By Melissa Weckerl

Originally posted on UC Santa Cruz NEWSCENTER

This year’s team of student innovators, members of the UCSC International Genetically Engineering Machine (iGEM) program, is addressing a local yet widespread environmental issue: harmful algal blooms in Watsonville’s Pinto Lake.

The team’s bioengineering approach targets the toxic genes of the specific bacteria responsible for the algal blooms, creating a non-invasive, long-term solution to preserve biodiversity, ecosystem balance, and public health.

Driven by the high levels of phosphates found in agricultural run-off, Pinto Lake has been experiencing toxic algal blooms for the past four decades. But these blooms, which are specifically caused by a type of freshwater cyanobacteria called microcystis aeruginosa and found in many bodies of water across the globe, have become more toxic and pervasive over the past decade as we experience warming temperatures due to global climate change.

Exposure to microcystis via ingestion or contact with contaminated water is extremely harmful to humans and animals, causing severe sickness that could lead to liver failure and death.

“With Pinto Lake no longer receiving funding from the state to address the toxic algal blooms, there is a clear need for a solution that is not prohibitively expensive and will continue to work in the long-term,” said Varun Kodur, co-captain and fourth-year molecular biology student. “We are the first group of researchers to take an active intervention to Pinto Lake’s toxicity using synthetic biology.”

A long-term, scalable solution

Team UCSC’s synthetic biology approach involves designing and assembling a plasmid—a small DNA molecule found in bacteria—that targets and inactivates the toxic-causing genes in the cyanobacteria instead of killing it. This provides a tangible and scalable long-term solution with minimal disruption to the lake’s ecosystem.

The team, consisting of 14 undergraduate student researchers and three interns advised by Associate Teaching Professor David Bernick, is drawing from the field of bioinformatics to validate their proof of concept.

Building off of STEALTH, a software program developed by Professor Bernick, the team has created a tool called Chameleon that will improve transformability of non-model species like microcystis. The tool tailors plasmids to the genetic signature of any organism by removing short sequences that are genomically underrepresented, without altering the functionality of the plasmid. They will apply Chameleon to disrupt toxin production in microcystis, allowing this type of cyanobacteria to continue its ecological niche and produce offspring without toxic genes.

In addition to the software pipeline they have built, the team is developing a suite of open source software tools and will be releasing the genomic sequence of the specific microcystis strain they are working with, a complex endeavor enabled by nanopore sequencing technology, a revolutionary method for sequencing long reads of DNA and RNA.

“We really wanted to contribute to the bioengineering community, so the bioinformatic approach was clearly the greatest area of impact our team could have in the short amount of time we have,” said Jordan Nichols, co-captain and fifth-year biomolecular engineering student.

Community engagement, partnerships, and countdown to competition

The team’s inspiration for their project came after talking with UCSC Ocean Sciences Professor Raphael M. Kudela, who has been closely tracking the algal blooms in Pinto Lake for some time. Once they finalized their project plan, they immediately got to work building connections with the local community, including frequently communicating with the Pinto Lake manager and with the extended UCSC environmental research community. Their research outreach has led to new insights and guidance in improving their experimental design and genomic sequencing protocols.

In addition to the months of brainstorming, research, and wet lab work, a longstanding and important aspect of the iGEM program is community engagement. This year’s team has been engaging with their local community in several ways. They have given talks at local high schools and programs and invited students from Watsonville High to get involved with the work they are doing on site at Pinto Lake.

“We’re very much leaning into the education aspect of outreach and getting people who are younger than us inspired to do something like this, using synthetic biology to help their community,” said Blanca Davila Gil, iGEM team member and biomolecular engineering fourth-year student.

In addition to their local outreach, the researchers have furthered their engagement impact by partnering with UC Berkeley to help restart their iGEM program. As a program that has been around for almost 10 years at UCSC, the team feels immensely gratified to be able to provide the Berkeley community with the resources and guidance needed to successfully carry out a complex, student-led synthetic biology project.

Co-captains Kodur and Nichols and team member Davila Gil attribute the team’s success so far to being self-starters, motivated to make an impact in the environmental engineering space.

“We have a good balance going on with people doing the stuff they have experience in to get project tasks completed but also having the opportunity to work in areas they don’t have experience in to gain new skills and further their interests,” Kodur said.

The annual international synthetic biology competition, known as the iGEM Jamboree, will be held November 2–5 in Paris, France. With just one month left until the competition, the UCSC iGEM team is completing several wet-lab and software-related tasks, including successfully assembling their plasmids, validating transformation in microcystis, and validating that their software pipeline improves transformation efficiency.

They are looking forward to creating a detailed video to present their project and engaging in a Q&A with a panel of judges at the competition. They hope to bring home another gold medal, following consecutive gold medals awarded to the past three iGEM teams: Helo (2022), Progenie (2021), and Komaplastics (2020).

“Everyone’s heart is in the right place. We’re here to learn and contribute what we can,” Nichols said. “Our yearning for wanting to be bioengineers and make a positive impact is apparent in all that we do.”