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Understanding the effects of microgravity on human organs is crucial to exploration of low-Earth orbit, the Moon, and beyond. Drosophila can be sent to space in large numbers to examine the effects of microgravity on heart structure and function, which is fundamentally conserved from flies to humans. Flies reared in microgravity exhibit reduced climbing ability, cardiac constriction with myofibrillar remodeling, and diminished cardiac output. Analysis of gene expression in isolated hearts revealed reduced expression of sarcomeric / extracellular matrix (ECM) genes and increased expression of genes encoding proteasome subunits (cellular garbage disposals). We further examined the role of proteasomes and protein misfolding on a second flight. We sent flies expressing fluorescently labeled proteins that we could monitor when returned to Earth for misfolding (as protein plaques). We were also able to use staining techniques to monitor proteasome numbers. We observed dramatic increases in protein plaque number and size in flies exposed to micro g and these were co-localized with large proteasome aggregates. Remarkably, in long-QT causing seizure (sei) / human ether-a-go-go (hERG) mutants, proteasomal gene expression was already lower than wildtype at 1g , but under micro g we still observed an increase compared to the 1g ground controls. Therefore, cardiac remodeling and proteostatic stress may be a fundamental response of heart muscle to microgravity. Our experiments validated the use of Vented Fly Boxes (VFBs) for fly experiments that require minimal space and astronaut input yet provide significant insights into organismal function under low gravity. One unexpected outcome from our second flight was excessive fungal contamination of samples stored in the Space Automated Bioproduct Lab (SABL) incubator. This information should assist future experiments that use this equipment to ensure that the experiments are not compromised by external contaminants. Nevertheless, the inclusion of fly boxes that were maintained as backup for the original flight permitted us to complete our analyses. The complete gene expression dataset is available on NASA's GeneLab database. Although not part of our original proposal we also developed an assay to measure both gene and protein expression from the same tissue source (brain) from the flies. Our analyses suggest that there are fundamental changes in proteins in metabolic pathways, circadian rhythm signaling, and the visual system that occur in micro g. This dataset is also available on GeneLab.
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Articles in Peer-reviewed Journals
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Walls S, Diop S, Birse R, Elmen L, Gan Z, Kalvakuri S, Pineda S, Reddy C, Taylor E, Trinh B, Vogler G, Zarndt R, McCulloch A, Lee P, Bhattacharya S, Bodmer R, Ocorr K. "Prolonged exposure to microgravity reduces cardiac contractility and initiates remodeling in Drosophila." Cell Rep. 2020 Dec 8;33(10):108445. ePub 2020.
https://doi.org/10.1016/j.celrep.2020.108445 ; PubMed PMID: 33242407; PubMed Central PMCID: PMC7787258 , Dec-2020
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Articles in Peer-reviewed Journals
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Gilbert R, Torres ML, Clemens R, Hateley S, Hosamani R, Wade W, Bhattacharya S. "Spaceflight and simulated microgravity conditions increase virulence of Serratia marcescens in the Drosophila melanogaster infection model." npj Microgravity. 2020 Feb 4;6(1):4. https://doi.org/10.1038/s41526-019-0091-2 ; PubMed PMID: 32047838; PubMed Central PMCID: PMC7000411 , Feb-2020
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Articles in Peer-reviewed Journals
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Tahimic CGT, Paul AM, Schreurs AS, Torres SM, Rubinstein L, Steczina S, Lowe M, Bhattacharya S, Alwood JS, Ronca AE, Globus RK. "Influence of social isolation during prolonged simulated weightlessness by hindlimb unloading." Front Physiol. 2019 Sep 13;10:1147. https://doi.org/10.3389/fphys.2019.01147 ; PubMed PMID: 31572207; PubMed Central PMCID: PMC6753329 , Sep-2019
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Articles in Peer-reviewed Journals
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Iyer J, Mhatre SD, Gilbert R, Bhattacharya S. "Multi-system responses to altered gravity and spaceflight: Insights from Drosophila melanogaster." Neurosci Biobehav Rev. 2022 Nov;142:104880. https://doi.org/10.1016/j.neubiorev.2022.104880 ; PMID: 36126744 , Nov-2022
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NASA Technical Documents
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Ocorr K, Bodmer R, Battacharya S, Diop SB, James B, Rosa Campos A. "Correlated gene and protein expression in heads from Drosophila reared in microgravity." NASA GeneLab Data Systems/GLDS-207. , Nov-2018
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NASA Technical Documents
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Ocorr K, Diop S, Gan Z, Bodmer R. "HEART FLIES - effect of microgravity on heart function in Drosophila." NASA GeneLab Data Systems/GLDS-347. , Dec-2020
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