We Are USCience

Undergrad biologists and engineers unite to form USC’s first-ever team in the premier international synthetic biology competition, iGEM, under the USC Davis School of Gerontology’s Sean Curran, Ph.D.
By Jonathan Riggs

(l to r) Kevin Le, Nolan Sardesai, Sean Curran, Ph.D., Percy Genyk, Dongzhu Wu, Ellen Park

The USC students’ goal was simple, really: utilize the techniques of synthetic biology and genetic engineering to design bacteria to perform unusual and uncharacteristic actions.

But what actions should they make their creations perform? Play checkers? Respond to music? Produce electricity?

Instead, they decided to take the easy way out: manipulating the genes of the recently discovered “immune” system of bacteria to make them susceptible to antibiotics, which could help contribute to the global fight to eradicate the terrifying and deadly phenomenon of drug-resistant superbugs.

You know: child’s play.

Running the gamut from freshmen to seniors and uniting biologists and engineers, the six-student team consisted of USC students Alexa Hudnut, Dongzhu Wu, Ellen Park, Indira Bhavsar, Kevin Le and Percy Genyk. By pooling their unique perspectives and disciplines, the team competed in The International Genetically Engineered Machine competition (iGEM)—the planet’s premiere undergrad synthetic biology competition.

“USC is a world-class research institution, but up until now had not established an iGEM team. When I was approached by Nolan Sardesai about the possibility, I jumped at the opportunity,” said the team’s faculty advisor Sean Curran, Ph.D., of the USC Davis School of Gerontology. “This is a fantastic program and opportunity to show undergraduates how exciting, rewarding and fun bench science can be.” 

The team’s student advisor, Sardesai, earned his bachelor’s this year from the USC Viterbi School of Engineering, where he is currently a grad student. He has always been enthralled by science, ever since his days as a tyke watching The Magic School Bus or Bill Nye the Science Guy.

“Science is just so fascinating and completely boundless—the possibilities to what can be discovered and explained, the ‘whats’ and ‘hows’ to life—are limitless,” he said. “Though there have been some hardships in forming this team and garnering support, USC—especially the Davis School of Gerontology, the Viterbi School of Engineering and the Dornsife College of Letters, Arts, and Sciences—have given us and future USC students the opportunity to support and enhance ongoing research in one of the next big scientific fields: synthetic biology.”  

Recognizing that the public may have ethical and safety concerns about bioengineering, the team used social media to start a dialogue and to clear up any misconceptions.

“Educating the community with facts on these issues will not only create a well-informed public, but will push us as a society to think about the next generation of questions and potential applications of synthetic biology,” Curran said. “We hope to utilize the expertise of the faculty and students in the Schools of communication, public policy, education, film and television and others to achieve these goals in the future.”

WEIRD SCIENCE

To compete, each team around the world is given a kit of biological parts at the beginning of the summer, which they must use alongside new parts of their own design to build biological systems and operate them in living cells. Thanks to the USC team’s creativity and variety of scientific disciplines and research perspectives, they were able to consider many possibilities before settling on the one they agreed would most help further the joint causes of science and humanity: dismantling the resistance of superbugs to antibiotics.

Titled “E. Curi,” the project focused on the infamous E. coli bacterium, drawing upon bacteria’s recently discovered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system as well as CRISPR-associated (CAS) genes.

“Superbugs carry genes that make them immune to the drugs normally prescribed to combat infections. So our team asked the question, ‘how can we get rid of those antibiotic resistance genes?’” Curran said. “It turns out that the bacteria keeps these genes on circular pieces of DNA called plasmids. In modern molecular biology, we use plasmids every day to engineer bacteria to do what we need them to do.”

Although getting DNA into bacteria is a universal lab practice, the team faced the unique challenge of getting it back out — in effect, manipulating the bacteria to destroy its own plasmid DNA on command.

“Fittingly for USC, we modeled our system after the Trojan Horse to trick the bacterium into taking up our system,” Curran said. “Once activated, it can target and destroy any plasmid that we program the system to recognize. In medicine, this could be used to eliminate antibiotic-resistance plasmids. In the lab, this is a way to turn any biological system off.” 

“We essentially manipulated the CRISPR/CAS system to target and remove an antibiotic-resistance gene that we implanted into the bacteria, thus making them once again susceptible to antibiotics,” Sardesai said. “Our hope is that our work can eventually contribute to the ongoing battle of increased bacterial resistance to modern antibiotics by removing the resistance altogether.”

TEAMWORK

Achieving their desired breakthrough with the project and the prospect of its far-reaching potential electrified the team members, who saw their determination and enthusiasm rewarded.

“What is awesome about our project is that it works!” said Genyk. “I learned that research is 90% frustration and 10% success. The success part is like a shot of adrenaline that makes you look past the frustration. This was a tremendous opportunity and privilege to work like Ph.D. candidates.”

“Before iGEM, I had no idea how much planning and practice research entailed. After working in Dr. Curran’s lab, though, I found that the rewards outweigh the costs,” Park said. “Even better, our results have a really promising future, so knowing that I contributed to something of so much value is more than I could ever ask for.”

“Before getting our results, we faced many failures, but with a lot of repetition and rethinking, we made our system work,” Wu said. “I didn’t have a lot of research experience in biology, but after a short training, I picked up a lot of skills. Now, I am even thinking about pursuing my future degree in the area of biology.”

“We all came from different majors, different backgrounds and have different goals in life. Nonetheless, we all worked incredibly well together. Even during the longer days in lab, everybody was willing to help each other out,” said Le. “I am an inexperienced researcher, and have never worked in a lab before, but I could always count on the other researchers to be patient and teach me what I needed to know.”

The students weren’t the only ones who came away from the experience with a valuable new insight and appreciation for the future of the field, however.

“iGEM is all about creative thinking. The fact that the group had very little practical lab experience before iGEM is a testament to their hard work, dedication, and their eagerness to learn,” said Curran. “I am incredibly proud of all they have accomplished.”

“Since this past February, the team members have attended countless meetings and research sessions, spent hours in the lab and in front of computers and books, and their work undoubtedly paid off,” said Sardesai. “The success of iGEM at USC is entirely due to them, as well as Dr. Curran. In three words: Best Team Ever.”  

THE SCIENCE OF SUCCESS

Although the team did not win the competition, they came away from the experience with a deepened appreciation for their chosen field, as well as a victory much more lasting and life-changing.

“I learned that I enjoy doing research because I am working to make advances,” Wu said. “If I gain a wide range of knowledge about science, I may be one of the people who can change our daily lives.” 

“Despite some struggles and setbacks, our team stuck with it and helped each other overcome barriers. I can’t say enough how much I appreciate every single member,” Park said. “I’d also like to make a shout-out to Dr. Curran. He’s not only one of the kindest and most genuine people I know, but he’s one of the biggest reasons the team had so much fun over the summer.”

“I learned from my experience in this lab that above all else, hard work is what brings you to the top,” said Le. “By watching Sean, the members of his lab, and the rest of the USC iGEM team the past few months, I’ve learned that it takes enormous amounts of dedication and confidence in your work to accomplish something phenomenal.”

Seeing their six students stretch across disciplinary lines to crystallize into a supportive, dynamic team, devoted not only to science but also to each other, makes their advisors just as proud as if the team had taken first place.

“Future teams will have big shoes to fill because of the great talent and dedication we were able to find,” said Sardesai. “The things that our team and other researchers at USC are doing are amazingly groundbreaking, and I am very proud to be a part of it all.”

“I was thrilled to learn how passionate the students were to work in the lab and how self-motivated they were to rise to any challenge. That’s a clear sign that the University is achieving its goal of educating and fostering the next generation of great thinkers,” Curran said. “The practical applications of synthetic biology are only bounded by the limits of our imagination, and with students of such potential, I can’t wait to see where the future takes us.”

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