New life found in Crim Dell

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February 24, 2009

1:04 AM

College of William and Mary freshmen participating in a national experiment funded by the Howard Hughes Medical Institute recently discovered what might be a new strain of bacteriophage, a virus that infects bacteria, in the Crim Dell.

The bacteriophage may provide a breakthrough in how phages work as well as insight into the treatment of diseases like tuberculosis.

The students, working through the Science Educational Alliance, a branch of HHMI that developed a two-semester research course known as the Phage Genomics Research Initiative, learned about scientific concepts while engaging in research.

The College is one of 12 institutions nationwide to participate in the national experiment.

In order to isolate bacteriophages, the students collected soil and water samples from the Crim Dell. The experiment was part of a larger attempt to determine the diversity of bacteriophage that infects the soil bacterium known as Mycobacterium Smegmatis.

Although the students conduct research on several parts of the campus, the only location where they found the unique phage was in the Crim Dell.

“When we realized that the phage was potentially unique, it was a very exciting moment,” Molly McDonough ’12 said. “For a lot of us, it was the moment that we really began to grasp that this lab is conducting authentic research that could make a contribution to this area of study. As novice researchers, that was an incredible feeling for us.”

Joe McClain, director of Research Communications of the College’s University Relations, said this discovery represents the potential of the College when it works together with national organizations.

Biology professor Kurt Williamson, who conducts the course along with biology professors Margaret Saha and Mark Forsyth, said the phages were isolated around the third week of classes last semester. Yet, since work is ongoing, it is difficult to determine exactly when this phage was discovered.

Forsyth said there are numerous benefits in finding new strains of bacteriophages, including using the organisms to help treat diseases that are traditionally cured with antibiotics, such as tuberculosis.

“The viruses we are isolating are lethal for a non-pathogenic relative of the bacterium, Mycobacterium tuberculosis, that causes tuberculosis,” Forsyth said. “As this devastating pathogen is becoming increasingly difficult to treat due to the acquisition of resistance to multiple antibiotics, it may be possible to use bacteriophage as an alternate means to treat the infection.”

Forsyth explained the series of steps taken to discover if the bacteriophage is in fact a new strain.

“We sent purified genomic DNA from one of our viruses, named CrimD, to the Joint Genome Institute at the Department of Energy National Lab in Los Alamos, N.M., in November,” Forsyth said. “They sequenced the virus entirely and we are now annotating the genome and comparing it to known viral DNA sequences in various databases and by various bioinformatic methods.”

Williamson said they already have preliminary proof that the bacteriophage is a new strain, but they will not know for sure until the DNA sequence is completed in a few weeks.

According to Williamson, a new bacteriophage genome sequence could lead to a new model to compare with other sequenced phage genomes.

“We could ask useful questions like: Which genes are common? Which are unique? Have genes been swapped around from this phage to other phage genomes, and with what frequency?” Williamson said. “Our phage may encode completely novel proteins and enzymes. That’s part of the excitement of discovery.”

Williamson said that about 500 phage genomes have been sequenced. Students isolated about 20 phages this past fall, but were only able to fully sequence one genome. The other 11 schools in SEA also are sequencing one phage genome, which means that a total of 62 different phages are all infecting the same organism.

“Considering the sheer abundance and genetic diversity of phages on the planet, each new phage genome that is sequenced represents a potentially rare discovery,” Williamson said.

McDonough said that they may have discovered more new strains of bacteriophages then they realize.

“In the phage lab, we were looking for more than one unique virus and we managed to isolate many that may potentially be unique,” McDonough said. “However, we were only able to send the DNA from one of them for sequencing, so that is the genome with which we are currently working.”

Williamson said this lab differs from a typical lab in that it engages students in genuine research typically reserved for professionals.

“Many introductory lab courses are implemented in a ‘cookbook’ fashion where students follow step-by-step instructions to arrive at predetermined results,” Williamson said. “This is misleading. It’s not real science, and it disconnects students from valuable lessons learned by troubleshooting and the thrills of genuine discovery.”

Williamson said studying phage genomics is particularly good for doing hands-on research.

The research lab consists of 27 freshmen. The students were selected based on a short application and an essay on why they wanted to participate. Because the students are working with real samples, three professors are needed to oversee the group.

“We teach this course because we love it,” Williamson said. “The level of dedication and quality of research produced by these [College] freshmen has been phenomenal. And since we are working with true unknowns, the course is just as exciting for the professors as it is for the students.”

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