As a college freshman, I could have taken the usual introductory biology lab where I may have dissected a crayfish, analyzed insect damage to trees using statistics, or measured the rate at which a particular enzyme works. These labs are designed to guide students step by step to produce results which teach students about important biological concepts. However, science does not always follow step-by-step instructions or produce predictable results. This is where the “Science Education Alliance-Phage Hunters Advancing Genomics and Evolutionary Science” (SEA-PHAGES) program finds its niche. Funded by the Howard Hughes Medical Institute, SEA-PHAGES gives undergraduate students an authentic research experience through isolating and analyzing the genomes of mycobacteriophages. I was given the opportunity to participate in the SEA-PHAGES program at Hope College, and it has challenged and propelled me farther into the world of biological research than I could have ever hoped.
A bacteriophage is a virus that infects bacteria. It is estimated that there are 10³¹ bacteriophages present on earth, making them ten times more prevalent than bacteria. They are continually infecting new bacteria and evolving which makes the bacteriophage population incredibly diverse. Since bacteriophages were first discovered in 1915, researchers have been isolating, and recently sequencing, the genomes of bacteriophage. They have found that each new genome sequenced contains new variations. One area of research has focused on mycobacteriophages, phage that infect hosts of the genus Mycobacterium. Through comparative genomics, researchers have discovered patterns of similar genes that allow mycobacteriophages to be classified into more than 20 distinct clusters. Several “singletons” have also been found with unique genomes that resist classification. This large and highly diverse population of mycobacteriophages presents the perfect model for studying genetic variation and virus-host relationships, all of which may help to uncover new techniques for understanding and diagnosing certain diseases.
Through the SEA-PHAGES program, undergraduate students directly contribute to this growing field of research. The SEA-PHAGES program studies mycobacteriophages using the host M. smegmatis, a harmless relative to the mycobacteria that causes tuberculosis and leprosy. Students start by collecting a soil sample and through a long process of enrichment, incubation, plating, and diluting, they isolate a single mycobacteriophage population. The DNA of each mycobacteriophage is then analyzed for potential cluster assignment using comparative gel electrophoresis. Finally, the genomes of potentially novel or otherwise intriguing phages are sent to be fully sequenced at facilities such as the Pittsburg Bacteriophage Institute. Students spend the next semester annotating the genome of a single phage by determining the start and stop codons for genes and assigning potential functions. All of the phages and their data are uploaded to PhagesDB, an online database of the 4,500 mycobacteriophages that have been isolated to date. Of these isolated phages, about 950 have been classified into clusters and 650 of their genomes have been completely sequenced, creating a rich source of information on mycobacteriophages that anyone can access.
From its start in 2008, the SEA-PHAGES program has grown to involve 70 schools across the U.S. along with several schools in other parts of the world. At Hope, my classmates and I along with nearly 1,400 other students from other schools are being prepared to make new strides in scientific research. Through the SEA-PHAGES program, we are learning basic lab techniques such as serial dilutions, gel electrophoresis, and DNA extraction. We are acquiring technical experience with programs used for bioinformatics and gaining a more complete understanding of genetics by applying it to real organisms. More importantly, we are making new contributions to the scientific community and thinking beyond a lab manual which may one day take us far beyond the world of mycobacteriophages.
For more information about Bacteriophage or the SEA-PHAGES program visit http://phagesdb.org/