Learning Something from Nothing

The Virginia Tech Center for Genomics studies how tiny organisms endure hardship

by Michael Sutphin

Few homeowners realize that a tiny, single-celled organism causes the black streaks on their roof shingles. But when researchers with the Virginia Tech Center for Genomics (VIGEN) put the discolored shingles under a microscope, they saw a land-dwelling cyanobacterium of the genus Gloeocapsa. A thick barrier outside a community of these cells protects the organisms from dehydration, high levels of UV radiation, hot temperatures, and heavy metals such as copper and zinc.

Since 1996, Malcolm Potts and Richard Helm, both faculty members in the Department of Biochemistry, have used their combined expertise to study organisms like Gloeocapsa. As they learn more about such organisms, they hope to better understand the capabilities of human cells and how this knowledge could improve emergency medicine, extend vaccine and blood storage times, and just possibly, slow aging.

“Basically, we study how to get away with nothing,” Helm says.

That’s how Helm describes their work at VIGEN, where he and Potts investigate how cells survive extreme conditions such as desiccation. Grocery stores sell a familiar example of desiccated cells: yeast, a single-celled fungus preserved as a powder. How does yeast endure almost complete water loss? Can mammalian cells survive such a process? These questions prompted the team to investigate the possibility of drying human cells. In 1998, with funding from the Office of Naval Research (ONR) and the Defense Advanced Research Projects Agency (DARPA), they began working toward this goal.

The funding agencies as well as Helm and Potts realized that
this type of research could lead to significant advances in medical technology: Hospitals could store blood at room temperature for extended periods of time. Researchers could extract stem cells from an umbilical cord, preserving them for years until the infant, now an adolescent or adult, needs them to re-grow tissue. “We knew that these advances in blood storage and personalized medicine were way out there in the future,” Helm says. “So we started by trying to take the strategies that microbes use and apply them to mammalian cells.”

After months of submitting human kidney cells to desiccation, the research team reached a dead end. “With all the work we did, what we found was it seemed like you could not dry a mammalian cell,” Helm says.

But wait; think back to those cyanobacterium cells. What would happen if human cells were in a “community?” Although preserving human cells by drying them in isolation seemed impossible, preserving multiple cells at the same time did not. Helm says many types of human cells can be grown in small aggregates, or spheroids, and if caught at the right time, these aggregates can be stored at room temperature for several weeks. “We took containers of these human cells with us in airplanes, cars, and meetings with other researchers just to show that it was possible,” he says. “We would take them back to the lab when we returned from our trips and our team would return the well-traveled cells to their normal growth pattern.”

“What we are attempting to get these cells to do is not divide,” Helm continues. “Cell division is the dangerous part of your cells’ existence, and if we can reduce the rate at which this occurs, we can increase the functional lifespan of the stored cells.”

Neurons, or impulse-conducting cells in the brain, spinal cord, and nerves, are examples of animal cells with halted cell division. “The neurons you have now are the same ones you had as a child,” Helm explains. He adds that by slowing down the rate of cell division, researchers might one day be able to increase a human’s lifespan,
leading to further research on longevity and aging.

“The cyanobacterium on the roof of your house has managed to occupy a niche that we would find completely inhospitable,” Helm explains. “In order to survive, it invokes a coordinated shutdown and restart process. Understanding the mechanisms of this event will lend insight into how more complex organisms such as ourselves control similar processes.”

From the roof-dwelling cyanobacteria, to yeast, to human cells, and now to tiny soil-dwelling worms called nematodes, Helm and Potts have spent a decade in collaboration, investigating how organisms
survive the harshest conditions in the hopes that one day, in that golden hour when a trauma victim must receive medical care, their work might lengthen this “window of time” or hospitals might be able to store blood products for years, not months, and at roomtemperature. As their research progresses, so too will
the possibilities.

For more information about the Virginia Tech Center for Genomics, visit http://vigen.biochem.vt.edu.

Malcolm Potts and Richard Helm

Biochemistry professors Malcolm Potts (standing) and Richard Helm.
Gloeocapsa
Gloeocapsa isolated from a field site on the Virginia Tech campus stained with fluorescent dyes to highlight the exterior of the extracellular matrix (green) as well as the individual cells (red). Photo courtesy of Jody Jervis and Kevin Horn (VIGEN laboratories)

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