Tracking the Development of the Brain
By Barbara Spector
In vivo studies of Xenopus laevis tadpoles by Hollis Cline ’77 have shown that when it comes to development of the brain, experience counts.
Hollis Cline '77
Cline — the Charles and Marie Robertson Professor and Director of Research at Cold Spring Harbor Laboratory, New York — is uncovering the cellular mechanisms by which sensory stimulation strengthens the connections in the brain. Neuronal activity, Cline explains, enhances development of the parts of the brain involved in that activity via a positive-feedback loop, just as practicing a musical instrument enables musicians to perfect their performance.
“Sensory input can promote circuit development, so the brain is better equipped to process that information,” she says. “This is a fundamental phenomenon in brain development, and also in brain plasticity — the way the brain changes in response to new experiences.”
The Xenopus tadpoles are transparent, so Cline and her team are able to directly observe changes in brain cell structure as animals receive visual stimulation. But there are drawbacks to in vivo studies, she notes. “When you are working in vitro, you can design a very specific experiment,” she says. “With a live animal, you can’t possibly control all the variables, so you have to be much more open-minded when you assess your results. The experiment might actually reveal something you weren’t expecting — but that’s part of the fun of it.”
Cline’s team studies neuronal development via time-lapse imaging, which “allows us to see developmental changes that are basically invisible by other methods,” she says. The movies generated from these time-lapse images have uncovered a surprising finding: While new branches are continually added to neurons, they are also constantly being retracted in a trial-and-error process. “That would have been impossible to see without time-lapse imaging,” Cline says.
One potential outgrowth of these studies involves investigating which genes and proteins are required for enhanced neuronal activity. Such basic science investigations could have relevance for medical disorders such as mental retardation, including fragile X syndrome, learning disabilities and cognitive deficits, Cline notes.
Cline, who has been at Cold Spring Harbor Laboratory for 10 years, oversees an international lab team. “I try to promote the multicultural aspect of working together,” she says. “One of the perks of science is that it draws a diverse group of people.”
Another advantage of working at Cold Spring Harbor Lab, she says, lies in its small size. There are only about 45 principal investigators at the institution, she notes. “With such a small group, it’s easier to interact with everyone, and I can learn a lot about their work.”
Cline, who became Director of Research at Cold Spring Harbor Laboratory in 2002, says she enjoys her new mentoring and fundraising responsibilities. “I get to help the junior faculty figure out how to direct their research programs and help them strategize about research funding,” she says. One of the institution’s main objectives, she notes, is to ensure that young faculty members become leaders in their field. She adds that she relishes fundraising activities because “I get to meet a lot of different people who have different motivations for their involvement in scientific research.”
Her Bryn Mawr experience helped her to develop the skills to communicate with people of all backgrounds, Cline says. “Because the classes at Bryn Mawr, for the most part, were all women,” she notes, “we acquired the confidence to develop our ideas and speak out.” Cline recalls another advantage: “We had excellent laboratory training. I didn’t appreciate it at the time; it just seemed normal to me.” Later in her career, when she began interacting with undergraduates from other institutions, Cline realized that “they didn’t have a clue about how to do any kind of practical work in a laboratory — or the theoretical principles of experimental design.”
After a few years as a technician at the Memorial Sloan-Kettering Cancer Center, Cline attended graduate school at the University of California, Berkeley, where she received her Ph.D. in 1985. Her thesis adviser, Gunther Stent, encouraged her interest in the plasticity of the visual system. “I was interested in developmental neuroscience because it could be carried out in a quantitative, controlled way,” she says. At Berkeley, Cline met her husband, Robert Malinow, also a neuroscientist. They both ended up as postdoctoral fellows at Yale University ; they then moved to Stanford University, where each did a second postdoc. They later both became assistant professors in the Department of Physiology and Biophysics at the University of Iowa. After three years in Iowa, a colleague recruited them to Cold Spring Harbor Laboratory.
Today, they are the parents of a daughter, Rose, 14. “We made the decision when I became pregnant that we would go home at six and have dinner as a family. We decided to confine our work to the weekdays and restrict our work-related travel to once a month,” she says. Making time for the family “makes you a bit more organized and forces you to set priorities,” Cline says. “Although many women are still concerned about this, in my experience, it is no longer true that a rewarding family life and career are incompatible.”
Barbara Spector writes on science and technology as well as business topics. She is the editor-in-chief of Family Business magazine and former editor of The Scientist.