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FAS Center for Systems Biology Reflects on Two Decades of Research Camaraderie

FAS Center for Systems Biology Reflects on Two Decades of Research Camaraderie

One morning in 2006, then-Bauer-Fellow Kevin Verstrepen was presenting his lab’s work on yeasts and maltose fermentation to the other Bauer Fellows, a small group of early-career scientists who had been hand-selected to pursue interdisciplinary (and often quirky) research topics. He was explaining strange fungal behavior–specifically that yeasts with the FLO1 gene tended to clump together, while yeasts without FLO1 tended to form their own separate clusters–when Kevin Foster, one of Verstrepen’s fellow Bauer Fellows (and current professor at Oxford), leapt up and declared that FLO1 was a “green-beard” gene.

“Green-beard” refers to genes that encode distinct traits–such as hypothetical green beards (or perhaps the stars on star-bellied Sneetches)–that allow the gene’s carriers to identify and cooperate with each other. But Verstrepen didn’t know that at the time.

“I did not understand at all what he was saying,” Verstrepen, who is now a professor at KU Leuven and VIB in Belgium, recalls. “But after he explained the concept of green beard genes in evolution theory, it resulted in a joint Cell paper.”  In that widely cited 2008 paper, Foster, Verstrepen, and their colleagues reported evidence of the FLO1 gene driving “flocculation” or “clumping” behavior in Saccharomyces yeasts, catching the attention of both biofilm researchers and beer brewers who use Saccharomyces.

That paper’s success highlights one of the FAS Center for Systems Biology (then called the Bauer Center)’s greatest strengths–namely, its ability to promote cross-pollination between researchers. “In any other place, Kevin Foster [who primarily studies the “social” behavior of microbes from an evolutionary perspective] would have never seen these results from a genetics lab, and I would have never come across the green beard concept,” Verstrepen says. “They took a risk and gave very young and promising scientists the opportunity to follow crazy ideas. Moreover, they specifically picked people from very different disciplines and with very different research interests.”

After nearly two decades of cultivating top-notch scientific talent and hosting interdisciplinary research, the FAS Center for Systems Biology is passing the baton onto two new initiatives. The John Harvard Distinguished Science Fellowship Program will continue in the tradition of the CSB’s Bauer Fellowship Program by funding research and fostering community between early-career scientists. Meanwhile, the QuantBio Initiative will enable research that uses mathematical modeling and computation to address fundamental questions in biology.

The CSB’s Bauer Fellowship program has had an astonishingly successful run. 25 of the 25 Bauer Fellowship alumni have gone on to faculty positions at universities, including MIT, University of Chicago, Oxford, and UCSF. The CSB itself began in 1999 as the Bauer Center for Genomics–named after Harvard alumnus Charles “Ted” Bauer, whose gift to the university funded the center–but quickly grew into a hub for the emerging field of “systems biology.”

“The Bauer Fellowship turned my path around, and gave me the incredible opportunity to start a new field,” says Bauer Fellowship alumna and MIT Bioengineering professor Katharina Ribbeck. “Charting new territory and getting this research area off the ground required a truly interdisciplinary team of fellow scientists and mentors, who were dedicated to helping each other, [and] a very special team spirit, which is hard to find elsewhere.”

“The Bauer Fellows program helped training a generation of scientists that developed new ways to look at the big picture, integrating genome wide data,” says Bauer Fellowship alumnus and professor at University of Florence Duccio Cavalieri. “The methods and [experimental] approaches [developed] in the early days of genomics and systems biology, are now used to discover predictive signatures for personalized medicine, or for high throughput screening [that are] useful in the development of new therapies. We could say that the Bauer Center worked at developing a Rosetta Stone to read genomics knowledge.”

Many attribute the Center for Systems Biology’s success to the leadership of the Center’s longtime director Professor Andrew Murray. “There is a cliché in scientific circles when discussing the contributions of someone,” says  MCB department chair Professor Venkatesh Murthy. “It’s referred to as the “deletion experiment” – that is, if this person hadn’t existed, what difference would it have made for that scientific field? If I apply this to the CSB, I would say that with Andrew deleted, the CSB would quite simply not have flourished as it has, and it may well have decayed quickly. Andrew’s charisma, care and curation are at the core of the Center’s success, and we will all be forever grateful for his contributions.”

Bauer Fellowship alumni overwhelmingly agree with Murthy’s assessment. “What was inspiring about Andrew is that one felt like he had very little to gain personally by spending so much time on other people,” says MCB professor and Bauer Fellowship alumnus Sharad Ramanathan. “He was very supportive. Any ideas I came up with were taken seriously. No idea was dismissed. So it made you feel like you could do it.”

However, Murray jokes that even though CSB faculty specializing in studying systems become more than the sum of their parts, disentangling which factors were most important is impossible. “My role with the fellows is [to be] like the fairy godmother, I flit into their offices occasionally and chat to them and possibly sprinkle a little bit of fairy dust around.”

Murray is quick to note that leading the CSB has been a team endeavour. When Harvard began planning the Center’s launch in 1999, Murray–then a faculty member at UCSF–was one of their first hires, but he was soon joined by Director of Research Affairs Laura Garwin. In 2007, she was succeeded in the post by Bodo Stern.

In 2006, Professor Erin O’Shea joined the Center and led many of the initiatives that transformed the Bauer Center into the Center for Systems Biology. She has since gone on to become president of the Howard Hughes Medical Institute (HHMI), one of the world’s largest private endowments for scientific research.

At any given time, there were about 10 Bauer Fellows, each running their own small lab on their unique topics of interest. The selection committee took care to recruit fellows with distinctive projects that wouldn’t be absorbed into or overshadowed by existing Harvard faculty labs, because the goal of the Fellowship was to help promising scientists transform into full-fledged lab-runners. Murray likens being a Bauer Fellow to “being a PI with training wheels.”

“There are many fellows programs…but the Bauer Fellows program was unique in that all of the current fellows had labs close to each other, providing endless opportunities for discussion, collaboration, and support,” says Bauer Fellowship alumnus and assistant professor at UCSF Peter Turnbaugh.

The Bauer Fellowship selection committee often chose applicants who would venture into uncharted scientific territory. Murray recalls that when Rachel Dutton applied to the program, her choice of study system stood out. “She came to us proposing to use cheese rind as a novel way to study microbial communities. And she had no experience with cheese,” Murray says. “She’d never worked on more than one species of bacteria at a time. But it sounded like sort of a cool idea, so we and Rachel went for it.” The chance they took paid off; today Rachel Dutton is an assistant professor at UC-San Diego and still uses cheese as a model system.

“Being given the opportunity to start off in a completely new research direction was incredible, but building a research program and team from scratch can be daunting,” Dutton recalls. “What I think set the Bauer Fellows program apart was the quality of the mentoring we received from the program directors as well as the exceptional peer mentoring and sense of community with the other fellows.”

Another fellow who chose to work on an unproven system was Lauren O’Connell. She arrived at the CSB after completing her Ph.D. in the lab of Bauer Fellowship alumnus Hans Hoffman at University of Texas. Hoffman’s research as a Bauer Fellow centered on gathering genetic data on African cichlid fish, so that they could be used as a model organism. “Cichlids were considered a “non-model system” and no genomic resources were available for them at the time,” he explains. “I can say that without my work as a Bauer Fellow, cichlids would still lack model system status.”

O’Connell’s Bauer Fellowship proposal mirrored Hoffman’s in many ways, but she set her sights on bringing an even more unusual creature into the lab–poison dart frogs. “I study how animals adapt to new challenges in their environment by evolving novel behaviors or physiological processes,” O’Connell explains.”We use amphibians as model systems because they are incredibly diverse.” Many programs wouldn’t have greenlit her proposal because O’Connell didn’t have any prior experience working with poison dart frogs, Murray says. But once again, the Bauer Fellowship took a chance that paid off. O’Connell is still studying poison dart frogs as faculty at Stanford. O’Connell says the “freedom to pursue risky ideas” helped her grow as a scientist.

Other fellows were imports from other academic disciplines. Before becoming a Bauer Fellow, Professor Ramanathan had been a theoretical physicist, but he was interesting in learning how living systems use signals. When he became a Bauer Fellow, he decided to focus on yeasts, which are easy to grow in petri dishes, even for physicists who haven’t grown organisms in cultures before.

“He [Ramanathan] came here as someone who had never done an experiment [in a wet lab] and transformed himself into a pretty spectacular experimental biologist,” says Murray.

Bauer Fellows collectively took on a wide range of topics, from the evolution of parental care in amphibians to alternative splicing to immune responses.

Systems biology is notoriously difficult to define, but Murray considers “systems biology” to be more of a mindset rather than a clearly defined field. “If you’re a biochemist, and you’re studying New York City, you just drive around with a taxi driver all day and try to figure out how they turn left and right and avoid running over the pedestrians in New York City as they jaywalk,” Murray muses. “Maybe if you’re a cell biologist, you’re interested in how the diplomats inside United Nations move around. And if you’re a geneticist, you try to figure out what bus drivers do, because you look at New York City when there’s a transit strike, and you see how things are different.”

“And if you’re a systems biologist, you just want to know how New York works,” he says. “You want to understand how the peculiarities of a large global city arise from the interactions of approximately 10 million people, and therefore how the city as a whole has properties that all of its individual inhabitants lack.”

“You could say, ‘Oh, on some level, all of biology is like that.’ But it’s the focus on how the interactions lead to the emergence of general properties that makes systems biology,” Murray adds. Not all of the Bauer Fellows’ research fell within the strictest definitions of systems biology, but Murray developed a reputation as something of a “talent scout” with eye for finding researchers with interesting ideas and extraordinary potential.

“We Fellows challenged each other all the time, we asked hard questions, we supported each other, we spent long nights in the lab together, we partied together, we became friends for life. Every one of us worked on something very different, but we were united in our excitement for the science, our unbound energy, and an open-mindedness,” says Hoffman. “I have not found anywhere else.”

Murray will continue to foster emerging scientists as the Director of the John Harvard Distinguished Science Fellowship. One of the biggest differences between the new fellowship and the Bauer Fellowship is that the John Harvard Fellowship program also includes fellows who study physical sciences, including topics such as star formation and erosion on Mars. But like the Bauer Fellows, the John Harvard Distinguished Science Fellows have weekly meetings to exchange ideas and develop camaraderie.

The Bauer Fellowship experience has also inspired some alumni to launch similar fellowships at their current institutions. “We have recently started a program that aims to foster the same principles at the Broad,” says Bauer alumna and MIT professor Aviv Regev. “Although the research focus is different, we strive for the same spirit of independence, collaboration and community.”

Meanwhile the new QuantBio Initiative, with Bauer Fellowship alumnus Ramanathan and SEAS and Physics faculty Vinothan Manoharan as co-directors, will follow in the CSB’s footsteps by strengthening ties between the life science departments and the physical science departments at Harvard.

Murray argues that the time has come for universities to start new experiments in building scientific communities. “The hope that it’s been an effective model for how to be committed to both research and education and how to live in a community where people are genuinely friendly and supportive of each other but also willing to be rigorous and robust about whether what you just concluded is supported by your experiments,” Murray says. “I think it’s for people other than me to say whether we’ve succeeded.”

Former Fellows

Current Fellows

Andrew Murray faculty profile

Murray lab website

by Diana Crow

Andrew Murray

Andrew Murray