An undergraduate team of emerging synthetic biologists from Brown and Stanford prepares to culminate a global competition this weekend after a productive nine months advancing the science of an entirely biological balloon.

PROVIDENCE, R.I. [Brown University] — It’s tempting, but wrong, to think of the 20 minutes on Oct. 28 when a team of Brown and Stanford students presented its entry to the judges at the International Genetically Engineered Machines Giant Jamboree as a defining moment. In fact, though the group’s brisk summary of nine months of work will figure prominently into how they are rated among the contest’s hundreds of teams, that presentation will reflect only a sliver of the significance of their endeavor.

That doesn’t mean, of course, that the students don’t want to pick up a medal or two in Boston this weekend [Editor's note Oct. 31: They won 'Best Measurement' and were runners up for "Best Manufacturing']. But what they value much more deeply is the experience and the potential impact of the work they have undertaken since February. Their mission was to lay the scientific groundwork for an entirely biological balloon that could be generated for atmospheric explorations of other planets, like Mars. Think of an environmentally sensitive weather balloon that a robot or astronaut could grow on site and on demand from small cultures of cells.

So what have they accomplished? Among many other things, the team has filed a provisional patent for making E.coli bacteria produce latex rubber. They’ve coaxed microbes to produce hydrogen gas (for balloon inflation) and successfully tested color-changing, temperature-sensing proteins high up in the atmosphere. After a crash course at NASA’s Ames Research Center in California, they’ve become skilled practitioners of the craft of synthetic biology, in which engineers endow cells with new capabilities by swapping modules of DNA instructions into their genomes.

This weekend’s presentation and poster session was, therefore, just one more milestone in a string of experiences that started months ago and may continue for months or years after the Jamboree. Notably, although their project is new, they are building on the work of prior teams. Future teams, in turn, can build on theirs.

“Our team is building on a legacy of years and years of projects,” said Brown junior Taylor Pullinger, who is studying biotechnology and physiology. “A lot of the work that we’re doing is proof of concept, but in the future all of those pieces could really come together into finding real solutions. One of the things about being in a lab at NASA is you see the work that’s being deployed. It was really cool to be able to place our work in context.”

Continuous innovation

The Massachusetts Institute of Technology launched the iGEM competition in 2004, and Brown first joined in 2006. Professor of Biology Gary Wessel, who remains an advisor, marshaled the first several teams before adjunct professor and alumna Lynn Rothschild (PhD ’85), an astrobiologist at Ames, took the helm in 2011 and established the partnership with Stanford. Now, six students from each school join forces annually to embark upon an odyssey of innovation catalyzed by the competition and inspired by bioengineering’s experimental value to the space program. Along the way, the team has also received advice from Jim Head, Brown’s Louis and Elizabeth Scherck Distinguished Professor of the Geological Sciences, on real-world space applications related to projects and support from the NASA Rhode Island Space Grant Consortium.

“This is a way to do proofs of concept — to show what’s possible — and to do it with a lot of creativity,” Rothschild said. “It’s so much fun to try new things to see where they are going to lead.”

In prior years, teams have pursued projects, such as a biologically based way of making cement for construction on other planets, and developed a biological sensor that will be launched on the European EuCROPIS satellite in March 2017.

Stanford-Brown teams have developed new synthetic biology capabilities used by subsequent teams. The current team, for example, made the color-changing, temperature-sensing proteins by advancing discoveries the 2015 team made in the course of developing self-folding biological materials. That team tinkered with pigment genes from coral. This year’s team discovered and characterized novel color-changing capabilities in similar chromoproteins in a sea anemone and realized that the way they changed at different temperatures could be useful for atmospheric sensing.

A central tenet of the iGEM experience and community is the development, documentation, demonstration and dissemination of standardized snippets of DNA code called “biobricks,” said team member Eric Liu, a sophomore studying applied math and computer science. This year the Stanford-Brown team is using nearly 50 biobricks — some borrowed, some created — in developing its balloon technology.

“iGem is like the open-source software of the synthetic biology world,” said Elias Robinson, a junior concentrating in computational neuroscience. “You are contributing to the field as a whole. If later teams want to research anything similar to what we’ve done, they can much more easily do it. Each year, the team’s work will be easier because of the work other teams have done previously.”

To be clear, this year’s team hasn’t made a whole bio balloon. Instead it’s created — mostly over two summer months at Ames — many technologies to enable one. But even if one is never made, innovations such as the now patent-pending bacterially made latex could be a substantial contribution. Two industrial sources of rubber and latex are huge plantations or synthetics derived from fossil fuels. Rubber grown from bacterial cell culture, which use genes inserted from the trees, could reduce land use and carbon-rich resource extraction. When the team presented the idea at the New York Maker Faire in September, they won a blue ribbon for sustainability.

The invention seems like an unlikely feat for 12 undergraduates, many of whom had just learned synthetic biology, to accomplish in months, but Pullinger and Cynthia Hale-Phillips, a biomedical engineering senior, attribute it to the versatility of synthetic biology and the freedom to just try stuff.

“It’s one of the advantages of being a rag-tag group of undergrads,” Pullinger said. “We’re not tied up in the bureaucracy of being a large rubber company. We’re kind of like, ‘Why not? Let’s give it a go.’”

A 'rag-tag' group of undergrads
From left to right (Stanford (S) and Brown (B): Elias Robinson (B), Taylor Pullinger (B), Theresa SIevert (S), Anna Le (S), advisor Lynn Rothschild, 
Taylor Sihavong (S), Amy Weissenbach (S), Cynthia Hale-Phillips (B), Charles Gleason (B), Julia Gross (B), Eric Liu (B), Michael Becich (S), and advisor Kara Rogers.
Image courtresy Lynn Rothschild

As Hale-Phillips put it, “We can try crazy things — sometimes they work.”

There are the technologies themselves and then there are the educational and even career opportunities the experience creates. Past Stanford-Brown teams have generated research projects that have turned into theses — Hale-Phillips is completing her senior thesis by continuing some of the work of the 2014 team. Two former team members have returned to Rothschild’s lab to work with her at Ames.

Another important component of each project is consideration of its human and ethical implications. For instance, this year’s team members have been interviewing leading thinkers about space exploration and astrobiology, including renowned astronomer and researcher Jill Tarter. Their discussions of topics such as growing life on other worlds have become a series of podcasts.

Cross-country collaboration

In its totality, iGEM is a year-round venture. About now, as the current team reaches the milestone of the competition, next year’s team members are preparing applications in hopes of making the cut. Last year, for example, 36 Brown students applied for the six available slots. The students are supported by Undergraduate Teaching and Research Awards.

By February, when the Brown and Stanford participants have been determined, the students begin planning by videoconference. This year, Rothschild suggested the bio balloon idea; but from there, the students ran with it in regular meetings with her advice along the way.

On June 1, the ideas become action when the Brown team flies out to Ames for the summer. While their Stanford teammates are still in school for a few more weeks, the Brown students take their crash course in lab techniques and then get to work.

“I don’t think any of us from the Brown side had really done synthetic biology approaches before we got to the lab at NASA,” Hale-Phillips said. “Some of us had lab experience, but in terms of cloning into bacteria and all these different techniques, we learned them in the first couple of weeks and then we could use them the rest of the summer. Now we can apply it forever.”

Then they get to work on trying to implement their concepts and plans in the lab — inserting biobricks into tiny organisms and running experiments. In one of many summer highlights, the team hooked up with the Stanford Space Initiative to fly the temperature-sensing microbes up to 70,000 feet.

From late June when the Stanford students join in, through Labor Day when the Brown students return home, they work together at Ames. Students focus on areas that interest them most, but they assist each other as well. After all, biology is full of downtime as cell cultures incubate and grow or newly ordered biobricks are being synthesized and shipped to the lab.

After the Brown students return to Providence, the Stanford students keep working at Ames, but that doesn’t mean the Brown team goes idle. In addition to the appearances in Boston, another major component of the team’s score is the team wiki, which had to be developed to its fullest extend and then locked down on Oct. 19. In addition to getting that prepared, Brown students also focus on theoretical work during the fall. Liu, for example, worked on modeling bacterial metabolism to optimize their productivity for making the team’s products.

This week, the Stanford students fly in for a series of high-stakes rehearsals and then the festivities in Boston. The team typically does very well, but that assessment rightfully goes beyond medals and ribbons to include things like provisional patents, thesis projects, new biobricks, satellite payloads, new bioengineering skills and professional connections — not to mention new friends and potential colleagues for the decades ahead.