Last summer, as most undergraduates spent their vacation traveling to exotic locales or lounging by the pool, one group of students spent their time on campus in an Institute for Genomic Biology lab, reading papers and creating a probiotic pill that could help prevent heart disease. "
Each day, the U. of I. iGEM – short for International Genetically Engineered Machine – team members awoke for early morning meetings, worked at the lab in shifts and then shared their new ideas on Facebook as the sun set over the Morrow Plots – before, of course, coming back to the lab the next morning to do it all again.
They were in the lab trying to create, as Ashley S. Moy, the Illinois iGEM team administrative director, said, “a genetically engineered machine: You input something in it, and it outputs something else.”
A group of dedicated Illinois undergraduates have done this synthetic biology dance in preparation for the iGEM competition since 2008. Throughout the years, they’ve always fared well, winning two bronze, three silver and two gold medals, as well as the 2010 Best Software Tool distinction.
The university’s team and its success caught the eye of Moy, a sophomore in bioengineering, when she was in high school, so when she got her chance to apply for the team last March, she did so immediately.
“I really love biology, and I was always looking online for competitions and organizations to be involved in, so I couldn’t wait to get involved here,” Moy said. “One of the other bioengineering majors posted on Facebook, ‘Hey, I’m applying for iGEM. Anyone else want to join me?’ And I thought, ‘Yes! Definitely. I will be there.’ ”
After the application and interview process, Moy and six other undergraduates (Margaret Barbaro, Blake Wilhelmsen and Rachel Walker, all sophomores in bioengeering; Xinyi “Cathy” Guo, a sophomore in molecular and cellular biology; Arnav Rana, a sophomore in molecular and cellular biology and in psychology; and Will Dolatowski, a senior in agricultural and biological engineering) were chosen for Illinois’ 2013 iGEM Wetlab team. (In biology, chemistry, genetics or biochemistry, the term “wet lab” distinguishes classical benchtop experiments handling biological material from computer analysis or other theoretical work.)
They set to work on their project the first week of June, focusing on the design of a bacterial system that could prevent cardiovascular disease.
Rana, who served as one of the team’s scientific directors, said an April 2013 study published in Nature Medicine by researchers at the Cleveland Clinic inspired their initial idea.
“What really started us out this year was a paper that found that high levels of a biomolecule called TMAO in your bloodstream leads to cardiovascular disease, or CVD,” Rana said. “What we aimed to do was destroy TMAO and therefore decrease the risk of CVD.”
Rana said naturally occurring human gut bacteria convert the compound l-carnitine, which is found primarily in red meat and dairy products, into a compound called TMA. The liver then converts TMA into TMAO, leading to the disease atherosclerosis, in which plaque buildup causes a hardening of the arteries.
Instead of focusing on the destruction of the TMAO molecule, the team decided to target l-carnitine, a precursor molecule because they knew of a bacterial species called Pseudomonas aeruginosa that already contained genes that facilitate the breakdown of l-carnitine, sending it down a less dangerous pathway; if they could destroy l-carnitine, they could keep the gut bacteria from converting this compound into the harmful TMAO.
Unfortunately, P. aeruginosa is toxic to humans. But that’s where the synthetic biology aspect of their project came into play. The group used molecular techniques to transfer the l-carnitine destruction genes into a strain of E. coli that is considered safe for humans, but didn’t originally have those genes.
“Toward the end of the summer, we had our organism completed and tested to determine how well it took up and converted l-carnitine into a less harmful substituent,” Moy said. “So we wondered, ‘How can we take this one step further? Let’s put this in a form that could theoretically be ingested by a human.’ ”
The team filled gelatin capsules with their bacteria, then sprayed the probiotic pills’ exteriors with a coating that allowed it to bypass the highly acidic stomach for eventual breakdown in the less acidic small intestine. The newly released bacteria could then compete with the naturally occurring gut bacteria for l-carnitine, thereby keeping it from breaking down into the harmful TMAO molecule.
After months of what Moy called “long days that went into long nights of failed experiments and a rapidly depleting budget,” the team finally had a finished product.
In October, they traveled to the iGEM North American Regional Jamboree at the University of Toronto to compete against 54 other teams. Their presentation went smoothly, and at the next day’s award ceremony, the team received Illinois’ third gold medal and a chance to compete in the iGEM World Championship Jamboree.
The next month, Illinois and 72 other teams traveled to the Massachusetts Institute of Technology for the international championship.
The Illinois team worked through the night, perfecting their presentation literally as they walked into the room. Everything was going as it had during the regional competition, but as Wilhelmsen began addressing the project’s safety, the computer crashed.
Despite the technical hiccup, Rana said, “He handled it amazingly.”
“People were tweeting about him afterward: ‘Congratulations, you handled that really well!’ ”
In spite of the enthusiasm on Twitter, Moy didn’t think the team would win.
“But after we walked out of the presentation room, Cathy held both my and Maggie’s hands and said, ‘Guys! We’re gonna win this!’ I still didn’t feel that confident about it,” Moy said.
The awards ceremony came the next morning. As the Illinois’ iGEM team’s name flashed on the screen for the Best Undergraduate Health and Medicine project, the team screamed and jumped with excitement.
“I remember someone almost pushing me down because I was so nervous. I didn’t think it was us, I was just making sure it was our name,” Guo said.
“It was really surprising. I didn’t expect us to win, but it made me really happy,” Rana said.
Since becoming the only U.S. undergraduate team to win an award at the 2013 iGEM World Championship Jamboree, the Illinois team has received a job offer from a U. of I. Research Park startup company as well as invitations to give talks and to enter other competitions.
As they began reading the applications for the next Illinois iGEM team, Moy reflected upon her time as its administrative director.
“Overall, the experience was absolutely incredible. The energy in the room when you’re presenting to hundreds of people is palpable. You can feel the intensity; that’s an amazing feeling.”