Earlham College | News from Public Affairs

RICHMOND, Ind. — Christmas comes Aug. 1 this year for Earlham College Assistant Professor of Biology Peter Blair and dozens of Earlham science majors.

Peter Blair with Doug Armour and Caroline Hackett

Classmates and fellow Texans Doug Armour ’07 and Caroline Hackett ’07 are among the Earlham students who will assist Assistant Professor of Biology Peter Blair (center) with a study of the rodent malaria genome plasmodium yoelii. The research aims to validate experimentally the existing, largely computational prediction of the “finished” genome.

That’s the day the College can expect to receive more than $164,000 from the National Institutes of Health (NIH) for a three-year research project with potential bearing on the development of a malaria vaccine.

Malaria remains among the world’s deadliest diseases, causing some two million deaths annually. With the new grant — the College’s first-ever from the NIH — Blair will initiate a program putting biology and biochemistry majors on the trail of incorrectly predicted gene models in the Plasmodium yoelii malaria genome.

A major share of the grant will acquire an automated DNA sequencer for Earlham’s science facilities. Blair estimates that between six and eight upper-class science students each year will use the roughly $100,000 machine to test experimentally for errors in computational predictions of the Plasmodium yoelii genome. (He is just completing a “mini” proposal to another grant-making organization that, if approved, would cover $50,000 of the sequencer’s price tag and make more of the NIH funding available for other components of the program.)

While scientists in the last decade hailed the publication of a number of “complete” genomes, including Plasmodium yoelii and especially — in 2003 — the human genome, Blair cautions that when a genome is referred to as finished, it really only means that study of the functional genomics of that organism is “off to a good start.”

During fall semester 2005, students in Blair’s immunology course did research — political and socioeconomic, as well as scientific — into the effects of a possible bird flu pandemic.

“A finished genome is more like a leaping pad,” says Blair, who did post-doctoral work in molecular and genomic parasitology at the Naval Medical Research Center in Silver Spring, Md., before joining Earlham’s faculty in 2004. He explains that gene structures in a published genome are put together using various predictive computational algorithms and are subject to error. Even though well better than 99 percent of the DNA sequence “probably is accurate,” Blair says the challenge ultimately becomes where coding regions begin and end.

“Every genome that’s published can use refinement,” Blair says, adding that the primary goals of the NIH study will be determining what are known as the exon and intron boundaries of certain gene structures and verifying “coding frames” in Plasmodium yoelii.

Through plasmodb.org — a University of Pennsylvania-supported Web site, the Earlham team will be able to constantly update malaria researchers on its experimental validation of various gene structures, says Blair. “What we want is to have a researcher who’s investigating a portion of the sequence be able to look and say, ‘Oh, the group at Earlham checked this and so I can have confidence that it’s accurate.’ That way, there should be fewer concerns and experimental roadblocks” as others pioneer the path toward a hoped-for cure.

The process will begin with more “computer mining” of established malaria data sets, explains Blair. He and his students will examine closely both existing and emerging computer models for the Plasmodium yoelii genome, trying to locate potential errors, then move to the wet lab — with its new DNA sequencer — to verify their findings using modern molecular methods.

According to Blair, a recent pilot study of the NIH research proposal by students Caroline Hackett ’07 and Doug Armour ’07 suggests the project may be extremely rewarding.

Armour and Hackett reported — at undergraduate science conferences this spring at Earlham and Butler University, respectively — on experiments involving short fragments of DNA known as expressed sequence tags (EST). A survey by the pair of about 500 ESTs yielded 10 “candidate” genes for experimental validation and of those, Blair says, only two of the predicted gene models proved correct.

“A few had to be corrected or refined,” continues Blair, “and there were a couple that were potentially ‘novel,’ or genes not predicted by the algorithm at all. That’s another major goal of our project, to maybe find some of those novel genes.”

Although Armour and Hackett tested the human malaria strain Plasmodium falciparum — the infectious disease’s most common and deadly form — the upcoming Earlham study will switch to Plasmodium yoelii, a rodent malaria. The change is a strategic move, Blair says, that promises to contribute valuable information to science while at the same time establishing a competitive niche for Earlham among its peer group of liberal arts colleges.

Both genomes have been recorded, says Blair. But, the “sequence coverage” or accuracy rate is considerably higher for Plasmodium falciparum, precisely because it is the number one malaria killer and, consequently, gets most of the attention (and money) in major government and university-based research labs across the country.

“That’s why we’re tracking the rodent type; because it needs the most help,” Blair says. He notes that the rodent model is used throughout the medical research community and has made countless important contributions to the development of new treatments for illness and disease. Still, it also can be “less competitive” — in terms of the demands on infrastructure, staff resources and dollars — than, say, the Plasmodium falciparum work being done elsewhere.

“And that’s why we can do this at Earlham. In fact, it’s perfect for a place like Earlham, with its reputation for really excellent science involving undergraduates,” observes Blair. He anticipates the success of the upcoming NIH study may lead science programs at some other independent liberal arts colleges to try to emulate Earlham’s approach, particularly as they consider the current evolution in biology by incorporating genomics and bioinformatics (computational-based biology) in their curriculum.

“It’s certainly helped to get us on the radar with a new funding source, the malaria research community and many new prospective students,” Blair says.

Contact:
Peter Blair, assistant professor of biology
765/983-1517 — E-Mail Peter