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U.Va. iGEM team aims to revolutionize biosynthesis in a metabolic engineering project

Undergraduate competitors win silver in worldwide synthetic biology competition

<p>In November, the University’s 2021 iGEM team competed in the annual, worldwide iGEM Competition with their metabolic engineering project "Manifold."</p>

In November, the University’s 2021 iGEM team competed in the annual, worldwide iGEM Competition with their metabolic engineering project "Manifold."

The University’s iiGEM team is working on a project entitled “Manifold” to build a platform technology that makes the process of metabolic engineering more efficient and would revolutionize biosynthesis. 

The International Genetically Engineered Machine Foundation hosts an annual worldwide iGEM Competition during which teams design and construct new biological systems and operate them in living cells. The University team competes in this program against 253 other collegiate teams coming from all over the globe, with more than 40 countries participating. Last year, iGEM hosted the competition online.

This past November, 11 members of the University’s iGEM team won a silver medal in the iGEM Competition, an international synthetic biology event . 

The overall purpose of iGEM is to facilitate the future of biosynthesis and related technologies by allowing high school students and undergraduates to pursue their budding passion for research.

Third-year College student Joel Valliath said iGEM was a unique experience, since most students never get the chance to work independently with their peers to brainstorm and develop a project. 

“The idea of our project is creating bacterial microcompartments inside of bacteria,” Valliath said. “These are essentially protein shells that we’re creating inside bacteria, and they’re laid on the interior with these things called DNA scaffolds. The purpose of it is to streamline any sort of biochemical process to make it much more efficient.”

Bacterial microcompartments are organelle structures containing enzymes and other proteins contributing to the metabolic versatility of bacteria. The DNA scaffold controls the number and type of enzymes in the metabolic pathway. For instance, one enzyme might work a little bit faster than another enzyme, therefore enabling metabolic flux control. Metabolic flux is the rate of turnover of molecules through a pathway, which is regulated by the enzymes involved. 

Under the guidance of Assoc. Biology Prof. Keith Kozminski, members of the team must first enroll in a semester-long synthetic biology course that provides the competitors with a foundation for the engineering design cycle, making recombinant plasmids — which are plasmid vectors with inserted DNA that drive recombinant DNA into a host cell — and learning basic synthetic biology techniques.

Learning and practicing synthetic biology techniques such as reading the DNA code, copying existing DNA strands and inserting specific DNA sequences into existing strands are principal facets of the project preparation.

The engineering design cycle is necessary for projects because it ensures aspects such as objectives, constraints and evaluative testing are met. 

“I didn’t really have research experience and this was dipping my feet into it,” Valliath said. “I thought iGEM was a really great way to get started.”

iGEM has two divisions, high school and collegiate, where student teams compete against each other in their respective divisions. Valliath explains how iGEM is a program open to students from any background and with any interest in scientific research.

“iGEM as a whole is more about inclusion and not being exclusive,” Valliath said. “One of the foundational aspects of iGEM as an international organization is trying to get people from underrepresented communities involved in research.”

Marketing the program to everyone at the University and not simply students with prior research experience is a crucial part of the application process. 

Collin Marino, third-year Engineering student has been an iGEM competitor for two consecutive years and is the team captain of the University’s iGEM team. Marino wrote this year’s project proposal, with the goal of making the metabolic engineering process easier to scale up to an industrial level. 

“I designed a lot of the actual DNA and parts that we had to assemble,” Marino said. 

Marino’s first year on the iGEM team was affected by the COVID-19 pandemic, which resulted in a change in the team’s project timeline. The initial project idea was proposed by Marino the previous year, but due to the constraints of the pandemic, it became a two-year long process compared to the one-year long project normally completed by iGEM competitors.

“We had this interesting situation where we did a continuation of our project,” Marino said. “In the first year, we didn’t get to do any real lab work and just planned, and the second year we actually got in the lab and started working.”

Marino emphasized how his position as captain required him to account for all the intricacies that go into a team effort. Assessing people’s abilities, personalities, motivation and, most importantly, happiness are huge areas to consider, especially in a leadership position.

“Learning about team dynamics and working with a team of people is extremely useful,” Marino said. “Going forward, whether that’s working on a team of engineers or on a research team, that’s the most valuable thing and experience that I got out of this.”

Maria Lyons, second-year College student and team member, has been involved in iGEM since high school and decided to apply to the college division in the winter of her first year. 

“I’ve been doing iGEM for three years,” Lyons said. “I did it in high school with a different team, and so that was my ticket to having experience with these types of projects.”

Lyons held a management position that included assisting other members with their lab work and learning different methods of teaching. A combination of communication and biology laboratory skills are invaluable to her future career aspirations, Lyons said.

“Biology research is really interesting to me,” Lyons said. “Synthetic biology is the field of the future, and I think that it can revolutionize production efficiency in a lot of ways.”

For Lyons, the most rewarding part of working on the project was honing in on scientific techniques and expanding her research skill set. 

“We’d extract DNA and we would amplify it with PCR to look for the fragment that we put in,” Lyons said. “Every time we ran a gel [electrophoresis], we would see little stripes that corresponded to the length of DNA, meaning that we successfully put our DNA into the plasmids of bacteria. That was the best part of the whole project.”

Each competitor expressed how delving into synthetic biology impacted their research interests and career goals. Valliath enjoyed relating the medical applications of synthetic biology research with his aspirations for a career in healthcare. For Lyons, biology research holds a deeper meaning for her and is a path she is continuing to undertake. Marino expressed his ongoing passion for research as well and the future of synthetic biology.

The field of synthetic biology holds many significant advantages to address current and ongoing problems, from preserving biodiversity to developments in medical technology. Synthetic biology promotes methods to engineer crucial biological processes in order to offer specific and accessible solutions.


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