At the Alviso Marina County Park, reddish-brown water laps at the edge of a salt flat, a remnant of industry that once dominated the south Bay Area. With bobbing shorebirds as company, a group of UC Santa Cruz undergraduate students collect water samples from this dynamic but understudied environment, to bring them back to campus and identify the microorganisms within using cutting-edge DNA sequencing devices.
These students are part of the class “Foundations of Design and Experimentation in Molecular Biology, Part II” (BME 23L), a required course for biomolecular engineering (BME) students. The class has recently been redesigned to give students experience with the entire process of DNA sequencing, from sampling to data analysis, using the latest nanopore devices from Oxford Nanopore Technologies (ONT) — a technology with roots at UC Santa Cruz.
Experience with the entire DNA sequencing process is very rare at the undergraduate level, exposing the students to valuable skills for their ongoing academic journeys and careers. Along the way, students not only get hands-on experience with sequencing, but learn the troubleshooting and iteration that come along with the research process.
“It’s not a class with a pure focus on technique,” said David Bernick, associate teaching professor of biomolecular engineering who leads the class. “It’s a focus on reasoning and logic and failure, and occasionally success. Students report that in this course they feel agency in their work — they can see that their choices matter a great deal.”
Experiential learning
BME 23L is the third class in a three-part series required for biomolecular engineering students, with the final installment now providing students with research experience. This past winter quarter was the first offering of the redesigned course, and a small class size allowed the students and professor to learn along the way.
For almost every student, it will be their first time carrying out the DNA sequencing process in action. Students read and learn about the processes through much of their courses, but now get to experience it hands on.
“This class is experiential learning in practice, something that’s quite important to us at Baskin Engineering and that allows students to realize their education and prepare for their careers beyond typical classwork,” said Alexander Wolf, Dean of the Baskin School of Engineering. “In this class, students learn that throughout the engineering design process, things may not always work as expected, but that initial failure can push us to persist, to iterate, and to find the best solution possible.”
Sequencing technique
A weekend field trip on the first week of the class brings the students to the salt flats to do sampling — filling up water bottles with the marsh water. The site is part of the Don Edwards National Wildlife Reserve, federal lands that allow for sampling with permits. Neither Bernick nor the students knew what organisms they would identify in that brackish, red water — but DNA sequencing allows them to find out.
To do this, the students go through a process to purify and extract DNA from the water, following a protocol written by Bernick. It’s always important to get the cleanest and longest pieces of DNA possible for sequencing, but particularly so with organisms coming from high-salt environments, something both the students and Bernick learned this quarter.
“I will say, I’ve never seen from student hands DNA as clean as what we were able to do,” Bernick said. “That’s a strong statement about the training they had coming in. We all learned how absolutely important it is to push the purification step to limits that I had not needed to do before.”
Preparing the DNA required several rounds of experimentation and iteration, finally achieving the unique long reads that nanopore devices can provide.
“That was pretty amazing to see, and it was very much hands on sequencing and getting reads that are incredibly long, which is really hard to do,” said Amanda Ferguson, a third-year BME and bioinformatics student who took the class in winter 2025. “It’s really cool to see something like that after you’ve put so much work in and done so much trial and error. It’s been very much a learning experience.”
Along the way, Bernick was advised by colleagues at the UCSC Genomics Institute who are experts in using nanopore devices, particularly Brandy McNulty, assistant director of genomics technologies at the UC Santa Sequencing Technology Center. McNulty shared advice, having faced a similar need to thoroughly purify DNA when sequencing human colon samples.
Then, the students feed the cleaned and purified DNA into the sequencing devices to be read. The class was able to use a new collection of MinION Mk1Ds provided by ONT, the company’s newest sequencing device that can perform long-read sequencing on a machine the size of a flip phone. When the winter 2025 section of the class ran, the devices were still unreleased to the general public.
The devices are available to students thanks to ONT’s educational program and the longstanding partnership between UCSC and ONT that dates back to the invention of nanopore sequencing, by BME Professors Emeriti David Deamer and Mark Akeson, along with a colleague at Harvard. The inventors’ ideas were licensed to ONT years ago and were foundational in the formation of the company, and the two institutions maintain a collaborative relationship as UCSC’s genomics experts develop new techniques and applications and ONT provides technical and educational support for their devices.
“To my knowledge, this course marks the first time an educator has deployed MinIONs across an entire teaching cohort at once,” said Jonathan Pugh, Director of Nanopore Education at ONT. “Working closely with David [Bernick] and his colleagues to enable this at UCSC was incredibly rewarding, considering the significant history between our two institutions. The feedback we’ve heard from students demonstrates just how impactful having these sequencers in the classroom has been.”
Students also had access to the computing resources on several recently-purchased Mac Mini computers, a capital investment by Dean Wolf to support sequencing education for undergrads.
Real results
These computing resources are needed to power the DNA assembly and analysis, the computer-science heavy final step in the sequencing process.
“It was really cool to see how sequencing goes from a wet lab process to a dry lab, because most people only work in one or the other,” said Emma Arbil, a third-year BME and bioinformatics student.
The students went through a rigorous analysis process to be able to confirm the identity of three organisms within their samples, each of which were extreme salt-loving archaea — a major class of microorganisms found everywhere on Earth from extreme environments to the human gut. Two other organisms did not fully match with any known species, meaning the students likely discovered at least two novel species.
These results can have a real-world impact in understanding the biodiversity of the local salt flat environment, where these understudied marsh environments are ripe for discovery. Students can publish the sequences they find online so other scientists can use their data. Any particularly interesting findings could potentially result in a published announcement paper.
“Environments like these high salt environments, they're really understudied,” Bernick said. “It's pretty likely that we're going to see something that's never been seen before.”
Overall, Bernick believes students leave the class with a better understanding of what can be done with their degree, and better prepared to face their academic journeys and their careers.
“Biomolecular engineering is a coalition between chemistry, biology, computer science, and mathematics, and it’s all those things converging that enable a new practitioner to go out into the world and be prepared for things that have not even been invented yet,” Bernick said. “That’s the magic that’s going on here.”
