Purdue Today

New seekers: Undergraduates discover new viruses, sequence genome

Editor's note: This story originally appeared in the Summer 2011 issue of Agricultures Magazine. The magazine may be viewed at www.agriculture.purdue.edu/agricultures.

Just a couple years ago, students now in Jenna Rickus' genomics class were anxiously awaiting college acceptance letters.

Today, they're knee-deep -- literally in some cases -- in the genomes of bacteriophages, viruses that infect and live off bacteria. Their research will be available to scientists all over the world.

"You wouldn't expect someone who's 19 to be sequencing genomes," says sophomore Leah Liston, a biological engineering major from Arlington Heights, Ill. "I didn't expect it."

Purdue is among a small group of institutions selected by the Howard Hughes Medical Institute's Science Education Alliance to offer the National Genomics Research Initiative, a two-semester course developed to give undergraduate students experiences in scientific discovery. The course was offered for the first time at Purdue during the 2010-11 academic year.

"These opportunities didn't exist when I was a student," says Rickus, associate professor of agricultural and biological engineering, who team teaches the course with Kari Clase, an assistant professor and biotechnology researcher in Purdue's Industrial Technology program. "Technologies and discoveries today are moving so quickly that we have to give students research opportunities much sooner."
  
Clase says teaching students how to conduct research via a lecture or even a traditional laboratory format just isn't the same as having them jump in feet first. "We've tried to bring research into the classroom, but you can only do that in bits and pieces," she says. "Here, they get to see how science actually works. This is multiple universities working on a project at a national level. That's how research is conducted."

In the NGRI, students isolate and characterize their own bacteriophages  -- or phages -- from local soil. From these phages, one is chosen to have its DNA sequenced and annotated.

Bacteriophages are expected to play a role in a variety of scientific fields. It's possible that phages could help attack antibiotic-resistant and harmful bacteria. Scientists also study phages for use in controlling foodborne bacteria, such as E. coli and Listeria.

Digging around

The Purdue students started at square one -- in the soil -- looking for a bacteriophage. Bacteriophages are among the most abundant forms of life on earth, so finding them should be relatively easy.

Tell that to Sean Kearney.

"We looked in eight places before we found one," says Kearney, a biological engineering and applied mathematics major from Carmel, Ind.

Students dug around numerous places on and off campus looking for bacteriophages, which are present in many types of soils. Some took samples from the mud under the Wabash River. Emilia Czyszczon, a biological engineering major from Chicago, took a boat on an underground river, scraping glacial mud from the cave wall.

Once students had determined through lab tests that their sample had a bacteriophage, they had to purify it, get it down to a single phage, grow the phage in a petri dish and then view it through electron microscopy. The process can be daunting, but upon completion students get to do one of the least scientific and most student-like portions of the project. They name their phages.

This year, students welcomed Angercorn, Eraiser, RiverMonster and Czysczczon1, among others, into their labs and microscopes, and more broadly, into the scientific community. See all the phages discovered at https://phagesdb.org/institutions/PURD/.

But as soon as they felt relief at having discovered a phage, the next step -- genome sequencing -- began.

Students extracted DNA from one phage and sent it out for sequencing. (The process is expensive, and the program provided funding for only one.) The lucky phage selected was MrGordo, discovered by Kearney in a flower bed by the Agricultural and Biological Engineering Building.

As real as it gets

All of this was done under the watchful eyes of Rickus and Clase. But here's the catch: They were willing to let students fail. "They have to make their own decisions, determine all the things that have to be done," Rickus says. "Bringing research like this into the classroom, in this way, makes students use critical-thinking skills."

During class time, students receive instruction on how to purify a sample, for example. But there are several different ways to do that. They evaluate the strengths and weaknesses of each purification method and decide which they'll use. If they choose the wrong method, they could find themselves back in the mud scavenging for another sample.

The idea is to mimic a laboratory setting, where you have knowledge, but there isn't a teacher at the front of the classroom to fall back on if you don't know the answer. And not everything was outlined in the lab manual. "We'd have to decide what to do," says Kayla Fouch, a biology major from Brownsburg, Ind. "We had to determine our own steps, and that definitely affected our progress."

The fear of uncertainty was there, for sure, but many of the students found that exhilarating.

"You're practicing a lot of lab techniques that you don't get to do in a regular biology lab," Kearney says. "It's exciting because you're working on a project with clear implications, which is not something I expected to do so early in my undergraduate career."

Once students have sequenced their genomes, they can compare them to other known bacteriophage genomes, group them and start categorizing and identifying the genes.

"They've got to take it further. They've got to look at the genome and make sense of it," Rickus says. "Today's students have to be savvy in understanding and manipulating genomic data."

Understanding that data inevitably requires judgment calls. Because there's not one right answer, students must think critically about their work. "They can sit at a computer and look at the genome and make individual calls," Clase says. "That's a unique opportunity that goes way beyond science."

Why it matters

Once all the data is collected and analyzed, it will be deposited in GenBank, the National Institutes of Health's genetic sequence database. Once there, it will be available for scientists around the world to study or use as needed.

Since there is an almost unthinkable number of bacteriophages on earth, it will take time to understand different types and their biological processes. Through this class, Purdue students are adding at least one piece to the puzzle.

Czyszczon discovered a virus that kills a form of bacteria similar to tuberculosis and leprosy. "It would be cool to see if my bacteriophage could be a stepping stone to finding a treatment for tuberculosis," she says.

Fouch, who is interested in biological research, says she now has a new perspective on her studies. "It gives you a good idea of what being a research scientist is like -- the pressures, the deadlines," she says. "It's a starting point for future research."

Maddy Cox, a biological engineering major from Ballwin, Mo., credits the class with helping narrow her focus from a broader range of topics. "I didn't know what I wanted to do with biological engineering. Now, I have a better idea of the opportunities out there."

Rickus is pleased that the research experience has had a positive effect on how her students are learning and in helping them determine what they want to do when they leave school. "We've seen a lot of these students pursuing other research opportunities," Rickus says. "It's definitely affected their future path."

This type of outcome is central to the NGRI. "We're helping to bring up a new generation of students who love research and want to become scientists," says Tuajuanda Jordan, director of HHMI's Scientific Education Alliance. 

Students from Purdue's first NGRI course hope that others will follow in their footsteps. Kearney says taking the class early on can help you determine if you want a career in research or, conversely, if it's not for you. "I wish you could take this as a freshman."