Dr. Paul Kirchberger, an assistant professor in Oklahoma State University’s Department of Microbiology and Molecular Genetics, has received an R35 MIRA from the National Institutes of Health to study how a group of microscopic, bacteria-killing viruses evolve and how they are built.

The five-year award, sponsored by the NIH’s National Institute of General Medical Sciences on Aug. 24, provides $1.25 million in federal funding to Kirchberger’s project, “Rules of Genome Evolution and Design in Small, Single-Stranded DNA Phages.”

The research focuses on viruses of bacteria, or bacteriophages, which infect and kill bacteria but are harmless to people. Kirchberger’s lab studies a specific group called single-stranded DNA microviruses, which he said are very abundant in the human microbiome and elsewhere. Yet scientists have been mostly unable to grow them in a lab.

"We know they're out there, but we can't study them in the lab," Kirchberger said.

The lab will start with a basic question: How do you grow them? Kirchberger wants to learn what these small viruses do differently from their larger competitors.

"For a virus, having a tiny genome requires completely different strategies to adapt to new challenges," Kirchberger said. "They have to do a lot with very little.

"But that simple genomic blueprint is then very attractive to us from a design standpoint. If we can figure out the 'rules' behind that, that means we can perhaps make our own phages to specifically target and kill bacteria of interest, antibiotic-resistant pathogens for example."

The five-year award will allow Kirchberger's lab to follow new leads as researchers learn more, which is important when so little is known about these viruses.

"We need to be able to go where the results lead us," Kirchberger said.

If researchers spot an interesting phage genome in existing data, they can try to grow the virus in their lab, exploratory work that Kirchberger said can be difficult to fund through other grants.

The work combines computational work, classical microbiology and synthetic biology. Kirchberger spends a lot of his time studying genome sequences on a computer, but the lab is working to turn those findings into experiments. Researchers can use computer data to synthesize small phage genomes, then introduce them into host bacteria to produce viruses they can study.

Graduate students handle plenty of the work in the lab, and Kirchberger hopes to hire more of them. Undergraduate students also learn in the lab, working alongside graduate students or leading smaller projects of their own.

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Story By: Colby Lewis | colby.t.lewis@okstate.edu