Yale team to showcase its science research in an international competition

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Some of the members of the Yale iGEM team and their mentors are pictured here. They are (front row, from left) Kara Brower ’13, Durga Thakral ’12 (holding the computer featuring Darren Zhu ’14 on Skype), and graduate student Jen Nguyen. Back row, from left: graduate students Adam Trexler and Dan Spakowicz, and team leader Aaron Hakim ’13. (Photo by Michael Marsland)

Over the past six months, a team of undergraduate scientists has learned firsthand that fierce competition and friendly collaboration sometimes combine in winning ways.

In fact, the students discovered, the mix sometimes results in the most successful outcomes where scientific research is concerned.

On the weekend of Nov. 5 & 6, the Yale team will participate in the International Genetically Engineered Machines (iGEM) Competition, in which undergraduate teams from around the world vie for top-place honors for their synthetic biology research. Already selected as a grand finalist in North America — outdoing groups from such schools as Harvard, the University of California-Berkeley and the Massachusetts Institute of Technology (MIT) — the team is one of just four regional finalists, chosen out of 64 university teams from the United States and Canada. The iGEM world championship round is held at MIT.

A major discovery. For its iGEM project, the Yale team synthesized an “antifreeze” protein isolated from a cold-tolerant beetle called Rhagium inquisitor, which is found throughout Europe and in even the coldest parts of Siberia. During the summer and earlier this fall, the team produced the protein using the bacteria E. coli as a host, purified it in large quantities, demonstrated function of the protein through a variety of assays, and began analyzing the protein’s structure and optimizing its activity. To accomplish this, the students honed their skills in such synthetic and molecular biology techniques and processes as cloning, gene expression, purification, chromatography, X-ray crystallography, and multiplex automated genome engineering, among others.

The undergraduates’ project may revolutionize the way food is kept frozen, how transplant organs are refrigerated without damaging healthy tissue, or the way airplanes are de-iced, among other applications, the students say. It may even be used to help extend crop growing seasons.

“The antifreeze protein we developed binds to ice and stops it from forming large ice crystals,” says team member Durga Thakral ’12. “While other antifreeze proteins — which often come from fish or other animals — are already used, such as in the ice cream we eat, ours is actually more effective in inhibiting ice crystal growth.”

This is only the second year that Yale has participated in iGEM, which was launched in 2003. Thus, the research accomplishments of the students are particularly remarkable, says Dorottya Blaho Noble, the assistant director of the Raymond and Beverly Sackler Institute for Biological, Physical, and Engineering Sciences at Yale, which promotes transformative, interdisciplinary research and teaching initiatives on campus and is one of the main sponsors of the team.

“We couldn’t be prouder and happier for the team’s success,” Noble comments. “To compete in iGEM, the undergraduates have to figure out what would make a feasible project — one that could have importance to the community and to the world — and then carry it through successfully. The competition offers a rare opportunity for undergraduates to design and conduct their own scientific research. It requires innovation, hard work, motivation, and dedication. The team is a small one, but its members took advantage of good mentoring and support from graduate student scientists and faculty members, who gave generously of their time and sometimes their lab space. The team’s project has huge potential, and we are excited to see how it does in the competition.”

Ideas to innovation: Yale’s team members began thinking about their project in February of last year, led by junior Aaron Hakim, who is in the combined B.S./M.S. program in molecular, cellular and developmental biology. The other team members — in addition to Thakral (molecular biochemistry and biophysics) — are Chidi Akusobi ’12 (ecology and evolutionary biology), Alexander Li ’12 (biochemistry), Kara Brower ’13 (biomedical engineering/chemistry), Steven Zhu ’14 (economics/molecular biology), and Darren Zhu ’14 (chemistry/mathematical economics), who is on a leave of absence this year to pursue a startup venture in robotics in Silicon Valley after winning a Thiel Fellowship.

“We started brainstorming in weekly meetings and looked at 10 to 15 potential projects,” recalls Zhu. “Then we met in smaller groups to investigate each project. The hardest part of the process was going from having these big ideas we were excited about to reaching a balance between ambition and practicality as we narrowed our focus to just one project.”

All of the iGEM teams are given a kit of biological parts from the Registry of Standard Biological Parts, a collection of genetic parts used in synthetic biology. They are then required to design and construct a simple biological system from these parts and operate them in living cells. Teams also submit their own genetic parts, called BioBricks.

At the regional competition held earlier in Indianapolis, the Yale team was awarded a gold medal and the coveted prize of Best Natural BioBrick for its antifreeze protein.

“It’s an amazing accomplishment for a team as new as Yale’s to win, in my opinion, the most prestigious of the special awards,” says Dan Spackowicz, one of four graduate students who served as mentors to the student team. “The way each team supplies a biological part makes the student members global scientists.”

Sharing and support. As the team was perfecting its antifreeze protein, Hakim received requests for his team’s BioBrick from the Stanford University team and from a group in the Netherlands for use in their iGEM projects. This kind of collaboration with iGEM competitors is common, says Hakim.

“With our research and our project, we’re not just sucking resources but are giving something back to the community,” he explains.

Hakim says hhis many hours of research for the project taught him that “science never ends.”

“Sometimes the cells are not on your schedule,” he comments. “Darren and I had many late nights during the summer where we were unable to leave the lab because of where we were in the process.”

In addition to Spakowicz and graduate students Jen Nguyen, Adam Trexler and Rebecca Brown, the team also received support from lecturer Kaury Kucera, who helped launch the first Yale iGEM team last year and encouraged the support of the Sackler Institute. Advice, ideas, lab space and support also came from Yale faculty members and research scientists Farren Isaacs (who gave overall project direction), Nigel Grindley, Lynne Regan, Cathy Joyce and Tim Craggs, and from scientists in the labs of Scott Strobel, Thomas Steitz, Yorgo Modis, Dr. Erol Fikrig and Richard Baxter. Noble, who earned her Ph.D. in molecular biophysics and biochemistry at Yale in 2009, also assisted the team with scientific and logistical concerns.

“The beauty of our project is that ieven with the support and advice we’ve gotten from faculty and graduate students, it is completely student-run,” says Kara Brower ’13. “As undergraduates, to be able to work on something that you can truly say is your own is really rare. Individually, each of us contributed with something we specialized in, from counting cell plates to designing our website. The help we’ve gotten from graduate students and faculty, I think, just shows the strength of science on campus and the support for undergraduates.”

Adds Zhu, “We’ve really gotten a full, immersive lab experience.”

Shortly before completing the finishing touches for its project, the team is feeling confident about the iGEM competition.

“We are excited,” says Hakim, “and I think we are pretty prepared.”

Graduate student Nguyen, who helped the team with crystallography, says that whatever the outcome of the competition, the Yale team has already proven its scientific ingenuity.

“This group is awesome,” she says. “Everyone on the team should be really proud of what they’ve done.”

YaleNews will announce the results of the competition. The Yale iGEM team will give a presentation about its iGEM project on Thursday, Jan. 12 at 4 p.m. in Rm. 107 Mason Lab, 9 Hillhouse Ave.

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Susan Gonzalez: susan.gonzalez@yale.edu,