Prospecting for phage: Monmouth College students up to 11 discoveries in past five years

by Barry McNamara

Monmouth, Ill. (04/19/2023) — A common image from the California Gold Rush is a prospector panning in a stream.

For five years now, Monmouth College students have been on their own treasure hunts, trading a prospecting pan for a petri dish as they try to discover, identify and sequence new types of phage.

Phage are viruses that infect bacteria. It's "a biological entity," said Monmouth biology professor Eric Engstrom, stopping short of calling it an organism.

"The work is part of a nationwide discovery-based undergraduate research initiative. Other schools participating range from community colleges to larger research institutions, such as Johns Hopkins University. The Science Education Alliance-Phage Hunters Advancing Genomics and Evolutionary Science program provides support for the initiative. Also known, appropriately, as SEA-PHAGES, it is administered by the Howard Hughes Medical Institute and led by Graham Hatfull's laboratory at the University of Pittsburgh.

"They're fascinating things," said Engstrom. "There are an estimated one million species of animals, but we have no idea how many phages are out there. We are working to identify phages of actinobacteria, and there's nothing like this project for any other group of bacteria. It started with trying to identify phages that might be good for tuberculosis infections, but we're way beyond that now."

Undergraduate research

The project not only serves the purpose of what could be important scientific discoveries, but it also gives students the opportunity to do real-world research as early as the first semester of their freshman year.

"They're doing science," said Engstrom. "They're discovering things that weren't known in August."

Jaiden Rivera '25 of Lamoni, Iowa, was one of six students in Engstrom's phage discovery lab last semester. He recounted his breakthrough prospecting trip.

"It was a couple weeks into the fall semester," said Rivera. "I got it the second time I went out, just by myself. It was just a random spot near the asparagus at the (College's Educational) Farm, but I wrote down the coordinates. After I got back to the lab, it took another week until the phage started growing."

Once phage has been discovered and kept alive in the biology lab, the phage must still be purified, amplified and characterized by genome sequencing and electron microscopy. Following that, the information in the genome must be determined, described and classified, a process collectively known as "genome annotation."

"We need the interpretive information," said Engstrom. "Is there a gene here? Where does it start? What does it encode? Is everything in the genome that you absolutely have to have in there?" As the process progresses, "We're working on more nuanced questions."

Some of that work can be done by a computer, but it needs the human touch, as well.

"Software can only capture a part of it," said Engstrom. "It takes a pass at it, but it doesn't understand what phages are. It's pretty good at analyzing the DNA, but it's not perfect. There are parts where the computer thought there was a gene, but there likely wasn't. The human brain is needed to refine the picture."

At the end of last fall's course, a genomic DNA sequence for the two phages Monmouth students discovered was created at the University of Pittsburgh. That increased to 11 the number of phages that are on Monmouth's page in the national Actinobacteriophage Database.

"When we got the genome sequencing back, it was exciting to see it," said Rivera, who's worked on annotating his sample this semester. "When we got the picture of the phage was also exciting."

"A phage is a bit abstract until you get a picture back and see it," added Engstrom.

On April 18, "We submitted the annotation of one of the phages for publication today," said Engstrom. "It still has to get past quality control, but I'm pretty confident that we did a good job."

Continuing partnership

This fall, as the partnership moves beyond its initial five years, all students enrolled in the College's "Introduction to Evolution, Ecology and Diversity" course will also be enrolled in the Phage Discovery Lab.

"So we are not only continuing the lab, but expanding the number of students who can participate in it," said Engstrom. "We committed to this five years ago, and we found three the first year. We got off to a rockin' start. This is working."

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