Last year the Hopkins iGEM (International Genetically Engineered Machine) team engineered yeast with the ability to produce beta-carotene. This year, they divided their efforts into two teams and took on two subprojects: one with yeast, and the second with a new cloud-based platform for plasmid design.
While both teams met the standards for gold at the American East Regional Jamboree in October, only the software team advanced to iGEM’s World Jamboree held at MIT on the first weekend of November. The software team tied with a South Korean team for Best Software Tools, and with Wellesley College’s team for Best SBOL-based tool. At the regional competition, the wetware team won an award for Best Poster.
The first of the wetware team’s goals involved developing a light control mechanism for the yeast cell cycle. According to James Chuang, a senior Biomedical Engineering major, the team was able to use blue light to bring together two proteins, which had been modified with light sensitive protein tags. These proteins play a role in controlling the cell cycle.
“The end result is that we wanted to synchronize these cells in the cell cycle by shining light, stopping them at the same point, and then letting them proceed,” Chuang said. “It’s like a traffic light for the cell cycle.”
Their second challenge addressed a problem in yeast fermentation, which, in addition for production of choice beverages, is used for the production of compounds that would otherwise be difficult to obtain from their natural sources.
“For example, the anti-malaria drug is usually found in a plant; but if you can take the pathway, just the genes, and put them in yeast then it’s a lot easier to manufacture,” Jerry Wang, a sophomore Biomedical Engineering major, said.
Yeast produce ethanol as a part of their metabolism. To take on this issue of ethanol build-up in the environment surrounding yeast cells, the team relied on a human protein whose production was controlled by the presence of ethanol.
“We introduced a human gene into the yeast cell, Cyp,” Wang said. “It’s found in the liver and responsible for breaking down ethanol, and so we designed a series of ethanol divisible promoters to be the control system.”
While the group had initially sought to use beta carotene as a test compound (drawing upon resources from their project last year), they only had enough time left to show an improvement in the health of the yeast cells with the ethanol control system in place.
For the software team, the challenge was to develop a cloud-based system to improve plasmid design. With this system, researchers can draw upon the resources of remote servers across the internet to help design the segments of DNA that they want to introduce into cells.
The cloud-based system allows a plasmid sequence to be examined against databases of important features. According to Emily Scher, a sophomore Computer Science major, this system also can detect when a part of the plasmid affects infective properties and can let researchers know when the plasmid might prove harmful.
“In [synthetic biology] these sequences are being put into cells and put into cells and used in a lab somewhere,” Scher said. “So if we had something dangerous then people would actually be hurt, it’s not like it’s just going to be sitting in a tube somewhere.”
Scher explained that with tools like the team’s Autogene, researchers working with genetic sequences can move on to a smarter means of plasmid design, involving structures rather than base pairs. This is something that she equated with the writing code instead of the binary digits 1 and 0 in computers.
“I know that in the Boeke Lab just a few years ago they were literally copy and pasting [sequences] into Word documents and rearranging them. Obviously that is not ideal,” Scher said. “A lot of people think of A’s, T’s, C’s and G’s as binary and when you code you don’t write in binary, you write in ‘for’ loops and ‘if’ statements and whatever. So we are trying to create that level of separation between binary and the structures you actually use to design.”
The software team received extensive support from Autodesk in San Francisco, where one member of the team, sophomore Biomedical Engineering and Neuroscience double major Album Shen, spent much of his summer working with the company on cloud integration. The team also benefitted from the company’s feedback as they prepared for the competition.
“It was nice meeting up with Autodesk employees and getting their feedback before regionals,” Shen said.
For the regional competition, the teams had to separately prepare 20-minute presentations and posters. For the wetware team, senior Molecular and Cellular Biology major Anna Noronha explained that while the preparation stressful, the competition was an enjoyable experience.
“It was a great way to meet other teams, see what they were doing and what their projects were, just to get exposure to what other people’s stuff were,” Noronha said.
The software team found the regional competition to be a fairly competitive scene, but Shen found their fellow competitors at the world competition to be open in their interactions.
“As far as how interactions with other teams went, regionals were pretty intense, everyone was really competitive, whereas at worlds people reached out more,” Shen said.
Both teams found the time they spent together working on iGEM projects to be an extensive learning experience. They learned a lot about tackling challenges that professionals in their field would handle.
“We’re not PhD students, a lot of us did not know what we were getting into and we learned a lot really fast,” Scher said. “It was cool and you meet a lot of people.”