Engineer helps ID genome of Rabbit Fever

Mar 11th, 2010 | By | Category: Campus News, Issue, March 11, 2010

As an electrical engineer, Khalid Sayood studies the need to efficiently store, manipulate and transmit large masses of information.

The UNL professor’s specialty – data compression – looks at how information is organized and then compacts the data so its applications, such as cell phones and computer programs, don’t become unwieldy. Now, a partnership with the University of Nebraska Medical Center has brought that work into a new area: microbiology.

Sayood and graduate student Ufuk Nalbantoglu were among a team of researchers from UNL and UNMC that recently annotated the genome of Francisella tularensis, a virulent bacteria causing the disease often referred to as Rabbit Fever.

The results of the work, published in February in the journal PLoS ONE, highlights a new effort by researchers in the NU system to team up to map a genome’s entire sequence.

Sayood
Sayood

“I’ve learned that one of the richest areas for examining how information is organized is in the biological sciences,” Sayood said. “How is it organized in DNA or in proteins? How is evolution reflected in that organization? There are vast questions out there to explore, so it’s exciting.”

A genome is made up of DNA, which has four different chemical building blocks called bases. In the Francisella tularensis genome sequenced by Nebraska researchers, about 2 million bases are arranged in a particular, unique order.

UNMC pathologist Steven Hinrichs, who heads the University of Nebraska Center for Biosecurity, was leading a lab effort to study the organism when he met Sayood about three years ago at a meeting organized by Prem Paul and Tom Rosenquist, vice chancellors for research at UNL and UNMC, respectively.

“(Sayood) said, ‘I’ve got an app for that,'” Hinrichs said.

The UNL and UNMC team worked with Los Alamos National Laboratory, which produced multiple copies of the tularensis genome that was broken into short random fragments. These fragments were reassembled into much longer but non-overlapping disjoint pieces called contigs.

Using software they developed, the UNL engineers determined in what order the various contigs should be arranged, then obtained short sequences that could be anchored to neighboring contigs. That allowed the biologists at UNMC and Los Alamos to bridge gaps between the contigs, Sayood said.

Nalbantoglu then annotated the genome, which requires decoding the sequence of letters into genes and other structural components of the genome and then using a similarity analysis to assign function to the genes.

“We now have the sequence,” Sayood said. “Now we need to know what it means.”

Hinrichs, who is an expert in biological threat organism diagnosis, has studied the bacterium for years, in part because of its viability as a bioweapon. The U.S. Army funds Hinrichs’ work to develop instruments and kits that would diagnose and test for tularemia in labs and in the field.

The initial findings from the genome sequencing suggest this specific strain of Francisella tularensis is a particularly static version, Hinrichs said. Unlike other strains of the bacteria, it shows little sign of evolving over time, he said.

That prompts questions about what causes some strains to change rapidly, while others remain the same. Hinrichs said he wants to know what environmental factors may be in play.

He’s also eager to continue working with Sayood and Nalbantoglu on future projects.

“It shows that our system is becoming on par with larger institutions,” Hinrichs said. “It’s a great example of cross-campus collaboration and it highlights a new capability for application of computational approaches to biology.”

– By Steve Smith, University Communications

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