast cell biology. Yeast, which are single-celled, undergo cell division and give rise to two progeny cells that have distinct behaviors, even though they are genetically identical. As a graduate student, Sil discovered a molecule that is required to specify the asymmetric fate of progeny cells. This type of asymmetric cell division plays a critical role in the development of higher organisms.
Sil completed the Ph.D. program and medical school at UCSF and then became a UCSF fellow—an unusual research position that allows newly minted Ph.D.s to start their own labs. At that point, says Sil, "I really wanted to carve out my own niche."
"I decided to study a fungus whose biology was interesting but not well understood at the molecular level," she says. That fungus was Histoplasma, which lives in the soil in a filamentous form, sending out long tendrils in search of nutrients. Fragments of the fungus can become airborne, and if inhaled by a human, they become rounded and take up residence in cells of the person's immune system.
To study Histoplasma—which because of its infectious nature can require protective masks, gowns, and booties—Sil built the tools she needed to find out which genes are turned on when Histoplasma transitions from the soil form to the host form. To do that, she and her colleague Lena Hwang, then at the University of California, Berkeley, built gene chips—massive arrays of DNA fragments that represent an organism's entire genome—and helped to secure funding from the National Institutes of Health to get the Histoplasma genome sequenced.
Now all that hard work is paying off. In 2008, Sil published two papers identifying genes that allow Histoplasma to colonize host cells and shape-shift from its filamentous form to its globular form—the kind that infects humans. Mutants lacking those genes are always filamentous—producing fuzzy-looking colonies. "Growing what looks like bread mold in your incubator is usually not a good thing," laughs Sil. "But seeing those fuzzy colonies was really fun."
That work has already led to new insights about Histoplasma's lifestyle. "That's what I love about science," says Sil. "You're always learning something new." But science is not the only challenge in Sil's life: "Being a parent is harder than anything I do in lab… It requires a lot of innovation just to get everyone out the door in the morning!"