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Microarray-Bound Worm Experiment Heads for International Space Station

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A clutch of three million Caenorhabditis elegans worms joined the three astronauts who blasted off from Russia’s Baikonur Cosmodrome in Kazakhstan on Monday, on their way to a rendezvous with the International Space Station, which is orbiting some 240 miles above Earth.

The worms will be exposed to space conditions as part of a series of experiments that will include one package destined for microarray analysis to be conducted back on Earth in the laboratory of Stuart Kim, a professor of developmental biology at Stanford University, in conjunction with Catharine Conley, a researcher with the Life Sciences Division at NASA-Ames Research Center.

The microarray experiment, “Whole-genome microarray analysis of responses to space flight in C. elegans,” will analyze the genome of C. elegans to test for changes in gene expression related to space conditions. In particular, the experiment will focus on possible changes in expression of genes involved in muscle contraction or radiation-damage repair.

The experiment is an early-stage discovery effort that will help scientists learn how to prepare the worms for live space flight and how to conduct analysis on them when the flight is completed. There will not be any glass slides, GeneChips, reagents or scanners onboard the ISS. In fact, Kim, who runs Stanford’s C. elegans microarray center, told BioArray News that the labor-atory would close in June.

“Doing a microarray is no big deal right now, and there is no need to continue to have a centralized facility,” he said.

Still, the lab will conduct the analysis for Conley using its Pat Brown/Joe DiRisi-designed spotting robot and spotted cDNA slides, which contain probes to about 94 percent of the genes of C. elegans, and use 1-kilobase probes from an exon-rich part of the genome, Kim told BioArray News.

So, while microarrays have almost reached such commodity status on Earth that facilities like Kim’s C. elegans microarray core lab at Stanford have become redundant enough to close, the technology is still not miniaturized and self-contained enough for easy use in environmentally extreme locations like space, requiring efforts like the measures used to get these worms to the space station so that eventually their genomes can be profiled.

European Space Agency astronaut André Kuipers of the Netherlands is overseeing the worms as part a package of life sciences experiments in his nine-day mission. He joined Lt. Col. Edward Mike Fincke of the US Air Force, and Col. Gennadi Padalka of the Russian Air Force in the capsule of a Soyuz rocket Monday to start the two-day trip to rendezvous with the space station.

Fincke and Padalka are replacing Michael Foale and Alexander Kaleri, the current crew of the space station, and will remain onboard the vessel for a six-month tour while Kuipers, only the second Dutch astronaut ever, will return to earth with Foale and Kaleri on April 29. Kuipers, who has other flight duties, will spend part of his mission conducting 21 science experiments that are part of the estimated €15 million DELTA (Dutch Expedition for Life Science, Technology and Atmospheric Research) mission.

This mission marks a milestone for the space station, which has been in transition since the February 2003 crash of the US space shuttle Columbia, which halted US space shuttle efforts as the disaster was investigated, leaving the Russian rockets as the only means to access and supply the 16-country sponsored space station.

Microarray Experiment

The experiment is spelled out in more detail on the website of the Netherlands organization coordinating the experiments. According to the organization’s website [http://www.desc.med.vu.nl/Frames.htm] two hypotheses will be tested using the microarray-based data obtained from the space-flown worms: (1) that radiation-repair genes will be up-regulated; and (2) that genes involved in muscle specification and contractility will be down-regulated.

“Space flight is suspected or has been recognized to produce specific physiological responses, including radiation damage repair in response to cosmic radiation, and muscle atrophy in response to microgravity-induced unweighting,” the website [http://www.desc.med.vu.nl/NL-taxi/ICE/ICE-page1.htm] says. “A number of additional physiological phenomena have been reported, such as immune dysfunction and altered aging, which are not well understood at the cellular or molecular level.”

The worms will return to Earth alive and samples for RNA analysis will be created within one or two hours after the spacecraft has been recovered. The RNA will be analyzed using the whole-genome microarray developed by the Kim lab in the Stanford Genome Center. Data from the microarray analysis will be made publicly available in the Stanford Microarray Database.

The worms will fly in a liquid medium provided by NASA. The various strains of worms will be prepared in the laboratory of the investigators for use in the space mission. Four days before the launch, the worms were prepared for the flight by the investigators in the facility of the GSBMS (Groupement Scientifique pour la Biologie et la Médecine Spaciale) in Toulouse, France, and then put in their containers, ready for the ground and space travel to follow.

They were transported by courier to the launch pad in Baikonour. Then, three days after the launch, the samples were to transfer to the Kubik, an environmentally controlled package, which holds a centrifuge and three containers of worms. On the last day of the flight, the containers will be fixed by the astronaut to return to the ground in the Soyuz.

On arrival the containers will be opened and some will be filmed to evaluate the behavior of the animals. The bags containing the worms will be then either frozen or refrigerated till their return in Toulouse two days after the landing. The scientists will then begin their scientific work.

For Kim of Stanford, this experiment only provides a taste of what could be learned when microarray-type technology can actually go up in space.

“When you look at the type of experiments that have gone up in the space shuttle, there are all sorts of testing to see if something is different in space,” he said. “There is a lot of if, if, if, but you don’t know. Instead of doing this if, if, if stuff, why don’t we let the genome report back. We just send up the ‘canary’ into the space coal mine and let the genome respond to it. We could capture that by RNA profile, and take it back to Earth and deconvolute it. That’s the real experiment. If you could have that, you could deconvolute a very complex profile, and you could make great hypotheses to test.”

Still, when it comes to model species for space experimentation, C. elegans is a veteran. The little critter has already shown that it can mate, reproduce, and develop apparently normally during space flight.

And, after the crash of Columbia, five canisters of the worms for experiments that Kim had helped design were found, with the worms still alive, in the debris field from the ill-fated orbiter.

“That proved that this is a hearty space animal,” Kim said.

So, while NASA reinvents itself in the wake of the Columbia disaster, there are those who see a bright future for this research in space.

“Irrespective of the directions biological research will take in the ‘new NASA’ there is likely to be a place for gene-expression analysis,”said Paul Todd, chief scientist for Space Hardware Optimization Technology (SHOT) of Greenville, Ind., a NASA partner company that creates systems for space flight experimentation, and provides support services.

—MOK

 

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