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Young Biology Researchers Focus on Phages

It is safe to say that the 12 students this past semester in Nazir Barekzi's Phage Discovery and Genomics course in the Biological Sciences Department at Old Dominion University were not familiar with phages when their classes started in September.

What drew them to this first-of-its-kind course was a unique blend of collaboration and competition, and the opportunity it provided for undergraduates to do authentic research.

Anonymity is a defining characteristic of phages; these microscopic viruses can be found almost anywhere on Earth and make valuable contributions to the health of the planet, but very few people outside of life sciences know anything about them.

Scientists do know that lots of different types of phages exist - most in soil and bodies of water - but nobody has enough data yet to guess just how many there are.

What scientists and the medical profession have known for some time is that phages seem to be nature's secret weapon against bacterial infections and diseases. The study of phages started more than a century ago, spurred on by age-old anecdotal evidence, such as stories about people with cholera being cured after a dip in India's Ganges River.

Work at the Pasteur Institute in Paris in 1917 identified what came to be called "bacteriophages" (bacteria eaters). Each of the many types of phages is designed to literally hook-up with a specific bacterium, typically injecting its own DNA into the cell and replicating to the point that the bacterium bursts.

There were times in the early 20th century when phages were commonly used by physicians to kill bacteria and, because each phage is bacteria-specific, the right "dose" of phage can fight an infection or disease without causing damage to healthy cells. On the other hand, finding just the right phage for each purpose has always proven to be difficult. When modern antibiotics came along, they won out as the cheaper and more convenient weapon against bacteria.

But the fact that a bacterium cannot develop resistance to its parasitic phage, as is happening at a disturbing pace today with antibiotics, has boosted medical research involving these viruses and led to a program at the Howard Hughes Medical Institute in northern Virginia that is responsible for Barekzi's new course at ODU.

Barekzi, who is a biology lecturer, successfully applied to the Hughes Institute's Science Education Alliance to give ODU a chance to participate in the Phage Hunters Advancing Genomics and Evolutionary Science (PHAGES) project, which has enlisted select faculty and students from around the country in a broad study of phages. Professional scientists working alone in the hunt for phages could never cover the territory that thousands of students can. Barekzi describes it as "something like crowdsourcing" to turn up a lot of information in a hurry about these potentially very useful viruses.

"The course offers these ODU undergraduate students - all of whom are biology majors - an authentic research experience where they have total ownership of their projects," Barekzi explained.

The 12 students' first order of business was to pair up to conduct six separate projects, and their first chore was to collect soil samples. Some dug holes at construction sites on campus, another duo collected dirt at Mount Trashmore and still another got sandy soil from near the Virginia Beach oceanfront.

Each duo was hoping to sift through the soil to find phages - ideally one not yet identified and recorded by scientists - that would attack Mycobacterium tuberculosis, the bacterium that causes TB. This is a focus of the Hughes Institute PHAGES project, and any young researcher who finds a novel phage will be allowed to give it an official name.

In the end, each duo in Barekzi's class found a phage that showed signs of fitting the bill.

Keirra Dillard and James Johnson, both seniors, "enriched" their sample of campus soil by exposing it to mycobacterium. This process allows the few target phages that may be in a soil sample to quickly grow in number. Then the Dillard-Johnson team had a relatively easy time of it "purifying" their enriched product to isolate a target phage, which they propose to name "Akamu," a word they said means "from the earth."

Whereas Dillard and Johnson needed only eight purification procedures, the duo of juniors Nicole Northam and Briana McLaren had to work patiently through 23 such procedures to finally reach their target. In the end, however, their "Bricole" (combining their first names) phage produced the most promising gel electrophoresis results in preliminary DNA analysis, and the class chose it to be the one phage that best qualifies for further study.

At a showing Dec. 1 of posters from all of the projects, Northam wore the blue disco hat that went to the winning team. (The students in the class decided that phages, which have round heads and tails, look like disco dancers with Afro hairstyles, thus the theme of their "Phage Disco" poster show. Janis Doss, the doctoral student who assists Barekzi in the class, constructed Christmas ornaments shaped like phages as decorations for the show.)

Barekzi said he was very pleased with the way this first course turned out and is looking forward to what comes next. "The research experience will continue into a second semester, in the spring of 2015, where the students will learn to analyze a sequenced genome" of the Bricole phage. "The data will be collected on this phage and students will use bioinformatics to study the sequence and determine if it is a novel phage," he explained.

David Gauthier, assistant professor of biological sciences at ODU, will co-teach next semester's class.

The students seem just as excited as their instructor about the course. "Phage Discovery and Genomics has given me the opportunity to be able to do research and enjoy the work that I've done with my classmates. It's truly been an enjoyable experience working as a class to achieve our goals," Northam said.

For Dillard, a pre-pharmacy student, the class was a "rewarding" experience. "I was given the opportunity to use all of the skills and techniques that I have learned throughout my college years and apply it to my research. I am honored to be a part of the first class at Old Dominion University to explore this program."

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