Pitt, Einstein College of Medicine Professors Find "Largest Unexplored Reservoir of Gene Sequence Information" in Bacteriophages

Contact: Abe Habenstreit

Albert Einstein College of Medicine

[718-430-3601; habenstr@aecom.yu.edu]

PITTSBURGH and NEW YORK—The largest unexplored reservoir of gene sequence information in the world may be contained in bacteriophages, viruses that infect bacteria, according to a paper by researchers at the University of Pittsburgh, Albert Einstein College of Medicine, the Tuberculosis Research Center of India, and two American high schools, as reported in a paper published in the April 18 edition of Cell.

Characterizing the genomes of 10 new mycobacteriophages for the study revealed an astounding number of never-before seen genes, according to principal investigators Graham Hatfull, Roger Hendrix, and Jeffrey Lawrence at Pitt, and William R. Jacobs Jr., professor of microbiology and immunology and of molecular genetics and a Howard Hughes Medical Institute (HHMI) investigator at Einstein College.

The Pitt faculty are all in the Department of Biological Sciences, where Hatfull is an HHMI Professor and Eberly Family Professor of Biotechnology, Hendrix is a professor of biological sciences, and Lawrence is an associate professor.

The researchers found that 50 percent of the genes in the mycobacteriophages they studied had never been seen previously and that 80 percent of the remaining 50 percent had been found only on the 14 mycobacteriophages that have been sequenced to date.

Bacteriophages, viruses that infect bacteria, are the most abundant organisms on the planet, with estimates as to the number of different species at ten million trillion trillion, or 1031. No genomically defined phage has been isolated more than once, and the few sequenced phage genomes are widely varied, according to the authors.

"The genomic sequences of these newly isolated mycobacteriophages suggest that the bacteriophage population as a whole is amazingly diverse," said Hatfull. "There is some suggestion that phages could be involved in bacterial pathogenesis in ways we never imagined."

One of the phages studied contained a gene homologous to the human gene in lupus, according to Jacobs. "While we don't yet know the function of this protein, we're pretty confident that it will lead us to better understanding of lupus. Many autoimmune diseases have infectious origins—lupus may also."

The researchers conducted their work with the aid of high school students from Pelham Memorial High School in Pelham, N.Y., and Greater Latrobe High School in Latrobe, Pa. The participating students, who are listed as coauthors of the paper, were part of a science educational program established by the Howard Hughes Medical Institute. In the project, the high school students gathered the samples, participated in the purification of the phages and the isolation of DNA, and assisted in the electron microscopy.

"While much of the nuts and bolts of the sequencing was done by folks here in our genome center, the students also participated in the analysis of the DNA sequence and annotation of the genomes," according to Hatfull. The Pittsburgh Bacteriophage Institute, one of the world's leading centers for bacteriophage genomics and codirected by Hatfull and Hendrix, provides an excellent environment for student researchers.

Hatfull and Jacobs are staunch supporters of getting students involved in science, as opposed to just teaching them, as a way to cultivate intellectual curiosity in science.

"We envisioned this program could be used all across the world, because it gets the students involved in meaningful projects," said Jacobs.

"When you examine what it takes to get high school students involved-the difference between a good project and a bad project—it comes down to a sense of ownership," added Hatfull. "Because the students are able to locate and identify the genes, and when they find a new phage, they are able to name it. That will be the name that the entire scientific community will use to refer to that phage from then on."

The sheer number of phages and their amazing diversity virtually assures that any high school student involved in the program will discover his or her "own" phage, according to Hatfull.

The names for identified phages range from the scientific-sounding L5 and Che8 to the whimsical Barnyard and Rosebush. And although Bxb1 and Bxz1 sound technical, they are named respectively as Bronx bomber 1 (obviously named by a New York Yankees fanatic) and Bronx Zoo. Coincidentally, Bxz1, collected during a trip to the Bronx Zoo, was the phage that contained the lupus-like gene.

The real added bonus for the students was inclusion as coauthors of a scientific paper in a professional journal like Cell.

"It's very unusual to have high school students listed as coauthors," said Dorit Zuk, acting editor at Cell and editor of Molecular Cell.

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4/22/03kwh