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Home > ARRA Stories > Dr. Don Jarvis: Re-engineering Protein Factories
Dr. Don Jarvis: Re-engineering Protein Factories

By Susan Johnson

April 21, 2010

Don Jarvis, Ph.D., Professor of Molecular Biology, University of Wyoming

Mike Tiemeyer, Ph.D., Associate Professor of Biochemistry and Molecular Biology, University of Georgia.

Photo of Don Jarvis

Dr. Don Jarvis, Professor of Molecular Biology, University of Wyoming.

For many people, the word factory evokes images of workers on assembly lines, smokestacks, or robotic arms—not Petri dishes, moths, or viruses. But "factories" made of virus-infected moth cells have been used for nearly three decades to churn out large quantities of human-like proteins used in research and in medicines. Cell biologist Don Jarvis has spent most of his career trying to better understand and improve these cost-effective cellular factories. Now, with help from the American Recovery and Reinvestment Act (ARRA) and a new collaboration with molecular biologist Mike Tiemeyer, he's on the edge of a breakthrough.

Photo of Dr. Michael Tiemeyer

Dr. Michael Tiemeyer, Associate Professor of Biochemistry and Molecular Biology, University of Georgia.

The Problem: In this factory—called a baculovirus expression vector system, or BEVS—a specialized insect virus delivers genetic instructions to moth cells to make a specific protein. Because moths are very close to humans on the evolutionary tree of life, the proteins they make are nearly identical to those made by mammals such as humans—but moth cells can be grown faster and cheaper than mammalian cells in the lab. Jarvis estimates that BEVS has been used to make hundreds of thousands of different proteins over the years that have been vital in studies of basic biology and to make new medical products such as vaccines. However, as Jarvis and other scientists have discovered, there's a slight glitch in the system.

All cells, after they produce a protein, run the protein along a cellular "assembly line" that remodels the protein's basic structure into a wide array of new forms with an equally wide array of new functions. Moth cells simply do not remodel a given protein in the exact same way as mammalian cells would, even when the genetic instructions for making the protein are 100 percent identical. This leads to subtle changes in the proteins' behavior that can reduce their utility as research tools or medicines.

Photo of cells

Moth cells packed with virus particles. Moth cells can be turned into biological "factories" by viruses that deliver genetic instructions for making specific proteins. Such factories can produce large quantities of human-like proteins used for research and in medicines.

Finding a Solution: "We have a two-pronged approach," Jarvis says of his group's work on this problem. "To understand this system, and then to try to improve it."

Thanks to a new collaboration with Tiemeyer, of the University of Georgia's Complex Carbohydrate Research Center, Jarvis now has access to the expertise and high-powered technology he needs to see proteins' tiny, molecular-scale details. Tiemeyer's lab uses mass spectrometry, a fast, powerful technique that can decipher the secrets of obscure molecular structures.

These structural details will guide Jarvis' effort to re-engineer BEVS to make completely human-like proteins. With Tiemeyer's help, Jarvis is setting out to prove for the first time that subtle differences between the way a moth cell factory and a mammalian cell process the same protein can drastically affect the protein's ability to prevent disease as a vaccine—and that Jarvis can re-engineer BEVS to fix the problem.

"Nobody is studying this in any system," says Jarvis of the result of BEVS processing machinery on the effectiveness of vaccines. "It's simply amazing to me!"

Meanwhile, Tiemeyer's own work has benefited as well. When their collaboration began, Jarvis shared with him a special model fly, engineered to be molecularly similar to humans. Tiemeyer is using this model to study how individual sugar molecules that are added onto proteins during remodeling play an important role in universal cell processes involved in growth and cancer.

How This Funding Helps: This synergistic partnership is possible because of an ARRA-funded supplement from the National Institute of General Medical Sciences (NIGMS). The collaborators used the funds to hire two young researchers to serve as technology ambassadors between their labs.

"Without being able to focus one person on this project, it would have been spread out over six years," says Tiemeyer, who hired a postdoctoral researcher to analyze Jarvis' re-engineered BEVS proteins with mass spectrometry. "With his help, we've been able to get rapid progress."

"My long-term goal is to transfer this analytic technology to my lab," says Jarvis, who enlisted a young scientist to learn the Complex Carbohydrate Research Center's high-powered techniques and bring those skills back to Wyoming. "I don't even know what kind of equipment to look for. This has been a fantastic windfall for my work."

After Two Years: At the end of the two-year grant, Jarvis expects to have results that will resolve long-standing questions in the field of BEVS protein production. He will also improve his understanding of the details of BEVS protein processing and will have made significant progress in re-engineering the system so that it produces more human-like proteins.

Neither scientist thinks this rapid progress would have been possible without help from ARRA. "We always find ways of working on interesting questions," says Tiemeyer. "But without this funding, this work wouldn't have happened in a realistic time frame."

"The ARRA grant allowed for a quantum leap in our analytical capability," agrees Jarvis. "And without it, I wouldn't have had funding for this project. That's the bottom line."

Recovery Act Investment: The "N-Glycosylation Mechanism in Insect Cells" study received $273,064 in fiscal year 2009 from NIGMS.

Outside of the Lab

When not in the lab, Professor Don Jarvis can be found in the great outdoors. "I live in Wyoming," he says, "so naturally I love to do all those outdoorsy things: I'm a hiker, biker, fly fisherman, skier …"

Photo of Jarvis with a rainbow trout at  Wind River, Wyoming

Jarvis with a rainbow trout, Wind River, Wyoming.

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