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Student Research Shows Diversity of Bacterial Viruses

Summary

The Science Education Alliance is celebrating a major milestone with a scientific publication. The 192-author article is based on the work of students and faculty at the first 12 schools that offered its phage genomics course.

Jillian Walton entered the College of William & Mary intent on becoming a history major. Now on the verge of graduation, she is reading up on interdisciplinary molecular biology graduate programs and talking about the scientific paper she’s authored with students from around the country.

Walton’s change in direction resulted from her participation in an HHMI-sponsored genomics research course as a freshman. That year-long course—created by the Howard Hughes Medical Institute’s Science Education Alliance (SEA) and participating faculty—introduced Walton and her classmates to experimental science. Instead of plowing through textbooks, the students learned about biology by doing hands-on research on bacterial viruses called phages.

We really wanted to engage students early on in science. Faculty and students who participate in the course all say this is the best way to teach science.

Tuajuanda Jordan

The SEA is celebrating a major milestone with a scientific publication in the open access, peer-reviewed journal PLoS One. The 192-author article is based on the work of students and faculty at the first 12 schools that offered the National Genomics Research Initiative course, the first project launched under the SEA umbrella. The SEA seeks to serve as a national resource for undergraduate science education through the development, implementation, evaluation, and dissemination of novel teaching approaches aimed at broadening scientific understanding and participation.

The research paper, published in the January 27, 2011 issue of PLoS One, offers a look at the genetic diversity of phages uncovered by students who took the course. “I can’t believe work that I completed in an [introductory] laboratory course is being published,” says Walton, now a senior. “That one course has had such an impact on my life.”

In the first half of the course, the students, mostly freshman, isolated phages from soil collected from their local area then spent the rest of the term purifying and characterizing their phages and extracting its DNA. In the second half of the course, they learned to use bioinformatics tools to analyze and annotate the genomes from their phage. By next year, the course will be offered at more than 60 schools in 29 states and Puerto Rico. “We really wanted to engage students early on in science,” says Tuajuanda Jordan, the SEA’s director. “Faculty and students who participate in the course all say this is the best way to teach science.”

The PLoS One paper highlights the wide diversity of the newly-identified phages and provides insights into how these viruses compete with each other in the wild. “The students’ involvement in our research has done nothing to compromise the scientific questions we asked or the scientific accomplishments that we made,” says HHMI professor and University of Pittsburgh scientist Graham Hatfull. His work in developing the Phage Hunters program for high school students and undergraduates at the University of Pittsburgh served as the basis for HHMI’s phage discovery course and provided 6 of the 18 phages presented in the PLoS One paper. “These students are participating in authentic scientific research and … most would acknowledge that if a paper is published in a peer reviewed journal, then it represents important work.”

Most of the phages described in PLoS One were closely related to known phages’ genome sequences. This meant the students could place them into previously established categories, called “clusters,” on the phage genetic tree. But one phage was bigger and appeared entirely unique. The students from James Madison University in Harrisonburg, VA who discovered the phage named it LeBron after the famous Miami Heat basketball player who also stands out in the crowd. It was so novel, in fact, that it was assigned to its own cluster.

While it’s vital to look at these outliers, sometimes the most important discoveries come from comparing closely related phages, Hatfull says. “It’s easy to get trapped into thinking that the most interesting phages are the ones that are completely different,” Hatfull says. “But if we are going to get at evolutionary mechanisms, then we want to look at phages that display small variations as well.”

An exploration of the similarities found in closely-related phages—those in the A1 subcluster—demonstrates how phages stake out their territories. Once a phage of the A1 subcluster infects a bacterium, other A1 phages cannot infect the same bacteria, the paper shows. That immunity to co-infection arises because phages within a given subcluster produce a repressor protein that attaches to specific DNA sequences in the invading phage genomes and prevents them from infecting the same bacterium.

Surprisingly, an unrelated phage discovered under a redwood tree by students at the University of California, Santa Cruz, appears to have snagged a bit of DNA from an A1 phage. In doing so, that phage from cluster C, named LRRHood (Little Red Riding Hood), can produce the A1 repressor and prevent the A1 phage from infecting a bacterium it has already infected. “Its really remarkable,” Hatfull says. “This is the first example of apparent repressor theft that we are aware of in any characterized bacteriophage.”

The claims of uniqueness for LeBron, LRRHood, or any other phage may not last for long, as the SEA course is continuing to expand to more schools and more phages will be sequenced and analyzed. With that growth will come new opportunities to answer even more questions. “We can’t tell how geography plays into the types of phages that we find because the diversity is so high and our numbers are quite small. But we are on the verge of starting to look at those questions,” Hatfull says. “The SEA program makes it possible to acquire a large number of phages and analyze them in an organized fashion.”

Besides its important contributions to phage research, the SEA course has also shown that students learn science best by doing authentic research, and they are more likely to stay in science after being involved in research early. According to surveys of SEA participants, 89 percent of students are still pursuing a science major a year after taking the course. In comparison, only about 55 percent of freshman who participated in traditional laboratory courses are still on track to become science majors. Margaret Saha, a biology professor at William & Mary, says the phage program is especially good at retaining students from underrepresented groups who have historically had difficulty succeeding in biology. ”Phage lab has worked better than any other biology retention program,” Saha says. “It’s spawned so many discussions about how to teach [science] better.”

Arrykka Jackson, an author on the paper, says the experience has led her to pursue a career as a physician scientist. “It really helps you think about problems more broadly, and that’s a skill that can be translated to problem solving in all areas,” says Jackson, a junior at William & Mary.

The phage course also helps students understand that science is collaborative, rather than solitary. Each year, the course ends with a scientific symposium at HHMI’s Janelia Farm Research Campus in Ashburn, Virginia, where students present their work to faculty and fellow students. “It was quite an experience presenting at this meeting as a freshman—it really showed me how great it was to be part of the scientific community,” says Hannah Wang, now a junior biology major at the University of California, San Diego. “That’s when I realized that science isn’t just about finding or gaining knowledge, but it is about sharing knowledge, too.”

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