International Caenorhabditis elegans Experiment First Flight-Genomics (ICE-First-Genomics) investigates the whole-genome microarray analysis of responses to spaceflight in C. elegans. C. elegans (nematode worms) are relatively simple organisms that are used as a model for a wide variety of biological processes. The ICE-First investigation is a collaborative effort conducted by scientists from several countries which have the opportunity to work as a team to design related experiments that would produce valuable results for scientists across multiple disciplines.Principal Investigator(s)
NASA Ames Research Center, Moffett Field, CA, United States
National Aeronautics and Space Administration (NASA)Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)Research Benefits
Information PendingISS Expedition Duration
October 2003 - April 2004Expeditions Assigned
8Previous ISS Missions
The precursor to ICE-First (flown during Expedition 8), BRIC-60/C. elegans, flew on STS-107 (Columbia). Following the break-up of Columbia upon re-entry into the Earth's atmosphere, the samples were located among debris in East Texas and returned to NASA.
ICE-First-Genomics is one of several experiments that investigate the effects of spaceflight on a model organism of the nematode worm family (Caenorhabditis elegans) and aims to develop links to human physiology in space. The organism chosen for this study is known to be able to mate, reproduce and develop apparently normally during space flight. Spaceflight 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 (to reduce pressure). C. elegans is a round worm or nematode (Phylum Nematoda) measuring around 1mm and is found naturally in soil. Its body is composed of 959 cells and includes complete reproductive, nervous, muscular, and digestive systems. C. elegans are hermaphrodites (displaying two genders and possessing the ability of self fertilization). Its life span is about 2-3 weeks; although, concerning the liquid medium used for this study at 25°, the life cycle is around 5 days. The entire genome has been sequenced and consists of 97 million base pairs (compared to the 3,000 million found in the human genome) and around 20,000 genes (compared to the 30,000 that humans have) and an entire library of well characterized mutants are available. C. elegans has been used as a model system for various medical pathologies and was the subject of the 2002 Nobel Prize in Medicine or Physiology because the process of programmed cell death or apoptosis was first discovered while studying C. elegans development. A number of additional physiological phenomena have been reported, such as immune dysfunction and altered aging that are not well understood at the cellular or molecular level. Microarray analysis is an excellent method of screening for both known and novel genes that show altered expression in response to a particular treatment. The ICE-First-Genomics experiment involves performing RNA expression analysis using a microarray designed to probe for nearly every gene in the genome. Two hypotheses that can be tested directly using microarray data obtained from space flown worms are a) that radiation-repair genes are unregulated, and b) that genes involved in muscle specification and contractility are down-regulated. The analysis does not provide information concerning the specific role of any of these genes, but does confirm that genes predicted to show altered expression based on data from mammals are indeed responsive in worms. Additional hypotheses concerning worm ?immune? function and aging can also be tested by determining the expression of genes known to be involved in those physiological processes. These results would provide excellent preliminary data for proposing follow-up spaceflight experiments to examine specific genes in detail. Whole-genome analyses provide a useful resource to the entire scientific community, as any researcher considering a particular line of study can check microarray data to determine whether their genes of interest respond to treatment.
The possibilities for longer-term spaceflights are increasing. These types of experiments give scientists an insight into the effect that the environment of space will have on organisms down to the genetic level.Earth Applications
With certain genetic techniques used in this experiment, highlighting the genes where differences occur in comparison to Earth data can further provide scientists with a direction of where to develop research in the future, either on similar organisms or humans. By understanding fundamental processes in C. elegans, scientists can better understand the human counterparts. This study can lead to a further understanding of muscle function and development.
ICE-First-Genomics samples are placed in either the Kubik Topaz or Kubik Amber incubator before and after the launch. This experiment requires the samples for RNA analysis to be frozen within 1 to 2 hours prior the return to Earth. RNA will be analyzed using the whole-genome microarray developed by a lab located at the Stanford Genome Center in Stanford, California. Data from the microarray analysis will be made publicly available in the Stanford Microarray Database. The worms will be prepared from a CC1 mixed stage population, kept at 18°C until the launch and following the launch, whereby they will be recovered alive for immediate treatment. Filming is required immediately upon the arrival on Earth for later evaluation.Operational Protocols
The C. elegans samples are transported to the launch pad in Baikonur, transferred into the Kubik Topaz (incubator with microgravity plate) and kept at 18 degrees C. Three days after the launch, 3 samples are transferred into the Kubik Amber (incubator with centrifuge), while the other five samples remain in Kubik Topaz. On the last flight day, four of the C. elegans samples are injected with a fixative by the crew and all of the samples are placed in Kubik Topaz on the Soyuz and returned to Earth. Upon return to Earth, the containers are filmed to evaluate the behavior of the C. elegans following space flight. The small bags containing the culture of the worms are either frozen or refrigerated until they are returned to their respective principal investigators for detailed analysis.
There are three themes that emerged from the ICE-First-Genomics microarray data. First, there are few genes that show reproducible changes in response to spaceflight when assayed in multiple replicates of a population. This may mean that gene responses to spaceflight are small and/or that the number of genes altered in response to spaceflight is relatively small. Second, there are some genes that show reproducible changes in response to spaceflight both within replicates of a population and across populations. Notably, the genes that have these highly reproducible changes are largely metabolic (decreased) and stress response genes (increased). Additionally, the bulk of these genes are thought to be regulated by two signaling pathways that the worm uses to sense and respond to the external environment, Insulin and TGF-beta. Third, within the class of genes that gave reproducible changes in expression, it is possible to identify genes that change in only two of three populations during spaceflight; for example, decreased expression of neuromuscular genes. This may suggest differential sensitivity of populations to spaceflight, or population differences in exposure to multiple vs. individual stressors associated with spaceflight. This may also explain why one population of space flown worms had a post-flight movement defect while one did not, and also why there is wide variability in muscle loss in astronauts and cosmonauts. Together, these results paint a semi-convincing picture of how C. elegans modulate gene expression in response to spaceflight.
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