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IN DEPTH: Genomics Studies in Space May Offer More Than Just Gee Whiz Science

Washington, DC, July 25 - With an eye toward understanding how human life behaves in space--as well as here on Earth--NASA has awarded genomics researchers several grants to perform gene expression studies, part of a $27 million, 43 project biotechnology in space initiative announced last month.

Genomics in space might initially sound far-fetched, but researchers connected with the project say experiments conducted in microgravity can sometimes more closely approximate in vivo conditions, and may also provide important data about how the human body can survive prolonged periods of weightlessness.

Gene expression is a particularly fertile area for microgravity research, because the laboratory cell cultures used in experiments on earth tend to settle to the bottom of their petri dishes. When this happens, the piled up layers of cells don't function as they would in a three-dimensional tissue or organ because changes in the cytoplasmic structure--the cell's skeleton--also affect gene expression in the nucleus. "The cell knows there's a dish, attaches to the dish, and the gene expression changes," said Tom Misteli, a cell biologist familiar with the NASA work who leads a group studying the cell biology of gene expression at the National Cancer Institute.

Initially, NASA tried to solve this problem by simulating microgravity on Earth using a rotating vessel called the Bioreactor. The rotating vessel keeps the cells in suspension, preventing them from settling to the bottom. This works well for small groups of cells, but as the cultures grow larger, the Bioreactor must spin faster in order to counteract their weight. At this point, shear forces and collisions between the cells merely replace one source of cell damage with another. 

Performing these experiments in space, however, should eliminate these gravitational and rotational forces, as well as open new frontiers for understanding biology. "I think there's boundless potential" for genomics research in the microgravity environment of the International Space Station, said J. Milburn Jessup, a cancer researcher at the University of Texas and chair of the Space Station Utilization Advisory Committee. "I expect we'll be able to create novel tissues and study gene expression in three-dimensional arrays."

In fact, astronauts on the space station will carry out one of Jessup's experiments in August, as part of a package of gene expression studies. His experiment, a study of colorectal cancer and the genes associated with its invasiveness and potential to form metastases, is important for determining a patient's treatment options, he said. 

Another experiment in the package will investigate gene expression in kidney cells, by comparing the pattern in the three-dimensional cultures achieved in spaceflight to the cultures seen in ground-based laboratories. The comparison will help scientists learn about control genes responsible for differentiation and tissue formation, said Timothy Hammond, a kidney researcher at Tulane University who designed the experiment. 

Histeli, the NCI researcher, agreed that the microgravity experiments have the potential to bring back valuable data. "[It's] quite pioneering," he said. "We know a lot about the biochemistry of gene expression, but few [scientists] are looking at how genes are actually expressed in living cells."

However, although the proposed experiments have significant scientific potential, completing them may not be easy. One of the challenges of doing research on the orbiting outpost, Jessup said, is that the experiments may not be returned to Earth until months after they are performed. Researchers would like to find a way to process the samples on board, but cost overruns during construction of the space station resulted in cutbacks limiting the size of the crew that can be accommodated. 

"We'd love to be able to freeze the samples," Jessup said, but until November the only cold storage available on board is a refrigerator. Still, ground-based experiments indicate that samples kept in a refrigerator at four degrees Celsius for several months will yield just enough RNA to study gene expression, he said.

Ultimately, Hammond said, the goal of the space station work is to apply the knowledge of cellular machinery gained in space to making experiments on Earth easier and more productive. "We may use the knowledge from space and figure out how to do the same thing in a much simpler way," he said. 

"That's what it's all about, helping people on the ground," he added. "That's what justifies the money that's being spent."

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