Modern alchemy

Above: Student conducting research in the iGEM lab (Photo by Carolyn Lagatutta).

The International Genetic Engineering Machine (iGEM) program at UC Santa Cruz’s Baskin School of Engineering has won gold four years in a row at the iGEM Grand Jamboree in Paris. But a decade of iGEM alumni agree that winning so many top honors is not even the best thing about their experience. Shining most brightly is their transformation within.

IGEM—an annual competition of more than 350 university teams from around the world—aims to educate the next generation of scientists about responsible use of synthetic biology. But it ends up doing much more. 

“Our project, PoPPY (Portable Progesterone Production in Yeast), really started when we saw that a group of women in Africa had posted GoFundMe pages trying to raise money to pay for condoms or other birth control,” said iGEM alumna Jess Scherer (Rachel Carson ’19, bioengineering). “It sparked this life-changing aspect of our project. We reached out to the women, and as we read some of their responses, we were brought to tears.”

In fall 2017, Scherer and her fellow iGEM teammates were trying to choose a novel bioengineering project aimed at improving quality of life in underresourced areas. The team had already brainstormed a wide range of ideas, including bioengineering anti-venom for snakebites. But when they learned that many women in Africa face difficulty, stigma, and even danger when trying to obtain contraceptives, the choice was clear. 

The team talked with their iGEM mentor, Associate Teaching Professor David Bernick (Ph.D. ’10, bioinformatics and biomolecular engineering), and soon they were busy in a UCSC lab figuring out how to use synthetic biology in a way that no one had before. For five quarters, the team of 15 undergraduates—mostly juniors—worked long hours together to bioengineer a progesterone-producing yeast strain that could grow on dairy, to create a sustainable and affordable “grow-at-home” contraceptive for women anywhere in the world.

Today, Scherer—now a T-cell therapy researcher at Caribou Biosciences—says that UCSC’s iGEM program changed her life. 

“It was such a special experience,” she reflected. “I think a lot of what I do now with my cancer research is really impacted by the experiences I had in iGEM, like understanding and appreciating the human aspect of research. It truly changed the pathway of my life, and I know a lot of our teammates were very moved by the experience.” 

IGEM started small at the Massachusetts Institute of Technology in 2004 and came to UCSC in 2013, when graduate student Jeff Nivala (Ph.D. ’14, chemistry and biochemistry) and a small team launched the first iGEM summer program at UCSC, similar to Nivala’s iGEM experience at the University of Washington. The next year, two new team captains—Rolando Cruz Perez (Kresge ’15, biomolecular engineering) and Renee Jocic (Crown ’15, biology)—took the lead and soon had their team assembled in a Baskin group study area.

“I remember our newly formed team sitting in front of all these whiteboards, brainstorming about what the project could be,” said Perez, who now divides his time between Blue Marble Space Institute of Science at NASA Ames and Stanford University. “We had biofuels on one whiteboard and other ideas like microbial batteries and bioelectronics on others. It was great being there with this new team, brainstorming so many possibilities.”

 

Mentoring

The iGEM team needed an adviser. Since they’d chosen a biofuels-focused project, they approached David Bernick, who was working to introduce a biofuels program at UCSC. Bernick agreed and found the experience so rewarding that he decided to mentor again in 2015. He’s been doing it ever since.

UCSC iGEM had no funding at the outset, and Bernick had no research funds to apply. 

“We were borrowing literally everything,” Bernick said, “from chemistry to glassware.” 

Through sheer force of will and hard work, the team pulled together and raised enough money to buy needed supplies and send all but one team member to the annual iGEM Jamboree in Boston. (Co-captain Perez declined to go, due to the team’s financial constraints and his other labwork obligations.) This team effort kicked off an annual iGEM tradition: an all-team fundraising rush to cover expenses and ensure that every team member can attend the Grand Jamboree—now held at the Paris Expo Porte de Versailles, where some 2024 Summer Olympics events will unfold.

 

Meaningful projects, self-discovery

At UCSC, iGEM projects are student-led and socially significant, giving undergraduates a rare opportunity to choose their own meaningful projects, make their own research decisions, experiment with novel ideas and concepts, and have the satisfaction of knowing that the results of their hard work and discovery are truly their own. This approach empowers students to discover as much about themselves as they do about synthetic biology. And in that space, greatness blossoms.

Over the last four years, UCSC has won gold medals at the iGEM Grand Jamboree for:

• TABI (Toxic Algal Bloom Interference), seeking a solution to dangerous microcystin levels in local freshwater sources; 
• Helo, increasing access to affordable Type 2 diabetes treatment; 
• Progenie, disarming pathogenic E. coli bacteria without the need for antibiotics; and 
• Komaplastics, a biodegradable thermoplastic derived from bacterial cellulose to reduce microplastics damaging the environment. 

Prior teams have tackled novel research toward protecting live Newcastle Disease vaccines, creating accessible contraceptives, decentralizing production of medical and dietary supplements, reducing agricultural waste, and engineering microorganisms to improve biofuel production.

Whether the result of any given project is ultimately successful, the research remains valuable and available for scientists to build on in the future. The same goes for the learning and transformation that takes place within iGEM students.

“I learned to love failure in science,” said David Kelaita (Porter ’22, biomolecular engineering), who is now earning his Ph.D. in biological engineering at CU Boulder and hopes to teach someday. “We’d run into problems and have to troubleshoot, but over the course of iGEM I realized those situations are really what teach you about science.”

 

Trying and failing—and learning

Through UCSC’s unique approach to iGEM, students gain valuable confidence to try, fail, and try again, learning to view potential sidesteps as learning opportunities rather than mistakes to be feared or covered up. In the process, they make meaningful and life-changing discoveries on two exciting frontiers: synthetic biology and their own potential.

As a mentor, David Bernick draws from Aristotle’s theory of experiential learning. 

“If you want to learn to build a house, get yourself a hammer and start pounding nails,” Bernick said. “It’s that fundamental. If you want students to know the joy and heartache and absolute thrill of discovering something that literally no one else in the world knows, give them a research problem that’s nuts. Ask big. That’s the adventure we set out on. Every year, I’m shocked at the joy and sincere desire that students bring when they start the program and the confidence they walk out the door with as competent scientists.”

During the Helo team’s research, for example, students found an obscure reference to the DNA sequence of a small peptide in Gila monster saliva, which ended up forming the basis of their experiments to create an orally deliverable Type 2 diabetes medicine. 

“We came across the research in a random paper from back in the 1980s and were able to use that DNA sequence in synthetic biology,” said Gia Balius (Rachel Carson ’24, molecular, cell and developmental biology), who is working in the Bernick Lab during her last quarter at UCSC. She plans to take a gap year and apply to Ph.D. programs in biomolecular engineering. 

 

Seeds of startups

So what happens with all the iGEM projects and research after the Jamboree? Findings are published, research is labeled and stored, and future iGEM teams sometimes decide to build on past work for current projects. But does it end there?

“Many of these iGEM ideas are much closer to being startup ideas than people realize,” said Pavle Jeremic (Oakes ’17, biomolecular engineering), who founded his company Aether with some iGEM teammates after graduation. “I think more people should try to take their iGEM projects beyond the end of iGEM. If you think your idea has legs, there’s no reason why the project should stop when the Jamboree’s over. The hardest thing about a startup is not usually the technology, it’s finding a market. So if you have an idea, even if it’s not working yet but you’re seeing a lot of excitement and interest, I think that’s a very good indication to take the extra time and get it to work.” 

Undergraduates, and even high school students, are much more capable of doing advanced research and engineering than people think, he added. 

“Oftentimes when kids do research, that research is almost menial labor, like, ‘Just process these samples over and over again,’” Jeremic said. “I think it’s a disservice to those kids. One of the most valuable things about iGEM is that it’s an engineering program end-to-end, and you’re trying to build an end-to-end product or technology.”

 

Gratitude for ‘lab dad’

Over the years, project ideas change, students come and go, and UCSC sends a new team each year to the iGEM Jamboree. But the spirit of iGEM remains constant at UCSC, and alumni invariably attribute this to David Bernick and his mentorship over the years. 

“We used to call him our lab dad, and I think that sums it up pretty well—he’s the perfect balance of sound advice, kindness, and sternness,” said Claire Bispo (Merrill ’19, biomolecular engineering), who seemed to speak for countless iGEM alumni over the last 10 years. “When I doubt myself, I remember how much confidence he had in us. And I would say to him, ‘Thank you. Thank you for always believing in us.’”