Project description:With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared to ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSCs to model the effects of spaceflight on human cardiomyocyte structure and function.
Project description:Genomic plasticity helps adapt to extreme environmental conditions. We tested the hypothesis that exposure to space environment (ESE) impacts the epigenome as marked by DNA hypomethylation to induce genomic plasticity in responders. Murine skin samples from the Rodent Research Reference Mission-1 were procured from the International Space Station (ISS) National Lab. Targeted RNA sequencing to test differential gene expression between the skin of ESE versus ground controls revealed upregulation of VEGF mediated angiogenesis pathways secondary to promoter hypomethylation in responder ESE cohort. Methylome sequencing identified ESE-sensitive candidate hypomethylated genes including developmental angiogenic genes Araf, VegfbandVegfr1. Based on differentially expressed genes, the angiogenesis biofunction was enriched in responders compared to non-responders. The induction of genomic plasticity in response to ESE, as reported herein, may be viewed as a mark of biological resilience that is evident in a minority of organisms, responders but not in non-responders, exposed to the same stressor. Inducible genomic plasticity may be implicated in natural resilience to ESE.
Project description:Genomic plasticity helps adapt to extreme environmental conditions. We tested the hypothesis that exposure to space environment (ESE) impacts the epigenome as marked by DNA hypomethylation to induce genomic plasticity in responders. Murine skin samples from the Rodent Research Reference Mission-1 were procured from the International Space Station (ISS) National Lab. Targeted RNA sequencing to test differential gene expression between the skin of ESE versus ground controls revealed upregulation of VEGF mediated angiogenesis pathways secondary to promoter hypomethylation in responder ESE cohort. Methylome sequencing identified ESE-sensitive candidate hypomethylated genes including developmental angiogenic genes Araf, VegfbandVegfr1. Based on differentially expressed genes, the angiogenesis biofunction was enriched in responders compared to non-responders. The induction of genomic plasticity in response to ESE, as reported herein, may be viewed as a mark of biological resilience that is evident in a minority of organisms, responders but not in non-responders, exposed to the same stressor. Inducible genomic plasticity may be implicated in natural resilience to ESE.
Project description:In recent times, long-term stay has become a common occurrence in the International Space Station (ISS). However, adaptation to the space environment can sometimes pose physiological problems to the astronauts after their return. Therefore, it is important to develop healthcare technologies for astronauts. In this study, hair, an easy-to-obtain sample, was identified as the candidate. In order to investigate the genetic changes in human hair during space flight, the hair follicles of 10 astronauts were analyzed by DNA microarray and real time q-PCR analyses.
Project description:Comparitive gene expression in skin between mice maintained in microgravity (0g) and normogravity (1g) environment. Six male C57Bl/J10 mice were housed for 91 days in the specially designed \Mouse Drawer System\ in weightlessness aboard the International Space Station. Three wild-type mice (WT) and three transgenic mice overexpressing the osteogneic factor PTN/OSF1 under the control of the human bone specific ostecalcin promoter (Tg) were used in the experiment. During the 3-month stay on the ISS, 3 mice unfortunately died leaving 2 Tg and 1 WT. \MDS tissue sharing program\ allowed several teams to study various tissues from these mice. Our aim was to investigate the effect of such a long period of microgravity on skin physiology by morphological, biochemical and genomewide analyses by comparison to similar mice on ground. Gene expression in the skin of 3 space mice and of 3 ground mice was analyzed by microarray. As this unique experiment performed on 3 mice limits the power of statistical analyis, as the transgene PTN/OSF1 was not overexpressed in skin and as a pair wise Pearson's correlation rates between the individual levels of expressed transcripts in the WT and the Tg mice were not significantly different from each other in one experimental group (space or ground), data from the 3 mice were combined to compare results from the space an ground groups.
Project description:The on-going Microbial Observatory Experiments on the International Space Station (ISS) revealed the presence of various microorganisms that may be affected by the distinct environment of the ISS. The low-nutrient environment combined with enhanced irradiation and microgravity may trigger changes in the molecular suit of microorganisms leading to increased virulence and resistance of microbes. Proteomic characterization of two Aspergillus fumigatus strains, ISSFT-021 and IF1SW-F4, isolated from HEPA filter debris and cupola surface of the ISS, respectively, is presented, along with a comparison to experimentally established clinical isolates Af293 and CEA10. In-depth analysis highlights variations in the proteome of both ISS-isolated strains when compared to the clinical strains. Proteins up-regulated in ISS isolates were involved in oxidative stress response, and carbohydrate and secondary metabolism. This report provides insight into possible molecular adaptation of filamentous fungi to the unique ISS environment. Lastly, an attempt was made to elucidate plausible causes of the enhanced virulence of both ISS-isolated A. fumigatus strains.
Project description:Genome-wide transcriptional profiling shows that reducing gravity levels in the International Space Station (ISS) causes important alterations in Drosophila gene expression. However, simulation experiments on ground, without space constraints, show weaker effects than space environment. A global and integrative analysis using the “gene expression dynamics inspector” (GEDI) self-organizing maps, reveals a subtle response of the transcriptome using different populations and microgravity and hypergravity simulation devices. These results suggest that, in addition to behavioural responses that can be detected also at the gene expression level, the transcriptome is finely tuned to normal gravity. The alteration of this constant parameter on Earth can have effects on gene expression that depends both on the environmental conditions and the ground based facility used to compensate the gravity vector. Alternative and commons effects of mechanical facilities, like the Random Positioning Machine and a centrifuge, and strong magnetic field ones, like a cryogenically cooled superconductive magnet, are discussed.
Project description:In recent times, long-term stay has become a common occurrence in the International Space Station (ISS). However, adaptation to the space environment can sometimes pose physiological problems to the astronauts after their return. Therefore, it is important to develop healthcare technologies for astronauts. In this study, hair, an easy-to-obtain sample, was identified as the candidate. In order to investigate the genetic changes in human hair during space flight, the hair follicles of 10 astronauts were analyzed by DNA microarray and real time q-PCR analyses. Space environment induced gene expression of hair follicles of astronaut was measured 6 differnent times included 2 in flight on orbit. Ten independent experiments were performed on differing astronauts. and the sampling day was differed for each astronaut because of their schedules.
Project description:Larvae-Pupae transition flies (Drosophila) were recovered and transport for 3 days at 12-14ºC to arrest development until the launch site, then exposed to RT (18-20ºC) for some hours including the launch and trip to the International Space Station, then pupae were exposed to microgravity in the ISS for 4 days and a half at 22ºC. Finally pupae were fixed on acetone and frozen until recovery on Earth.<br><br><br><br>Four groups of samples: 1 ISS (+ground control) as described, 2 RPM (microgravity simulator on Earth) as described, 3 RPM without constrains (No MAMBA container and only 5 days exposure without cold transport) and 4 centrifuge 10g without constrains control..
Project description:This study presents the first global genomic, proteomic, and secondary metabolomic characterization of the filamentous fungus, Aspergillus nidulans, following growth on the International Space Station (ISS). The investigation included the A. nidulans wild-type and 3 mutant strains, two of which were genetically engineered to enhance secondary metabolite (SM) production. Whole genome sequencing (WGS) revealed that ISS conditions altered the A. nidulans genome in specific regions. In strain CW12001, which features overexpression of the SM global regulator laeA, ISS conditions induced a point mutation that resulted in the loss of the laeA stop codon. Differential expression of proteins involved in stress response, carbohydrate metabolic processes, and SM biosynthesis was observed. ISS conditions significantly decreased prenyl xanthone production in the wild-type strain and increased asperthecin production in LO1362 and CW12001, which are deficient in a major DNA repair mechanism. Together, these data provide valuable insights into the genetic and molecular adaptation mechanism of A. nidulans to the spacecraft environment and present many economic benefits.