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Spring 2014
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Lady of the Flies
Susan Gerbi fights for the future of science while probing clues to cancer.
It’s the first Friday that feels like spring in Providence, and late afternoon sun streams into Sidney E. Frank Hall for Life Sciences as the campus shifts into weekend mode. A few students are still working in the second-floor laboratory of Susan Gerbi, founding chair of the Department of Molecular Biology, Cell Biology and Biochemistry and the George Eggleston Professor of Biochemistry. Gerbi buzzes between the lab and her office, doing what she does best in the intersecting realms of teaching and research.

“Susan’s lab is always filled with students,” says colleague Kenneth Miller ’70, P’02, a professor of biology. “She’s the sort of mentor who gives full credit to everyone working with her, and she encourages a cooperative and fertile lab environment.”

In the span of an hour, Gerbi cajoles an off-campus colleague to continue a research project, advises a post-doctoral fellow about an experiment he’s conducting under a grant from the Department of Defense Breast Cancer Research Program, and takes a visitor on a virtual tour of her 40-year career in cell biology and scientific thought leadership.

It all happens against a backdrop of concern and advocacy for the future of scientific enterprise.

Bootstrapping

Gerbi arrived in 1972, fresh from graduate work at Yale and postdoctoral training at Germany’s Max Planck Institute. Brown and Pembroke had just merged. The Corporation had just approved the full MD program. And Gerbi’s startup package was a princely $2,500. (She should have known that this was an institution without deep pockets, she notes wryly, when Brown declined to chip in for airfare during her job interview but did offer to pick up her $14.28 bus fare.)

It was a challenging moment in science. The Nixon Administration had frozen federal research funding, and young scientists had to bootstrap their labs. “We got really thrifty,” she remembers. “For instance, we discovered that you can re-use pH paper if you wash it in distilled water.” Despite the arid funding environment, Gerbi’s generation of researchers opened up vistas of new knowledge in basic science.

As time went on, Gerbi became a vocal, national-level advocate for research and graduate education as president of the American Society for Cell Biology and through leadership roles in the Association of American Medical Colleges and the Federation of American Societies for Experimental Biology. Armed with major grants from the National Institutes of Health, National Science Foundation, and American Cancer Society, she became an internationally recognized researcher in ribosomal RNA and in DNA replication. These areas are fundamental to an understanding of cell growth and cell division—work that may benefit people with cancer, a fact that took on special poignancy when Gerbi became a breast cancer survivor a few years ago.


Enter the Sciara

Critical to Gerbi’s work is Sciara coprophila, a fungus gnat that contributes the DNA puffs of its giant salivary gland chromosomes to the research. The International Stock Center for the fly, handed down through a line of researchers since the 1920s, resides in Gerbi’s lab.

“The many unique features of Sciara’s chromosome biology provide terrific models for understanding the underlying molecular mechanisms of the more canonical processes in humans and other organisms,” Gerbi explains.

“Initiation of DNA synthesis is the major check point in the cell cycle,” she adds, explaining that the cell is committed to divide once the genome has been replicated. “We’re using Sciara’s DNA puffs, which represent sites of intrachromosomal gene amplification, to identify specific regions and sequences where DNA synthesis begins.”

To facilitate the inquiry, Gerbi’s team developed Replication Initiation Point mapping to identify the start sites of DNA synthesis at the nucleotide level, and have used the technique to show that—in yeast as well as in the Sciara— the site of initiation of replication is directly adjacent to the Origin Recognition Complex binding site. With that information in hand, they could then explore how Sciara DNA puffs override the cellular controls that permit DNA to be replicated just once per cell cycle. Gene amplification is a hallmark of several types of cancer, but it is not possible to study the initiating event in cancer cells; hence the usefulness of the Sciara DNA puff model system. Preliminary data suggest that ecdysone, a steroid hormone, induces DNA amplification, providing the first example of hormonal regulation of DNA replication. The next question is whether estrogen acts in a similar manner for human breast cancer.

A few years ago, fresh from her own struggle with the disease and immersed in recovering lost momentum in publishing and grant funding, Gerbi purchased a life insurance policy with the Genetic Society of America as beneficiary, providing a fund that would allow it to maintain the Sciara Stock Center for the future generations who will explore its unique chromosome biology and elucidate mechanisms of translational relevance to medicine.

It’s a unique solution, but part of a broad entrepreneurial approach familiar to scientists everywhere. And entrepreneurial thinking is more critical than ever, says Gerbi.


Back to the Future

The funding environment for basic science research has come full circle since she started, Gerbi observes—back to extreme austerity. “We are in crisis,” she says. “There have never been so many consecutive years of a difficult funding environment. It’s affecting people’s careers. Brown has extended its time to tenure by one year in recognition of the fact that it’s so hard for people to get started. So many young researchers are finding themselves with a less full story to tell, due to lack of early funding.”

“The difficulty faced by faculty members in obtaining grants discourages their students from pursuit of a research career,” adds Gerbi, noting that in a previous “grant drought” the percentage of Brown undergrads in Biomed concentrations dropped from 12 percent to 6 percent.

Gerbi fears that a brain drain may occur and that the epicenters of research will move abroad. “It takes a long time to build up know-how in a field,” she says. “[Nobel laureate] Tom Cech, at the University of Colorado, stated in a recent report that it’s not inconceivable that there could come a day, for instance, when we need a new antibiotic for a new disease that’s manufactured by a multinational pharmaceutical company in a country that happens to be at odds with the United States.”

Nobel laureate Craig Mello ’82, SCD’07 hon., P’14—a former student of Gerbi’s now based at UMass Medical School— shares her concern. “There’s a huge amount of pressure on the scientific enterprise, as scientific opportunities outpace federal funding cycles,” he says. “It’s well known that only the top few proposals can be funded in this environment, to the extent that a lot of people aren’t even bothering to apply.”

“Science is the driving force behind our technological civilization, and it moves forward in huge leaps, not at a rate of 2 or 5 percent a year,” Mello continues, noting that funding is especially tight for basic science. “In a very short time, a few decades, we have come from just beginning to probe the basic mechanisms of the cell to understanding fundamental molecular mechanisms of many diseases. While of course we need to spend money on applying discoveries that have been made, we also need to continue to fill the pipeline. Our understanding of basic cellular biology is still very incomplete.”

“Basic science is the engine that leads to fundamental new insights,” he adds. “Failure to fund it adequately, as President Obama said, is like throwing the engine out of a plane and expecting it to continue to fly. On the other hand, not adequately funding translational science is also tragic, as one would fear that new, life-saving therapies might never get tested. To pick up on the President’s analogy, it seems like biomedical scientists are being asked to disassemble the engine in order to build landing gear. And it’s not a good solution.”


Slackers Need Not Apply

Mello was at the dawn of his scientific career when he took the advanced cell biology course Bio 1050—team-taught by Gerbi and Miller—as an undergraduate. “What a pair they were! They were awesome,” he remembers. “One of the things Brown has always done well is emphasize undergraduate education, and we’re fortunate to have really great teachers who bring science to life, who help you get into the minds of the scientists who’ve made the great discoveries.”

“Susan and Ken made it real for you, and put the science in perspective, so that you really understood the human side of the story. I remember leaving class looking forward to hearing the next installment!”

“I’ve taught with Susan since I joined the faculty 31 years ago,” says Miller, noting that Gerbi chaired the search committee that hired him. “I’ve always been impressed by how often and how thoroughly she integrates her own research into her teaching, giving insight into her tools, techniques, and research findings as well as her dead ends. The students really benefit from the fact that they are talking to the woman who’s actually doing or did the work.”

“Susan loves the fact that her course has the reputation of having a heavy workload, which means that it attracts exactly the kind of student that she most loves to teach,” Miller adds with a smile.

For Gerbi, working with students offers immediate gratification as well as hope for the future. “We are blessed to have the students we have at Brown,” she says. “They’re geniuses. It’s fun to work with them.”


Beckman Scholars

Gerbi is the principal investigator on a three-year grant from the Arnold and Mabel Beckman Foundation, awarded this spring, that establishes the Beckman Scholars Program at Brown. Each year, two top undergraduate students will spend a full year pursuing a collaborative research project with a Brown faculty mentor and a co-mentor at the Marine Biological Laboratory (MBL) at Woods Hole, MA. (The University has had a joint education and research program with the MBL since 2003.)

“It’s an extremely competitive grant and a quite prestigious award,” says David Targan, associate dean for science education and director of Brown’s Science Center.

“The grant will enable students to act as links between Brown and the MBL, as they already do at Brown, [forging collaborations] across departments,” he adds. “The Beckman scholars will be engaged in projects over a period of time that is long enough to weave connections that will be sustainable long-term. We think students and faculty at Brown and the MBL will create some very interesting science. We plan to build upon the affiliation, so more students can participate. Beckman students may well go on to become Churchill, Goldwater, or even Rhodes Scholars.”

It’s a critical initiative for Gerbi. “The Program is a wonderful opportunity to stimulate interest in research careers among undergraduates early in their college experience,” she says.

“Susan’s heart is in research and teaching, and from those pursuits come her interests in securing appropriate levels of funding—for research and for training the next generation,” says Professor Emeritus of Neuroscience James T. McIlwain, Gerbi’s husband. “She’s felt a responsibility to make her voice heard in the public arena on their behalf. I think she sees advocacy as her lifelong community service project.”


Eileen O’Gara-Kurtis is the founder and president of Silver Branch Communications and a frequent contributor to Brown Medicine.

Gerbi in her lab.
 
 
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