Genomics Research: First-Year Students Find the Phages
by Patricia Allen '13 (M.A.)
In the fall of 2009, a yearlong course plunged a group of freshman researchers into the uncharted territory of bacteriophages — also called phages — which are constantly evolving viruses that attack bacteria but do not harm people. Through a “Phage Safari” class, these first-year students started an inquiry-based study of genomics, the science that determines the DNA, or hereditary material, of an organism or virus.
It’s easy to marvel at the numbers associated with bacteriophages. An estimated one million populate just one-quarter teaspoon of seawater. Ubiquitous in the environment, they are always on the attack, infecting and destroying bacteria about one-septillion times per second. There are more phages on the planet than all other organisms combined, and the whole population turns over approximately every five or six days.
“This is a viral community that is perpetually changing,” says Christina King Smith, Ph.D., professor of biology, who team-teaches the course with Julia Lee-Soety, Ph.D., assistant professor of biology.
But perhaps what’s most surprising about these madly replicating viruses is that although they have been in existence for about two billion years, scientists have only completely sequenced the genomes of 1,000, according to Graham Hatfull, Ph.D., principal investigator of the Howard Hughes Medical Institute’s program known as SEA-PHAGES (Science Education Alliance-Phage Hunters Advancing Genomics and Evolutionary Science.) A national initiative, SEA-PHAGES funded the course at Saint Joseph’s for its first three years.
The course was so successful — there were more students than spaces available this past fall — it is now on the permanent roster at Saint Joseph’s.
“We realized the phage class was a very powerful teaching tool,” says King Smith. “Students are hungry for this kind of experience, where they are thinking like scientists, making real discoveries and contributing to a body of scientific knowledge. Developing strong analytical skills and learning how to be diligent when an experiment fails — and seeing the work through to completion — takes gumption. The fact that they pick up these skills and strengths in their first year of college is extraordinary.”
The students, who are mostly biology, environmental science and chemical biology majors, start their phage-finding odyssey by collecting soil samples from which they isolate their phage. They then purify and characterize it by using a variety of techniques, including electron microscopy and DNA analysis. At semester’s end, one or two phages are chosen to be sequenced, and the purified DNA samples are sent to a laboratory. In the spring, students use bioinformatics tools — advanced software — to annotate the DNA, which involves deciding where each gene starts and ends on the double-stranded helix.
Interest in phages extends beyond the classroom. “Phage therapy” has long been offered in Eastern Europe to treat drug-resistant infections, among other diseases. Several U.S. and international firms are investigating the health care applications of phage-based therapy. Which makes the work of King Smith, Lee-Soety and their students even more relevant.
But for now, both biologists are satisfied to point to their growing list of phage publications. “Starting with the first class, 53 phages have been successfully isolated,” says Lee-Soety, noting that the students give their discoveries whimsical names. “Along with Daisy, the first to be sequenced, phages BPBiebs31 and Flux have been published, and phage Winky has recently been submitted. DTDevon and Oaker, which were isolated from soil collected from animal enclosures at the Philadelphia Zoo last August, will follow at the end of the semester.”
Six down, with untold numbers to go.
Mycobacterium Phage Daisy
The first students enrolled in the course chose to sequence “Mycobacterium phage Daisy,” a class of phage that attacks the non-disease-causing form of the tuberculosis bacterium. Daisy was found in soil collected from a flowerbed on campus beside a concrete walkway between the Francis A. Drexel Library and the Science Center. Its fully sequenced and annotated genetic code is now held in GenBank, a DNA database of the National Center for Biotechnology Information, and is available to the growing numbers of researchers, like molecular geneticists, with an intense interest in how phages evolve across environments. All faculty and students involved in annotating Daisy are listed as co-authors.