Students participating in the SEA-PHAGES program have isolated more than 3,000 phage particles and identified where they found their phages using GPS. This map shows the sequenced phages according to their cluster type. Different clusters represent different genome types.Image courtesy of PhagesDBThe Howard Hughes Medical Institute's Science Education Alliance-PHAGES is a national experiment aimed at understanding whether beginning undergraduate students can make significant scientific discoveries while learning biology. According to a newly published analysis of the program, SEA-PHAGES students have published their scientific results, receive higher grades in their biology courses, are more likely to continue their education than overall student populations, and report an engagement in the process of science similar to what is reported by students who participate in “traditional” apprentice-based summer research.

The analysis, published February 4, 2014, in the journal mBio, uses five years of data gathered since HHMI launched the Science Education Alliance (SEA) Phage Hunters Advancing Genomics and Evolutionary Science (PHAGES) initiative in 2008. In the last five years, a total of 4,800 students at 73 colleges and universities nationwide have taken the SEA-PHAGES research course. Students in the course engage in authentic research and their findings contribute new insights about the diversity and evolution of phages, bacteria-infecting viruses that they isolate from soil samples. The analysis of course outcomes published in mBio provides evidence that the course engages students and motivates them to continue learning science.

The SEA-PHAGES course takes advantage of the tremendous biodiversity of bacteriophages, which remains largely unexplored. “There are an estimated 10³¹ phage particles in the biosphere—more than all other forms of life taken together,” says Graham Hatfull, an HHMI Professor at the University of Pittsburgh and a senior author of the mBio article. “For the most part, we do not know what the genes in phages do.”

But students participating in this national experiment in bacteriophage genomics are making real contributions to the field of genomics—by publishing peer-reviewed scientific papers (students were co-authors on 9 of 16 papers published by researchers in the program) and sequencing and analyzing the genomes more than 450 phage particles. As part of the course, students isolate, name, sequence, and analyze newly-discovered mycobacteriophages.

After isolating phages from soil samples, students visualize their phage with electron microscopy, then isolate and analyze that phage's DNA. Their data is submitted to an online database, where it is shared with the scientific community. Students are taught research methods, experimental design, and data interpretation that they apply to their own research.

“Phage diversity is so high that there is an extremely high chance that digging in the dirt will lead to something interesting and novel. Students may find some new genes, or they may find something completely unlike anything that's been described,” says Hatfull, who leads the SEA-PHAGES project in conjunction with HHMI’s Undergraduate and Graduate Programs group.

The Science Education Alliance at HHMI works with science educators at colleges and universities across the United States on pilot projects designed to advance science education on a national scale. The SEA helps form connections among individuals and institutions to turn good ideas into effective, scalable programs.

The SEA-PHAGES project began in 2008 under the direction of Tuajuanda Jordan, who is now Dean of the College of Arts and Science at Lewis & Clark College. Jordan and her team at HHMI, including Lucia Barker, Kevin Bradley, and Melvina Lewis, recruited an initial cohort of 12 schools in the fall of 2008, and the program has now blossomed to include more than 70 schools. The program is now directed by Cheryl Bailey, senior program officer at HHMI.

All students follow the same experimental procedures and work toward the same objectives, which Hatfull says encourages peer mentoring. But each student begins with their own soil sample and therefore isolates and studies a unique phage. “That project ownership engages students and gets them interested and excited about what they are doing,” Hatfull says. “It's their phage. If they don't characterize it, who will?”

Many kinds of research experiences can engage students and encourage them to pursue further education in science. But resources limit the availability of mentored, independent (or apprentice-based) research positions, and some course-based research experiences have limited reach as well; for example, some research experiences are offered only to high-achieving students and older students. In contrast, HHMI's Science Education Alliance has broadly implemented the PHAGES course, which is open to students with little or no experience in college-level biology at both four-year and community colleges. From 2008 to 2013, more than 4,800 undergraduates have taken the year-long course. This year, which is the sixth year of the course, more than 2,000 undergraduates are participating.

“You don't have to know a lot to get started on this project, yet the research is authentic and important,” Hatfull says. “This allows us to escape from the usual constraints of diversity that tend to exist in scientific communities, where you have to already be highly accomplished to be selected for research opportunities. This experience is much more open-door. All you need is curiosity and motivation.”

The SEA-PHAGES course is based on PHIRE (Phage Hunters Integrating Research and Education), a program Hatfull created in 2002 as an HHMI Professor at the University of Pittsburgh. Hatfull used the course as a way to involve high school students in his own research on phage genetics. HHMI's science education staff recognized the model's success in engaging students, and worked with Hatfull to adapt the program for the undergraduate classroom, designing a course that could be implemented on a broad scale without resident expertise in bacteriophage biology. Faculty at a cohort of 12 colleges and universities were trained to teach the course during the pilot phase of the project in 2008, and additional schools joined the initiative each year.

Since the program began, students have isolated over 3,000 bacteriophages from soil collected across the country and, in some cases, outside the contiguous United States. Students in the program have also analyzed the genomes of over 450 bacteriophages and contributed their data to the online databases GenBank and PhagesDB, and co-authored several peer-reviewed publications. But the true indicator of success for SEA-PHAGES, Hatfull says, goes well beyond the data. “Success is exciting the students, getting them to want to be involved. The course is a doorway to further engagement.”

Anecdotal evidence of that kind of engagement, he says, has been abundant. “Students in the SEA-PHAGES course get really involved and turned on to doing science. The anecdotal reports of student behavior totally blow you away: students come into the lab at odd hours; they're sad when the program ends. But as scientists, we're looking for hard, clear, quantitative data.”

The mBio publication offers that data. To evaluate the program, Hatfull and colleagues from HHMI and the SEA conducted several surveys and analyses. In one, they compared retention rates for students who participated in SEA-PHAGES at 20 institutions with overall retention rates at the same schools, as well as with overall retention rates of science, technology, engineering and math (STEM) students at those schools. Their data showed significantly higher retention rates—the percentage of first-year students who continued on to their second year at the institution—for SEA-PHAGES students than for either other group. These effects are similar to the boost in retention that has been reported for apprentice-based research experiences, they found.

The researchers used two methods to compare knowledge of biology concepts between students participating in SEA-PHAGES to peers who participated instead in a traditional laboratory course. One method involved evaluating the performance of biology students at six institutions that substituted the SEA-PHAGES course for a regular biology laboratory, comparing the grades of participating students in the accompanying lecture course to those of students who completed the regular biology laboratory. SEA-PHAGES students received significantly higher grades in the lecture course, averaging 2.95 on a 4.0 scale compared to an average of 2.58 for students who took traditional labs.

SEA-PHAGES students also scored as well as peers in traditional laboratory courses on a test of biological concepts administered both before and after the courses. The researchers conclude that although the SEA-PHAGES curriculum includes no specific instruction in concepts beyond those needed to complete the research project, students do not suffer from lack of exposure to subject matter. 

The team also compared SEA-PHAGES students' self-reported gains in learning, motivation and attitude, and career aspirations to those of students who participated in summer-long apprentice-based research programs. The SEA-PHAGES students scored as well as or better on the 20 components that were evaluated in both groups. Among the qualities that students were asked to assess were: understanding of the research process, tolerance for obstacles, data interpretation, and an understanding of how scientists think.

“Based on the anecdotal data, we would have been really surprised if we hadn't seen significant educational impacts,” Hatfull says. “But although the anecdotal experiences are compelling to hear, they are not as persuasive in convincing people. Now, if the program works as the data suggests it does, there should be little impediment to further expansion and continuing to enhance the program's impact.”