Wilma Lingle's eyes light up when she talks about -- well, just about anything. "I want to learn how things work and how things come together, not just on a biological level," she says in an interview with Science Careers. Lingle, who is now a breast cancer researcher and core-facility director at the Mayo Clinic in Rochester, Minnesota, adds, "How do you do the logistics of getting something from the patient to the laboratory? It's a very similar thing with the cell. You have to have this protein here and then this happens and this happens. It's all a pathway. It's putting the pieces together so the pathway works."

Lingle's own pathway hasn't been straight, but the pieces have fallen into place, and it works. She has moved from studying bioluminescent fungi to protozoans, then on to breast cancer. Today, she produces original breast cancer research while managing two core facilities at the Mayo Clinic.

Glowing fungi

Lingle was still a child when she began to swipe the biology textbooks her sister, 9 years her senior, brought home from college. "I didn't know what I was reading, but I was looking at the pictures. I loved the microscopy," Lingle says. That exposure to biology led her to pursue an undergraduate degree in plant pathology and a master's in botany at the University of Georgia (UGA) in Athens, where she studied fungi. At each level, she says, she realized she needed a still-higher degree to do what she really wanted to do.

Eventually, she received a Ph.D., also from UGA, studying why certain mushrooms are bioluminescent and others aren't. Her research led to the discovery that mushrooms that glow can break down lignin, a compound found in wood, and those that don't, can't. The luminescence, she learned, is a direct result of the process by which the mushrooms break down lignin.

After she had worked as a postdoc for a few years, her husband, who studied bioluminescent bacteria, was hired at the Mayo Clinic. Lingle followed him there, though she wasn't confident about finding a place for herself -- a mushroom specialist -- at the medical institution. "When you are in school as a botanist or mycologist, you have to learn biology tools," she says, but she didn't know much about human biology. So she looked close by. "I knew some mycologists at the U of M" -- the University of Minnesota, Twin Cities, a 90-minute commute from Rochester -- "and was putting out feelers for things to do. And I didn't find anything."

Soon after arriving in Rochester, however, she was introduced to Jeffrey Salisbury, a Mayo researcher with a background in botany who was studying the role of centrin in cell division. When somebody brought Lingle and her husband to meet Salisbury, "we got into a conversation about bioluminescent fungi," Salisbury says. "We had this animated conversation." Lingle started working in Salisbury's lab, studying a protozoan that lives in the hindgut of termites and makes more centrin than anything else in the world does. "I had a termite colony in a desk drawer," Lingle says. "When I wanted to do a study, I would have to get the protozoans out of the termite's hindgut and do my studies really quickly."

Lingle and Salisbury went on to demonstrate that centrin plays a crucial role in cell division (here and here), and that centrin overexpression is associated with cancer (here and here). Around that time, Salisbury and his wife started a graduate-level tumor-biology program at Mayo. Lingle signed on to teach the classes, but she was always just "a step ahead of the students," she says. "It was essentially like another Ph.D. in biology. That was great."


Wilma Lingle (CREDIT: Courtesy, Wilma Lingle)

“Stunning images”

The centrin work provided a bridge into human biomedicine, and eventually she applied for -- and received -- a career development grant from the Department of Defense to do breast cancer research. She started an independent project in the lab of Patrick Roche, the director of Mayo's Tissue and Cell Molecular Analysis (TACMA) facility. When Roche left, Lingle was offered the directorship of that facility.

Meanwhile, more Department of Defense grants allowed Lingle to establish her own lab, focusing on centrosome amplification in the development of cancer. Lingle’s lab has published papers showing that larger or more numerous centrosomes are correlated with chromosomal instability, and thus breast cancer. She has also studied signal adapter proteins’ role in cancers, and looked at the role that certain gene mutations play in a patient’s response to chemotherapy.

The TACMA facility processes cell tissue for researchers around the world who are conducting studies on any number of diseases. Lingle oversees staff members who create digital images of tissue microarrays, fitting hundreds of samples on a single slide and making the resulting images available to researchers worldwide.

This focus on imaging doesn't surprise Salisbury, her former mentor. "Some people can look in a microscope and see absolutely nothing," Salisbury says. "Other people can look through a microscope and make images that make other people see what's there. Wilma's one of those people." Salisbury adds that the images of termite protozoa and centrosome abnormalities Lingle produced in his lab, were "aesthetic and pleasing" in addition to being instructive. "She was able to put together really stunning images."

About 10 years ago, Lingle was invited to co-direct another Mayo facility, the Biospecimens Accessioning and Processing (BAP) lab. At BAP, now a sprawling facility that covers several rooms across multiple buildings, Lingle co-supervises tens of technicians who process and store tissues for studies. She and her staff are developing a biobank of blood samples from Mayo visitors who are not seriously ill; researchers will use these samples as controls in their studies. The lab also handles, processes, and stores samples for more than 600 current studies.

The core-facility work takes up less time than one might assume. "One of the best things about these two labs," Lingle says, "is I have great supervisors and great managers. They take care of the day to day things." Indeed, Lingle considers her ability to find and train independent people to be a particular and important strength of hers. "I have an open-door policy, but most of the people that work with me are pretty independent. And if they don't start out independent, I try to train them to be more independent and discover their own skills," she says. "You have to be able to recognize when people are ready to run on their own," she says. As a consequence, partly, of these efficiencies, she still has time to run an active research lab.

Reinvention

Over the course of her career, Lingle says, "I've reinvented myself as a scientist two or three times. It's always been fun each time to go into a new area and explore it." She urges young scientists -- especially those who might feel like they're becoming pigeonholed -- to "take advantage of whatever opportunities you have. If you have an opportunity to learn something, go for it."

Rachel Kaufman is a freelance science writer living in Washington, D.C.

Rachel Kaufman is a freelance writer living in Washington, D.C.
10.1126/science.caredit.a1100076