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Johns Hopkins Researchers Mentor Two Undergrad Teams for iGEM Worldwide Synthetic Biology Competition

Software team wins worldwide software prize; “wetware” team wins regional gold medal.

iGEM glass trophy

November, 2012-- Synthetic biology: It sounds like an oxymoron. And for sure, living organisms aren’t manmade. But sometimes single-celled organisms can be engineered to perform a “synthetic function,” something they wouldn’t normally do. By taking a gene from one organism and placing it into another organism, or by tweaking the activity of an existing gene, scientists can get these little life forms to accomplish new tasks in order to solve problems in a unique way. Algae, for example, use energy from sunlight to create oils in their cells. When those cells are pressed, the oil can be extracted and used as fuel. Scientists are using synthetic biology to optimize this process.

“Synbio” takes a lot of creativity. And what do we do when we want to stimulate creativity? Hold a competition, of course. Enter iGEM, or the International Genetically Engineered Machine competition, which has been held at the Massachusetts Institute of Technology (MIT) every year since 2004. Undergraduate students form small teams and work on research projects during the summer, then present their results in the fall at one of five Regional Jamboree competitions. The top fifth of the regional teams go on to compete in the World Championship Jamboree at MIT.

Most of the teams attempt to make a single-celled organism do something it doesn’t normally do. These teams do their experimental work on cells living in watery nutrient broths in laboratories, so they’re nicknamed “wetware” teams. For the past four years, Hopkins has entered the wetware competition and done well. Last year, for example, our team finished 16th out of 120 teams.

This year, two Blue Jay teams competed, a wetware team and a software team. Both teams won a Regional Gold Medal based on their stellar fulfillment of the competition’s criteria. Unfortunately, the wetware team was one slot away from advancing to the championship, but the software team went all the way and won the World Championship Software Prize!

“We’re really proud of both teams,” says Jef Boeke, Ph.D., professor of molecular biology and genetics at the Johns Hopkins Institute for Basic Biomedical Science and a mentor for the teams. “The competition this year was really stiff, almost 200 teams, but they held their own.”

Boeke likes the fact that undergrads have the drive to win without the fear of losing. “Even grad students have to think about how long a project will take or what the likelihood of success will be, and that can cramp their creativity a bit,” he says. “Undergrads will go for the gold and tackle challenging — even impossible — projects.”

iGEM team

The teams were supervised by postdoctoral fellows Yizhi (Patrick) Cai, Ph.D. and Leslie Mitchell, Ph.D., from Boeke’s lab at High Throughput Biology Center, and Giovanni Stracquadanio, Ph.D., from the lab of Joel Bader, Ph.D., an associate professor in the Department of Biomedical Engineering. Because of the rising popularity of the competition among Hopkins students, they had to increase the stringency of the selection process, interviewing 40 students and choosing just 12 of them, six for each team. Then the students designed their own projects.

“As a postdoc, I jumped at the chance to help with iGEM,” says Stracquadanio. “The process is really like running a small lab. It’s a great opportunity to mentor students and manage a project. The teaching experience will be valuable for my future career.”

The wetware team chose a really ambitious project: optimizing yeast for industrial applications. Yeast is most notoriously used in industry to make beer, but it has also been engineered to make cheap, effective anti-malaria drugs, for example. The hitch is that alcohol is often a byproduct of the yeast reactions, and too much alcohol slows down yeast productivity. The team’s proposed solution was to get the yeast to biochemically remove the alcohol and thus save itself. To do so, the team introduced a human protein into the yeast that converts alcohol into non-harmful molecules. The protein’s production was linked to a sensor that detected high alcohol levels.

“It’s a really neat idea that could have big applications,” says Stracquadanio.

For its project, the software team took on a database called the iGEM Registry of Standard Biological Parts. It’s a communal catalog full of all sorts of DNA sequences, each one labeled with a description of what it does and how it works. Each “piece” of DNA sequence is called a BioBrick and, just like Legos, BioBricks are made to be mixed and matched according to the vision of a young engineer. Students can order these BioBricks and add them to bacteria or yeast or even mammalian cells, where, if all goes well, the DNA will be read and made into proteins.

But as the repository grows — there are currently more than 20,000 BioBricks available — a safety risk emerges. No human being can possibly sift through everything in the catalog to make sure that it is properly labeled and safe for use. What if the mixing and matching of a few BioBricks ends up creating the sequence for a toxic compound? Or what if a typo in a sequence enables an unknown function with unknown consequences?

Seeing the risk, the Hopkins software team decided to find a solution. The team developed a new software program, dubbed AutoGene, that can recognize the messages encoded in the DNA alphabet. The program not only verifies the human notations and labels on each BioBrick, it also safeguards the researchers using the catalog by detecting disease-causing viral codes and other harmful sequences.

Normally, though, even a computer program would take an impractically long time to sort through the whole catalog and compare each entry to databases of known sequences. So the Hopkins team became the first iGEM team to use cloud computing to develop their program and speed up its processing time, “borrowing” the computing power of thousands of computers connected through the  “cloud computing” service offered by Autodesk, a high-profile software design company.

“Our software team overcame some really big technical hurdles with their hard work and creativity, and teamed up with industry in a new way,” says Boeke. “Their coveted Software Prize was well-deserved, and we are excited to see where they go from here.”

The JHU teams were supported by the Johns Hopkins University Department of Biomedical Engineering, the High Throughput Biology Center, Student Initiative Fund, Provost Undergraduate Research Award, Department of Chemical and Biomolecular Engineering, Department of Computer Sciences, Woodrow Wilson Undergraduate Research Fellowship, as well as corporate sponsors Autodesk, Integrated DNA Technologies and GenScript.

–Catherine Kolf

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