Melody Neely, associate professor of biological sciences at the University of Maine, instructs a student in the Phage Genomics class. (Courtesy of the University of Maine)

In Phage Genomics at the University of Maine, students can go from playing with dirt to being published scientists over the course of two semesters.

Despite being academically challenging and time intensive, Phage Genomics, or simply “Phage,” as the students know it, is almost universally beloved by those who have taken it. Since its founding, the course has not only led to over 46 published genomes and five published scientific papers that students have co-authored, but also an enduring community of students and peer mentorship network that is only getting stronger with the class’ recent designation as a Research Learning Experience and opening up to students beyond the Honors College.

Phage is taught by Sally Molloy, associate professor of genomics; Melissa Maginnis, associate professor of microbiology; and Melody Neely, associate professor of molecular and biomedical sciences. The class, which is part of a nationwide program sponsored by the Howard Hughes Medical Institute, is required for all incoming and transfer students in the Department of Molecular and Biomedical Sciences. 

Over the course of two semesters, Phage teaches students about bacteriophages, or viruses that infect bacterial hosts. Bacteriophages are considered the most numerous biological entities on Earth. For every bacterium, of which there are an estimated five million trillion trillion on Earth, scientists estimate there are approximately 10 phages that can attack it.

Studying how these viruses affect bacteria is important because it can help develop viral treatments and inform scientists’ understanding how viruses and bacteria interact, which is essential to understanding human health.

On top of traditional lectures and classwork, students in Phage have the opportunity to isolate their own bacteriophages from soil samples, which they often collect and bring in. Because bacteriophages are so common and microbial life in soil is so active, the amount of scientific discovery available to students is seemingly endless. 

The Phage journey begins in a one-week Black Bear Bridge RLE course called Rage of Phage before the start of the fall semester. Students isolate genomic DNA from pathogenic mycobacteria, which is sent to a sequencing facility. In the fall Phage class, the students assemble the bacterial genomes and search for prophages, which are bacteriophage genomes that have integrated into the bacterial genome and potentially impact the virulence of the bacterium. Students also isolate phages from the soil and name them (which always result in a variety of quirky monikers, like NiceHouse, MrRager and IdentityCrisis). The genomes of the newly isolated bacteriophages are sequenced over the winter break so that in the spring semester, students can characterize the genomes of both the prophages and bacteriophages by identifying genes, determining their function and learning about how the viruses impact the biology of their bacterial hosts.

Because the students are working with real materials instead of controlled experiments, things don’t always work out as planned — not all the prophages that are isolated in the first semester make it to the spring — but that failure is part of the learning process.

“We’re taking away from the mindset of, ‘I have to get an A,’ to ‘I can fail at something and learn from it and come back and do it better,’” Neely says. “You have to get it wrong before you get it right. That’s such a foreign idea to students coming into science.”

The students’ completed phage genomes are all housed on an online database, but they also have the potential to be published in academic journals. In total since the class started in 2011, 46 phage genomes have been published out of work that UMaine students did in the class. For the first time, the 2021 cohort of the Phage class has five previously unidentified phages published in their own scientific papers: Oregano, Periwinkle, Finkle, Widow and StarStruck

Dorian Royal is a current junior biochemistry major who worked on the phage Oregano. He took the class because he was interested in the practical elements and impact of doing research on health and curing disease (though he says he had no idea that he could get published when he signed up for the class, an opportunity that he was “very grateful” for).  

“Instead of just learning stuff from a book and memorizing it, you’re applying and observing what you learn,” Royal says. “You are able to see, ‘Oh yeah, what I’m doing is really working.’ Having research that you’re able to call your own is a really validating feeling.”

Royal is also a football player, and says that as an instructor, Molloy was supportive and accommodating with his schedule traveling for games — which could be tricky, as the class meets for four hours twice a week in the fall and three times a week during the spring. 

“I don’t think it would have been as overwhelming as it could have been if I didn’t have that support,” Royal says. “It was really validating seeing Sally [Molloy] was always on my side and pushing me to always perform at my best.”

Because of the skills he built in the class and relationship he developed with Molloy, Royal has continued his work with phages in Molloy’s lab this year. 

The Phage professors are committed to making the challenging class possible for any student who is interested and committed to taking it. Sophomore Alison Kueck was even able to publish the phage she worked on in class, Periwinkle, after only taking Phage in the spring semester. She transferred into the molecular and cellular biology major from the medical laboratory science major (after a chance conversation with Molloy in the hallway, no less). After catching up on the material over winter break, Kueck was able to jump right in – with the support of Molloy, her classmates and the devoted teaching assistants, of course.  

“It’s the coolest class I’ve ever taken,” Kueck says. “It was so interesting to see something that I was working on that mattered. I’ve taken a million science courses and you’re regurgitating the same experiment and it goes in the trash at the end of the day. Getting published was amazing as well. I mean, how many kids get published at 18 or 19?”

Though HHMI designed the scientific process for isolating the phages, the Phage instructors have adapted the curriculum in other ways to support a more holistic approach to scientific learning. For example, Molloy says she will have students form groups in class to discuss and sometimes illustrate the topics covered; they even create group contracts with rules about how they’re going to interact with one another. 

The instructors also have students write reflective essays about their experience at the end of every week that the instructors read and write notes to students in response.

“We’re giving them lots of experiences in this class but if you don’t stop to think about those experiences in a detailed manner you don’t learn from those experiences,” Molloy says. “We’ve got to develop the space where trying new skills feels like a normal part of the process in a community where people are going to support you at your best and at your worst.”

Alan Baez Vazquez graduated in 2020 with a degree in biochemistry and is now pursuing his Ph.D. at Harvard University (in large part, he says, because Phage opened his eyes to the possibility of making scientific research a career). He says that the journaling assignments were surprisingly helpful when he was choosing graduate programs.

“That was the first time I ever had to talk about my feelings in a science class,” Vazquez says. “When you go out and get a Ph.D., a big part is finding a healthy lab environment, so being in touch with, ‘Oh, failure sucks in the lab, I need a support network to carry me through these failures’ is definitely very helpful.”

The mentorship element of the course is unique, too. Aside from the mentorship of Molloy, Maginnis, and Neely, the class has an unusually high number of teaching assistants — up to seven at a time for a class of 25 — and most of them are undergraduate students who had previously taken the Phage course. 

The TAs have a community, too. Seniors Aiden Pike and Kate Southworth are not only currently teaching assistants in the Phage course, but they also took Phage together their freshman year.

“I think the most important part of this class was the sense of community,” Pike says. “It is something that has kept me going through this degree.”

The mentorship element of Phage has, perhaps, been more important this year than ever.

“I feel like a lot of students have been having anxieties coming into this year, especially after COVID,” Southworth says. “A lot of what we do involves helping students feel supported and getting them the resources they need so the transition is easier for them. It’s been an awesome feeling knowing you are helping them out.”

Other past Phage students will teach office hours-style sessions outside of class called Phage Enrichment that are popular with current students (Kueck says that when she took the class, she attended Phage Enrichment every week).

“If you don’t understand the material, it’s not like you’re thrown out to the sharks. You have a chance to learn from each other,” says sophomore Eleanor Carrolton, a Phage enrichment instructor. “I didn’t understand ribosomes the first time and now I have a way to explain it to other people that’s more understandable.”

The experience has an impact on the student teachers, too. Vazquez said that being a TA for the Phage class his senior year of undergraduate prepared him for teaching as a graduate student. Southworth says that her experience as a Phage teaching assistant has solidified her decision to pursue an M.D./Ph.D., and Carrolton is considering becoming a professor when she previously wanted to focus solely on lab work.

This year, Phage was taught both semesters as an RLE, which has given the instructors more resources from that to help run the mentoring element of the course. 

“We want students to learn that they don’t have to be alone in any of their challenges, they can collaborate with each other, with faculty and within that community,” Molloy says. “We’re mirroring how it really is when you’re doing challenging research and learning. We don’t go up in our labs and by ourselves never discuss or talk to each other. That’s not how anything works and that’s not how the education system should work. We’re an R1 school. We want students to have access to the authentic research that UMaine can offer.”