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Project Title:  The Effects of Microgravity on Cardiac Function, Structure and Gene Expression using the Drosophila Model Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Invertebrate  
Start Date: 09/01/2013  
End Date: 09/30/2020  
Task Last Updated: 09/22/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bodmer, Rolf  Ph.D. / Sanford-Burnham Medical Research Institute 
Address:  Development & Aging 
10901 N Torrey Pines Rd 
La Jolla , CA 92037-1005 
Email: rolf@sbpdiscovery.org 
Phone: 858-795-5295  
Congressional District: 49 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Sanford-Burnham Medical Research Institute 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bhattacharya, Sharmila  Ph.D. NASA Ames Research Center 
Ocorr, Karen  Ph.D. Burnham Institute for Medical Research 
Project Information: Grant/Contract No. NNX13AN38G 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Yuri.V.Griko@nasa.gov 
Unique ID: 9354 
Solicitation / Funding Source: 2012 Space Biology NNH12ZTT001N 
Grant/Contract No.: NNX13AN38G 
Project Type: FLIGHT 
Flight Program: ISS 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Invertebrate
Space Biology Cross-Element Discipline: (1) Reproductive Biology
(2) Developmental Biology
(3) Musculoskeletal Biology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: ISS

NOTE: Extended to 9/30/2020 per NSSC information (Ed., 9/25/19)

NOTE: Extended to 9/30/2019 per F. Hernandez/ARC; previously had been extended to 9/30/2018 (Ed. 9/21/18)

NOTE: Extended to 9/30/2018 per F. Hernandez/ARC (Ed., 4/13/18)

NOTE: Extended to 6/30/2018 per NSSC information (Ed., 10/10/17)

NOTE: Extended to 9/30/2017 per NSSC information (Ed., 7/18/16)

NOTE: Extended to 12/31/2015 per NSSC information (Ed., 2/18/16)

NOTE: Extended to 10/31/2015 per NSSC information (Ed., 9/15/15)

Task Description: The detrimental effects of spaceflight on the cardiovascular system are well known. It is believed that these effects may lead to clinically significant risks to astronauts on long duration space missions as well as to the success of these missions themselves. Current studies are limited primarily to human studies and rodent experiments. However, these model systems and human studies have significant limitations that may be addressed by using the well-established Drosophila model. Drosophila have previously been successfully launched into space and a ground-based Drosophila model for cardiac disease and function has been developed. However, the genetically versatile Drosophila model has yet to be used for studying the effects of spaceflight on the cardiovascular system.

We flew 4 genotypes of Drosophila aboard the International Space Station (ISS) for approximately 30 days, along with identical 1-g ground controls. The Drosophila required minimal astronaut intervention, primarily transfer to an incubator and stowage within the ISS. The samples will be retrieved post-flight and analyzed using established methods. Heart function, including measurements of diastolic and systolic intervals, heart rate, heart diameters, contractility, and arrhythmias was recorded. Microscopic and immuno-histochemical evaluations of heart morphology was carried out. Messenger RNA (mRNA) expression by RNA Sequencing (RNA Seq) was conducted on both heart and brain tissue.

The ultimate goal of this research was to obtain data on heart muscle function in low gravity while validating the Drosophila model for studying the effects of spaceflight on cardiac disease and function. Our studies identified disruption in metabolic gene expression and a dramatic increase in proteasome gene expression. This was confirmed in a subsequent flight with immuno-histochemical analyses. The increased proteasome numbers correlated with an increase in amyloid-like protein aggregations within the heart tissue and with increased myofibrillar disarray. We also documented a decrease in collagen fibers associated with the sarcomere Z-lines within myocardial cells.

Research Impact/Earth Benefits: Information about cardiac muscle function in microgravity is expected to provide insights on genetic and molecular changes that occur with muscle atrophy on Earth. For example, we identified an increase in misfolded muscle protein associated with aggregated proteasomes in the heart muscle cells. Similar alterations in protein processing may underlie the muscle atrophy that occurs during prolonged bed rest or muscle disuse in muscular dystrophies.

Task Progress & Bibliography Information FY2020 
Task Progress: 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.

Bibliography: Description: (Last Updated: 06/23/2023) 

Show Cumulative Bibliography
 
Articles in Peer-reviewed Journals 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
Articles in Peer-reviewed Journals 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
Articles in Peer-reviewed Journals 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
Articles in Peer-reviewed Journals 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
NASA Technical Documents 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
NASA Technical Documents 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
Project Title:  The Effects of Microgravity on Cardiac Function, Structure and Gene Expression using the Drosophila Model Reduce
Images: icon  Fiscal Year: FY 2018 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Invertebrate  
Start Date: 09/01/2013  
End Date: 09/30/2020  
Task Last Updated: 06/17/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bodmer, Rolf  Ph.D. / Sanford-Burnham Medical Research Institute 
Address:  Development & Aging 
10901 N Torrey Pines Rd 
La Jolla , CA 92037-1005 
Email: rolf@sbpdiscovery.org 
Phone: 858-795-5295  
Congressional District: 49 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Sanford-Burnham Medical Research Institute 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bhattacharya, Sharmila  Ph.D. NASA Ames Research Center 
Ocorr, Karen  Ph.D. Burnham Institute for Medical Research 
Project Information: Grant/Contract No. NNX13AN38G 
Responsible Center: NASA ARC 
Grant Monitor: Sato, Kevin  
Center Contact: 650-604-1104 
kevin.y.sato@nasa.gov 
Unique ID: 9354 
Solicitation / Funding Source: 2012 Space Biology NNH12ZTT001N 
Grant/Contract No.: NNX13AN38G 
Project Type: FLIGHT 
Flight Program: ISS 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Invertebrate
Space Biology Cross-Element Discipline: (1) Reproductive Biology
(2) Developmental Biology
(3) Musculoskeletal Biology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: ISS

NOTE: Extended to 9/30/2020 per NSSC information (Ed., 9/25/19)

NOTE: Extended to 9/30/2019 per F. Hernandez/ARC; previously had been extended to 9/30/2018 (Ed. 9/21/18)

NOTE: Extended to 9/30/2018 per F. Hernandez/ARC (Ed., 4/13/18)

NOTE: Extended to 6/30/2018 per NSSC information (Ed., 10/10/17)

NOTE: Extended to 9/30/2017 per NSSC information (Ed., 7/18/16)

NOTE: Extended to 12/31/2015 per NSSC information (Ed., 2/18/16)

NOTE: Extended to 10/31/2015 per NSSC information (Ed., 9/15/15)

Task Description: The detrimental effects of spaceflight on the cardiovascular system are well known. It is believed that these effects may lead to clinically significant risks to astronauts on long duration space missions as well as to the success of these missions themselves. Current studies are limited primarily to human studies and rodent experiments. However, these model systems and human studies have significant limitations that may be addressed by using the well-established Drosophila model. Drosophila have previously been successfully launched into space and a ground-based Drosophila model for cardiac disease and function has been developed. However, the genetically versatile Drosophila model has yet to be used for studying the effects of spaceflight on the cardiovascular system. We are currently preparing flies for a scheduled launch in Sept. 2015 and analyzing data from a preliminary space flown test of our experimental system.

In this proposal we propose to fly groups of Drosophila aboard the International Space Station (ISS) for approximately 30 days, along with identical on-board 1-g controls as well as ground controls. The Drosophila will require minimal astronaut intervention involving changing feeding trays on 1 or 2 occasions. The samples will be retrieved post-flight and analyzed using established methods. Heart function, including measurements of diastolic and systolic intervals, heart rate, heart diameters, contractility, and arrhythmias will be recorded. Microscopic and immunohistochemical evaluations of heart morphology will also be carried out. We will also conduct intracellular membrane potential recordings of the heart. Finally, we will analyze mRNA expression with a microarray.

The ultimate goal of this research is to obtain data while validating the Drosophila model for studying the effects of spaceflight on cardiac disease and function. The development of such a model would be a potentially significant advancement in the study and understanding of how spaceflight affects the cardiovascular system, and may ultimately lead to countermeasures to prevent them.

Research Impact/Earth Benefits: Information about cardiac muscle function in microgravity is also expected to provide insights on genetic and molecular changes that occur with muscle atrophy on Earth. For example, we expect to identify basic molecular alterations that are associated with muscle atrophy that occurs during prolonged bed rest or muscle disuse in muscular dystrophies.

Task Progress & Bibliography Information FY2018 
Task Progress: [Ed. note (June 2019)--compiled from PI's technical progess report covering work done through August 2018]

We have finished out functional assessments of Canton S and sei/hERG mutant hearts. Our data confirm a small but significant reduction in heart size of the wildtype space flown flies. They also have disorganized myofibrils (phalloidin stained F-actin, green) and reduced cardiac extracellular skeleton (pericardin/CollagenIV, red). Hearts from space flown sei/hERG mutant flies are also smaller than mutant ground controls and show even more disorganized myofiblils and in particular drastically reduced cardiac extracellular skeleton. We also see significant reductions in the extracellular matrix from other fly lines that we flew. We are currently writing up the data on the Canton S and sei/HERG flies and have begun assessing the data for the w/ KCNQ flies from the latest mission.

Analysis of transcriptome (fly hearts and heads) and proteasome (fly heads – gene lab) is currently in progress. We have spent the past 6 months processing neuronal material (heads) from flies. We have established a relatively new capability that allows us to isolate both RNA and protein from the same samples. We have successfully applied this protocol to tissue from Heart Flies and have now uploaded both sets of data to GeneLab servers. It is our intention to ultimately apply this technology to samples from this mission.

Bibliography: Description: (Last Updated: 06/23/2023) 

Show Cumulative Bibliography
 
 None in FY 2018
Project Title:  The Effects of Microgravity on Cardiac Function, Structure and Gene Expression using the Drosophila Model Reduce
Images: icon  Fiscal Year: FY 2017 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Invertebrate  
Start Date: 09/01/2013  
End Date: 09/30/2019  
Task Last Updated: 05/20/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bodmer, Rolf  Ph.D. / Sanford-Burnham Medical Research Institute 
Address:  Development & Aging 
10901 N Torrey Pines Rd 
La Jolla , CA 92037-1005 
Email: rolf@sbpdiscovery.org 
Phone: 858-795-5295  
Congressional District: 49 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Sanford-Burnham Medical Research Institute 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bhattacharya, Sharmila  Ph.D. NASA Ames Research Center 
Ocorr, Karen  Ph.D. Burnham Institute for Medical Research 
Project Information: Grant/Contract No. NNX13AN38G 
Responsible Center: NASA ARC 
Grant Monitor:  
Center Contact:   
Unique ID: 9354 
Solicitation / Funding Source: 2012 Space Biology NNH12ZTT001N 
Grant/Contract No.: NNX13AN38G 
Project Type: FLIGHT 
Flight Program: ISS 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Invertebrate
Space Biology Cross-Element Discipline: (1) Reproductive Biology
(2) Developmental Biology
(3) Musculoskeletal Biology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: ISS

NOTE: Extended to 9/30/2019 per F. Hernandez/ARC; previously had been extended to 9/30/2018 (Ed. 9/21/18)

NOTE: Extended to 9/30/2018 per F. Hernandez/ARC (Ed., 4/13/18)

NOTE: Extended to 6/30/2018 per NSSC information (Ed., 10/10/17)

NOTE: Extended to 9/30/2017 per NSSC information (Ed., 7/18/16)

NOTE: Extended to 12/31/2015 per NSSC information (Ed., 2/18/16)

NOTE: Extended to 10/31/2015 per NSSC information (Ed., 9/15/15)

Task Description: The detrimental effects of spaceflight on the cardiovascular system are well known. It is believed that these effects may lead to clinically significant risks to astronauts on long duration space missions as well as to the success of these missions themselves. Current studies are limited primarily to human studies and rodent experiments. However, these model systems and human studies have significant limitations that may be addressed by using the well-established Drosophila model. Drosophila have previously been successfully launched into space and a ground-based Drosophila model for cardiac disease and function has been developed. However, the genetically versatile Drosophila model has yet to be used for studying the effects of spaceflight on the cardiovascular system. We are currently preparing flies for a scheduled launch in Sept. 2015 and analyzing data from a preliminary space flown test of our experimental system.

In this proposal we propose to fly groups of Drosophila aboard the International Space Station (ISS) for approximately 30 days, along with identical on-board 1-g controls as well as ground controls. The Drosophila will require minimal astronaut intervention involving changing feeding trays on 1 or 2 occasions. The samples will be retrieved post-flight and analyzed using established methods. Heart function, including measurements of diastolic and systolic intervals, heart rate, heart diameters, contractility, and arrhythmias will be recorded. Microscopic and immunohistochemical evaluations of heart morphology will also be carried out. We will also conduct intracellular membrane potential recordings of the heart. Finally, we will analyze mRNA expression with a microarray.

The ultimate goal of this research is to obtain data while validating the Drosophila model for studying the effects of spaceflight on cardiac disease and function. The development of such a model would be a potentially significant advancement in the study and understanding of how spaceflight affects the cardiovascular system, and may ultimately lead to countermeasures to prevent them.

Research Impact/Earth Benefits: Information about cardiac muscle function in microgravity is also expected to provide insights on genetic and molecular changes that occur with muscle atrophy on Earth. For example, we expect to identify basic molecular alterations that are associated with muscle atrophy that occurs during prolonged bed rest or muscle disuse in muscular dystrophies.

Task Progress & Bibliography Information FY2017 
Task Progress: [Ed. note (March 2019)--compiled from PI's technical progress report covering work done through October 2017]

A total of 8 Vented Fly Boxes (VFBs) were received from NASA-Ames personnel on July 4, 2017. These included VFB001–VFB006 that had been flown to the International Space Station (ISS) on June 3, 2017 aboard SpaceX CRS-11 and returned to Long Beach Port on July 4, 2017. In addition, we received two VFBs with the synchronous ground controls, which we designated VFB007 (adult sample) and 008 (egg lay sample). The VFBs were opened and photos of all vials and VFBs were obtained. All space flown samples returned with varying amounts of visible fungal contamination. As a result of the fungal contamination we chose to use minimal numbers of these flies from the egg lay samples for our studies. Consequently we significantly revamped our workflow to harvest almost all the samples we needed from primarily the two Adult Fly VFBs.

Preliminary assessment shows that there were sufficient samples collected from the space flown flies to conduct most of the science assays listed in the original science proposal, and definitely all the critical assays. It should be noted that because we could not use the flies from VFBs stored in the Space Automated Bioproduct Laboratory (SABL) in the intended fashion, we did not achieve the optimal age grouping that was desirable for our heart function assays. In addition, we did not receive enough adult flies to follow any of these returning adults fo recovery after a week (one of the experiments outlined in our proposal). However, we were able to recover ISS born embyos and larvae from the VFBs stored in SABL that were later analyzed after reaching 2-3 weeks of adulthood. We are currently awaiting receipt of the asynchronous ground controls.

Bibliography: Description: (Last Updated: 06/23/2023) 

Show Cumulative Bibliography
 
Articles in Peer-reviewed Journals Hateley S, Hosamani R, Bhardwaj SR, Pachter L, Bhattacharya S. "Transcriptomic response of Drosophila melanogaster pupae developed in hypergravity." Genomics. 2016 Oct;108(3-4):158-67. Epub 2016 Sep 10. https://doi.org/10.1016/j.ygeno.2016.09.002 ; PubMed PMID: 27621057 , Oct-2016
Articles in Peer-reviewed Journals Hosamani R, Leib R, Bhardwaj SR, Adams CM, Bhattacharya S. "Elucidating the 'gravome': Quantitative proteomic profiling of the response to chronic hypergravity in Drosophila." J Proteome Res. 2016 Dec 2;15(12):4165-75. Epub 2016 Oct 10. https://doi.org/10.1021/acs.jproteome.6b00030 ; PubMed PMID: 27648494 , Dec-2016
Project Title:  The Effects of Microgravity on Cardiac Function, Structure and Gene Expression using the Drosophila Model Reduce
Images: icon  Fiscal Year: FY 2016 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Invertebrate  
Start Date: 09/01/2013  
End Date: 09/30/2019  
Task Last Updated: 07/29/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bodmer, Rolf  Ph.D. / Sanford-Burnham Medical Research Institute 
Address:  Development & Aging 
10901 N Torrey Pines Rd 
La Jolla , CA 92037-1005 
Email: rolf@sbpdiscovery.org 
Phone: 858-795-5295  
Congressional District: 49 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Sanford-Burnham Medical Research Institute 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bhattacharya, Sharmila  Ph.D. NASA Ames Research Center 
Ocorr, Karen  Ph.D. Burnham Institute for Medical Research 
Project Information: Grant/Contract No. NNX13AN38G 
Responsible Center: NASA ARC 
Grant Monitor: Sato, Kevin  
Center Contact: 650-604-1104 
kevin.y.sato@nasa.gov 
Unique ID: 9354 
Solicitation / Funding Source: 2012 Space Biology NNH12ZTT001N 
Grant/Contract No.: NNX13AN38G 
Project Type: FLIGHT 
Flight Program: ISS 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Invertebrate
Space Biology Cross-Element Discipline: (1) Reproductive Biology
(2) Developmental Biology
(3) Musculoskeletal Biology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: ISS

NOTE: Extended to 9/30/2019 per F. Hernandez/ARC; previously had been extended to 9/30/2018 (Ed. 9/21/18)

NOTE: Extended to 9/30/2018 per F. Hernandez/ARC (Ed., 4/13/18)

NOTE: Extended to 6/30/2018 per NSSC information (Ed., 10/10/17)

NOTE: Extended to 9/30/2017 per NSSC information (Ed., 7/18/16)

NOTE: Extended to 12/31/2015 per NSSC information (Ed., 2/18/16)

NOTE: Extended to 10/31/2015 per NSSC information (Ed., 9/15/15)

Task Description: The detrimental effects of spaceflight on the cardiovascular system are well known. It is believed that these effects may lead to clinically significant risks to astronauts on long duration space missions as well as to the success of these missions themselves. Current studies are limited primarily to human studies and rodent experiments. However, these model systems and human studies have significant limitations that may be addressed by using the well-established Drosophila model. Drosophila have previously been successfully launched into space and a ground-based Drosophila model for cardiac disease and function has been developed. However, the genetically versatile Drosophila model has yet to be used for studying the effects of spaceflight on the cardiovascular system. We are currently preparing flies for a scheduled launch in Sept. 2015 and analyzing data from a preliminary space flown test of our experimental system.

In this proposal we propose to fly groups of Drosophila aboard the International Space Station (ISS) for approximately 30 days, along with identical on-board 1-g controls as well as ground controls. The Drosophila will require minimal astronaut intervention involving changing feeding trays on 1 or 2 occasions. The samples will be retrieved post-flight and analyzed using established methods. Heart function, including measurements of diastolic and systolic intervals, heart rate, heart diameters, contractility, and arrhythmias will be recorded. Microscopic and immunohistochemical evaluations of heart morphology will also be carried out. We will also conduct intracellular membrane potential recordings of the heart. Finally, we will analyze mRNA expression with a microarray.

The ultimate goal of this research is to obtain data while validating the Drosophila model for studying the effects of spaceflight on cardiac disease and function. The development of such a model would be a potentially significant advancement in the study and understanding of how spaceflight affects the cardiovascular system, and may ultimately lead to countermeasures to prevent them.

Research Impact/Earth Benefits: Information about cardiac muscle function in microgravity is also expected to provide insights on genetic and molecular changes that occur with muscle atrophy on Earth. For example, we expect to identify basic molecular alterations that are associated with muscle atrophy that occurs during prolonged bed rest or muscle disuse in muscular dystrophies.

Task Progress & Bibliography Information FY2016 
Task Progress: Summary: This project uses the fruit fly heart model to understand the effects of microgravity on heart function. The fruit fly heart uses many of the same ion channels and beats at about the same rate as does the human heart, compared to the mouse heart that beats roughly 10 times faster. In a preliminary experiment we have demonstrated that we can get flies to reproduce on the ISS and adult flies born in microgravity were returned to us for study. Based on this initial test we are refining the conditions in preparation for a full scale experiment scheduled for SpaceX 11.

Bibliography: Description: (Last Updated: 06/23/2023) 

Show Cumulative Bibliography
 
 None in FY 2016
Project Title:  The Effects of Microgravity on Cardiac Function, Structure and Gene Expression using the Drosophila Model Reduce
Images: icon  Fiscal Year: FY 2015 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Invertebrate  
Start Date: 09/01/2013  
End Date: 09/30/2017  
Task Last Updated: 10/22/2015 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bodmer, Rolf  Ph.D. / Sanford-Burnham Medical Research Institute 
Address:  Development & Aging 
10901 N Torrey Pines Rd 
La Jolla , CA 92037-1005 
Email: rolf@sbpdiscovery.org 
Phone: 858-795-5295  
Congressional District: 49 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Sanford-Burnham Medical Research Institute 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bhattacharya, Sharmila  Ph.D. NASA Ames Research Center 
Ocorr, Karen  Ph.D. Burnham Institute for Medical Research 
Project Information: Grant/Contract No. NNX13AN38G 
Responsible Center: NASA ARC 
Grant Monitor: Smith, Jeffrey  
Center Contact: 650-604-0880 
jeffrey.d.smith2@nasa.gov 
Unique ID: 9354 
Solicitation / Funding Source: 2012 Space Biology NNH12ZTT001N 
Grant/Contract No.: NNX13AN38G 
Project Type: FLIGHT 
Flight Program: ISS 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Invertebrate
Space Biology Cross-Element Discipline: (1) Reproductive Biology
(2) Developmental Biology
(3) Musculoskeletal Biology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: ISS

NOTE: Extended to 9/30/2017 per NSSC information (Ed., 7/18/16)

NOTE: Extended to 12/31/2015 per NSSC information (Ed., 2/18/16)

NOTE: Extended to 10/31/2015 per NSSC information (Ed., 9/15/15)

Task Description: The detrimental effects of spaceflight on the cardiovascular system are well known. It is believed that these effects may lead to clinically significant risks to astronauts on long duration space missions as well as to the success of these missions themselves. Current studies are limited primarily to human studies and rodent experiments. However, these model systems and human studies have significant limitations that may be addressed by using the well-established Drosophila model. Drosophila have previously been successfully launched into space and a ground-based Drosophila model for cardiac disease and function has been developed. However, the genetically versatile Drosophila model has yet to be used for studying the effects of spaceflight on the cardiovascular system. We are currently preparing flies for a scheduled launch in Sept. 2015 and analyzing data from a preliminary space flown test of our experimental system.

In this proposal we propose to fly groups of Drosophila aboard the International Space Station for approximately 30 days, along with identical on-board 1-g controls as well as ground controls. The Drosophila will require minimal astronaut intervention involving changing feeding trays on 1 or 2 occasions. The samples will be retrieved post-flight and analyzed using established methods. Heart function, including measurements of diastolic and systolic intervals, heart rate, heart diameters, contractility, and arrhythmias will be recorded. Microscopic and immunohistochemical evaluations of heart morphology will also be carried out. We will also conduct intracellular membrane potential recordings of the heart. Finally, we will analyze mRNA expression with a microarray.

The ultimate goal of this research is to obtain data while validating the Drosophila model for studying the effects of spaceflight on cardiac disease and function. The development of such a model would be a potentially significant advancement in the study and understanding of how spaceflight affects the cardiovascular system, and may ultimately lead to countermeasures to prevent them.

Research Impact/Earth Benefits: Information about cardiac muscle function in microgravity is also expected to provide insights on genetic and molecular changes that occur with muscle atrophy on Earth. For example, we expect to identify basic molecular alterations that are associated with muscle atrophy that occurs during prolonged bed rest or muscle disuse in muscular dystrophies.

Task Progress & Bibliography Information FY2015 
Task Progress: The Space Florida Prize allowed us to launch fly groups of Drosophila aboard the April 18, 2014 Space-X3 mission. We received approximately 277 live adult flies and numerous pupae and larva when the box was returned to us on May 21, 2014. This was a pilot feasibility experiment to test if the fly might prove a useful model for microgravity effects on the heart and to determine if we would get sufficient live flies back. Now we are ready to perform the fully controlled experiments on approved Space-X11, tentatively scheduled for July 2016.

Our very positive preliminary results indicate that the responses of the fly heart to microgravity are similar to human responses. However, there were some problems that prevented us from obtaining optimal data and from obtaining full statistical power in our analyses. By refining the onboard protocol and by using multiple VFBs we will obtain sufficient material to perform numerous molecular biological and physiological experiments.

Bibliography: Description: (Last Updated: 06/23/2023) 

Show Cumulative Bibliography
 
Articles in Peer-reviewed Journals Martínez-Morentin L, Martínez L, Piloto S, Yang H, Schon EA, Garesse R, Bodmer R, Ocorr K, Cervera M, Arredondo JJ. "Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model." Hum Mol Genet. 2015 Jul 1;24(13):3608-22. Epub 2015 Mar 19. http://dx.doi.org/10.1093/hmg/ddv106 ; PubMed PMID: 25792727; PubMed Central PMCID: PMC4459388 , Jul-2015
Project Title:  The Effects of Microgravity on Cardiac Function, Structure and Gene Expression using the Drosophila Model Reduce
Images: icon  Fiscal Year: FY 2014 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Invertebrate  
Start Date: 09/01/2013  
End Date: 10/31/2015  
Task Last Updated: 01/07/2015 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bodmer, Rolf  Ph.D. / Sanford-Burnham Medical Research Institute 
Address:  Development & Aging 
10901 N Torrey Pines Rd 
La Jolla , CA 92037-1005 
Email: rolf@sbpdiscovery.org 
Phone: 858-795-5295  
Congressional District: 49 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Sanford-Burnham Medical Research Institute 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bhattacharya, Sharmila  Ph.D. NASA Ames Research Center 
Ocorr, Karen  Ph.D. Burnham Institute for Medical Research 
Project Information: Grant/Contract No. NNX13AN38G 
Responsible Center: NASA ARC 
Grant Monitor: Smith, Jeffrey  
Center Contact: 650-604-0880 
jeffrey.d.smith2@nasa.gov 
Unique ID: 9354 
Solicitation / Funding Source: 2012 Space Biology NNH12ZTT001N 
Grant/Contract No.: NNX13AN38G 
Project Type: FLIGHT 
Flight Program: ISS 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Invertebrate
Space Biology Cross-Element Discipline: (1) Reproductive Biology
(2) Developmental Biology
(3) Musculoskeletal Biology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: ISS

NOTE: Extended to 10/31/2015 per NSSC information (Ed., 9/15/15)

Task Description: The detrimental effects of spaceflight on the cardiovascular system are well known. It is believed that these effects may lead to clinically significant risks to astronauts on long duration space missions as well as to the success of these missions themselves. Current studies are limited primarily to human studies and rodent experiments. However, these model systems and human studies have significant limitations that may be addressed by using the well-established Drosophila model. Drosophila have previously been successfully launched into space and a ground-based Drosophila model for cardiac disease and function has been developed. However, the genetically versatile Drosophila model has yet to be used for studying the effects of spaceflight on the cardiovascular system. We are currently preparing flies for a scheduled launch in Sept. 2015 and analyzing data from a prelimnary space flown test of our experimental system.

In this proposal we propose to fly groups of Drosophila aboard the International Space Station for approximately 30 days, along with identical on-board 1-g controls as well as ground controls. The Drosophila will require minimal astronaut intervention involving changing feeding trays on 1 or 2 occasions. The samples will be retrieved post-flight and analyzed using established methods. Heart function, including measurements of diastolic and systolic intervals, heart rate, heart diameters, contractility, and arrhythmias will be recorded. Microscopic and immunohistochemical evaluations of heart morphology will also be carried out. We will also conduct intracellular membrane potential recordings of the heart. Finally, we will analyze mRNA expression with a microarray.

The ultimate goal of this research is to obtain data while validating the Drosophila model for studying the effects of spaceflight on cardiac disease and function. The development of such a model would be a potentially significant advancement in the study and understanding of how spaceflight affects the cardiovascular system, and may ultimately lead to countermeasures to prevent them.

Research Impact/Earth Benefits: Information about cardiac muscle function in microgravity is also expected to provide insights on genetic and molecular changes that occur with muscle atrophy on Earth. For example, we expect to identify basic molecular alterations that are associated with muscle atrophy that occurs during prolonged bed rest or muscle disuse in muscular dystrophies.

Task Progress & Bibliography Information FY2014 
Task Progress: We have sent a preliminary set of flies to the International Space Station (ISS) and have received back live flies that were born in space. We are currently analyzing the data from these flies and performing RNA sequencing of muscle and nervous tissue. This preliminary run has and will continue to provide important information (concerning numbers of flies we need and which genes to test further) that will allow us to maximize the data output from the next scheduled flight in September. We are also refining our abilities to extract data from the limited numbers of flies that return from the ISS.

We have also been testing the new Fruit Fly Lab 1 flight hardware that will be used on our next mission to see if it will provide similar results as the initial mission that used only a Nanoracks box.

Bibliography: Description: (Last Updated: 06/23/2023) 

Show Cumulative Bibliography
 
 None in FY 2014
Project Title:  The Effects of Microgravity on Cardiac Function, Structure and Gene Expression using the Drosophila Model Reduce
Images: icon  Fiscal Year: FY 2013 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Invertebrate  
Start Date: 09/01/2013  
End Date: 08/31/2015  
Task Last Updated: 07/29/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Bodmer, Rolf  Ph.D. / Sanford-Burnham Medical Research Institute 
Address:  Development & Aging 
10901 N Torrey Pines Rd 
La Jolla , CA 92037-1005 
Email: rolf@sbpdiscovery.org 
Phone: 858-795-5295  
Congressional District: 49 
Web:  
Organization Type: NON-PROFIT 
Organization Name: Sanford-Burnham Medical Research Institute 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bhattacharya, Sharmila  Ph.D. NASA Ames Research Center 
Ocorr, Karen  Ph.D. Burnham Institute for Medical Research 
Project Information: Grant/Contract No. NNX13AN38G 
Responsible Center: NASA ARC 
Grant Monitor: Smith, Jeffrey  
Center Contact: 650-604-0880 
jeffrey.d.smith2@nasa.gov 
Unique ID: 9354 
Solicitation / Funding Source: 2012 Space Biology NNH12ZTT001N 
Grant/Contract No.: NNX13AN38G 
Project Type: FLIGHT 
Flight Program: ISS 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Invertebrate
Space Biology Cross-Element Discipline: (1) Reproductive Biology
(2) Developmental Biology
(3) Musculoskeletal Biology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: ISS

Task Description: The detrimental effects of spaceflight on the cardiovascular system are well known. It is believed that these effects may lead to clinically significant risks to astronauts on long duration space missions as well as to the success of these missions themselves. Current studies are limited primarily to human studies and rodent experiments. However, these model systems have significant limitations that may be addressed by using the well-established Drosophila model. Drosophila have previously been successfully launched into space and a ground-based Drosophila model for cardiac disease and function has been developed. However, the genetically versatile Drosophila model has yet to be used for studying the effects of spaceflight on the cardiovascular system.

In this proposal we propose to fly groups of Drosophila aboard the International Space Station for approximately 30 days, along with identical on-board 1-g controls as well as ground controls. The Drosophila will require minimal astronaut intervention involving changing feeding trays on 1 or 2 occasions. The samples will be retrieved post-flight and analyzed using established methods. Heart function, including measurements of diastolic and systolic intervals, heart rate, heart diameters, contractility, and arrhythmias will be recorded. Microscopic and immunohistochemical evaluations of heart morphology will also be carried out. We will also conduct intracellular membrane potential recordings of the heart. Finally, we will analyze mRNA expression with a microarray.

The ultimate goal of this research is to obtain data while validating the Drosophila model for studying the effects of spaceflight on cardiac disease and function. The development of such a model would be a potentially significant advancement in the study and understanding of how spaceflight affects the cardiovascular system, and may ultimately lead to countermeasures to prevent them.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2013 
Task Progress: New project for FY2013.

Bibliography: Description: (Last Updated: 06/23/2023) 

Show Cumulative Bibliography
 
 None in FY 2013