Powering Synthetic Biology Projects with iGEM

Lily Helfrich

A Partnership to Power Innovation

In support of our goals to accelerate innovative research and to empower scientists, Benchling partnered with the iGEM Foundation for their 2019 season. The iGEM Foundation is an independent, non-profit organization that is committed to advancing synthetic biology through education, competition, collaboration, and community. iGEM teams — the majority of which are made up of undergraduates — use synthetic biology to address critical problems. Each year, in a celebration of new ideas and collaboration, iGEM teams representing academic institutions around the world meet to showcase their innovative synthetic biology projects at the iGEM Giant Jamboree. Leading up to the event, which took place in Boston this November, we had the opportunity to talk with five teams across the United States, the United Kingdom, and China about their projects and motivations. Like many others we met at the Jamboree, these teams used Benchling to design sequences and manage their data as they tackled problems from climate change to disease. Read on to learn a little more about each of their creative projects.

Oxford iGEM: Developing a "Super Probiotic" to Target Clostridium difficileInfection


Track: Therapeutics• Wiki: Oxford iGEM — ProQuorumNominee for Best Undergraduate Therapeutics Project, Gold Medal

The 9-person undergraduate iGEM team from University of Oxford took on Clostridium difficile infection, one of the most prevalent hospital-acquired infections in the developed world. The team's synthetic biology project focused on engineering a "super probiotic" that could target Clostridium difficile during an infection, which predominantly affects patients over 65 and often arises after a course of antibiotics. Their super probiotic, called ProQuorum, would be a dynamic Lactobacillus reuteri chassis that could both detect and selectively kill Clostridium difficile in the human gut. With some creative biological engineering, Lactobacillus reuteri would detect a quorum signaling molecule produced by Clostridium difficile and would respond by inducing the expression of a phage-derived endolysin. The team suspected that this endolysin could specifically target and cause lysis of Clostridium difficile, while leaving other gut bacterial species untouched. Over the 2019 competition season, the team ultimately demonstrated a proof of concept. In recognition of their work, they were nominated for the Best Undergraduate Therapeutics Project at the Giant Jamboree.

"With Benchling, we learned that we can easily collaborate, and we can have all of our protocols in the same spot. Because everything's on the cloud, we don't have to be constantly sharing files amongst ourselves. And that's really the reason why we kept using Benchling — because we can have everything constantly updated in real-time." - David Schramm, Oxford iGEM

Rice iGEM: Engineering Climate Resilience into Plants with Temperature-Sensitive Bacteria


Track: Environment• Wiki: Rice iGEM — ThermoplantGold Medal

The undergraduate team at Rice University has a 7-year legacy of successful, creative iGEM projects. This year, the team took on iGEM's Environment Track. Recognizing that climate change has contributed to decreasing agricultural yields over the past three decades — a trend expected to continue – the iGEM team applied synthetic biology to the problem and designed a project that they called Thermoplant. Their goal was to develop a strategy that could ultimately be used to make plants more resistant to heat and drought. Rather than engineer plants themselves, Rice iGEM team members wanted to engineer a species of rhizobacteria, or soil bacteria that form symbiotic relationships with plants. In their design, Pseudomonas putida, a rhizobacteria, would confer stress resistance to Arabidopsis by producing three enzymes that have been shown to help mitigate the plant's stress response. But the rhizobacteria would need to only produce these enzymes at a particular temperature. To account for this, the Rice team turned to RNA thermometers: they would engineer an RNA thermometer that, at 30°C, would initiate translation of a transcription factor. Upon its translation, this transcription factor would induce the expression of their three enzymes. The vast majority of their lab work went into the development of their RNA thermometer designs — and several new parts for iGEM's Registry of Standard Biological Parts, some of which they named "RNA Thermometer NoChill."

"I like the Benchling Notebook a lot. I'm not a big fan of paper notebooks. If you want to put in a picture, you have to actually print our your picture and paste it in. And I like being able to create tables without taking out a ruler. On paper, it also takes more time to read people's handwriting!" - Claire Young, Rice iGEM

"We use a lot of borrowed part plasmids from one of our graduate advisors. All of his plasmids are in his lab group's Benchling organization. So we can find his folder of part plasmids and and copy them over to ours. That way, we can find and use relevant sequences quickly." - Alicia Selvera, Rice iGEM

CU Boulder iGEM: A Vision for Safer, Small Molecule-Responsive Monoclonal Antibodies


Track: Therapeutics• Wiki: CU Boulder iGEM

At the University of Colorado Boulder, the 2019 undergraduate iGEM team built upon a project that was initiated by the previous year's team: designing a small molecule antibody switch. Both teams were interested in monoclonal antibody (MAb) therapies. While current monoclonal antibody therapies have demonstrated efficacy in treating cancers and autoimmune disorders, they have also been linked to immunotoxic effects, including exaggerated immune responses. The 6 members of this year's CU Boulder iGEM sought to address monoclonal antibody therapy immunotoxicity by creating an antibody with a "kill switch." They designed and modeled an antibody with an additional domain — AraC, a bacterial transcription factor — that dramatically changed its conformation upon binding to a small molecule — arabinose. In this design, the arabinose would act as an inhibitor, inducing a conformational change that should render the antibody nonfunctional. Over the competition season, CU Boulder iGEM designed their parts and extensively modeled the antibody switch, which next year's team may have the opportunity to produce.

"I'm a very visual learner, so I love being able to annotate and visualize plasmids in Benchling."

- Manasa Ponnapalli, CU Boulder iGEM

"We also use the Notebook; it's really easy to follow protocols and add a day-by-day list of what we're doing."

- Lauren Vanhousen, CU Boulder iGEM

Edinburgh iGEM: A Device and An Engineered Microbe for the Efficient Production of Biohydrogen


Track: Environment• Wiki: Edinburgh Undergraduate iGEM — HydrolyteGold Medal

Every year since 2006, students at the University of Edinburgh have participated in the iGEM competition. This year's team surprised some of their advisors when they told them they'd be producing and collecting hydrogen in the lab. They had come up with an idea to design a device they called "Hydrolyte," a chamber in which they'd optimize the production of biohydrogen by engineered microbes. Inspired by the United Kingdom's goal to reduce their emissions to net zero by 2050 and by the issue of fuel poverty in parts of the UK, Edinburgh iGEM wanted to use synthetic biology to produce clean energy. They became interested in hydrogen: using bacteria to produce hydrogen could be renewable, but current methods were expensive and inefficient. As the team designed Hydrolyte, they hoped to solve for cost and resource efficiency. They prototyped a device with a hydrogel containing Rhodobacter sphaeroides, a bacterium that efficiently produces hydrogen during photofermentation. They simultaneously worked to engineer different hydrogenases into R. sphaeroides, hoping to increase its natural rate of hydrogen production. Throughout the competition season, the team also invested time in learning more about fuel poverty in Scotland, particularly in rural communities, and about what it would mean to design a practical, meaningful solution to this problem.

"With Benchling, you can show what you're working on directly to your supervisors."

- Maria Fernandez, Edinburgh iGEM

"Rather than write an email explaining something that [our supervisor] can't visualize, it's easier to just say 'Come over, we'll just show you the design on the computer.'"

- Annabel Wright, Edinburgh iGEM

NEFU China iGEM: Scaffolded DNA Origami and Bacterium-Based Cancer Treatment


Track: Therapeutics• Wiki: NEFU China iGEMGold Medal

The iGEM team at Northeast Forestry University (NEFU) in China was one of the largest, with 25 undergraduate team members and nine advisors. Given their diverse interests, the team started out the season with multiple projects. One of those focused on developing a technology that could be used to efficiently drive multi-substrate enzymatic reactions. They envisioned what they called "scaffolded DNA origami," a technique in which they'd anchor the enzymes involved in subsequent steps of a reaction by linking the enzymes to zinc finger proteins and engineering those zinc finger proteins to bind a DNA sequence in an ordered fashion. Meanwhile, other members of the team explored a completely unique but equally creative project: a therapeutics project that focused on treating cancer using an engineered bacteria – E. coli. NEFU China iGEM team members set out to engineer a strain of E. coli to selectively kill tumor cells without releasing too much uric acid (a buildup of uric acid is a complication associated with conventional cancer treatments). Their engineered E. coli would sense a hypoxic, acidic tumor microenvironment and would respond by releasing a mutant form of tumor necrosis factor-α (TNF-α) that can act as a targeted anticancer agent. As the season progressed, NEFU China iGEM converged upon their E. coli-based cancer treatment project and presented it at the Giant Jamboree.

"In our regular meetings, we always use a live website such as Benchling to share our data. With Benchling, we upload our own data, and we see what others have uploaded. It has helped us a lot!"

- Chuyue Zhao, NEFU China iGEM

Benchling's Reflection on iGEM 2019

Like most iGEM teams, each of these teams was interdisciplinary, representing undergraduates across biology, biochemistry, chemistry, and engineering. Working collaboratively, they developed creative ways to apply synthetic biology to a meaningful, practical problem. Both through our iGEM partnership and our software, Benchling is proud to support these and other iGEM teams as they pave the way for the future of biological innovation.

If you want to learn more about how iGEM teams used Benchling, check out this story on the iGEM blog.

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