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Project Title:  Megakaryocytes Orbiting in Outer Space and Near Earth: The MOON Study Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology  
Start Date: 12/01/2021  
End Date: 11/30/2024  
Task Last Updated: 03/25/2022 
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Principal Investigator/Affiliation:   Schwertz, Hansjorg  M.D., Ph.D. / University of Utah, Salt Lake City 
Address:  Department of Family and Preventive Medicine 
391 S Chipeta Way, Suite C 
Salt Lake City , UT 84108-1263 
Email: hansjorg.schwertz@u2m2.utah.edu 
Phone: 801-946-0924  
Congressional District:
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Organization Type: UNIVERSITY 
Organization Name: University of Utah, Salt Lake City 
Joint Agency:  
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Co-Investigator(s)
Affiliation: 
Rondina, Matthew  M.D. University of Utah, Salt Lake City 
Rowley, Jesse  Ph.D. University of Utah, Salt Lake City 
Project Information: Grant/Contract No. 80NSSC22K0255 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Yuri.V.Griko@nasa.gov 
Solicitation / Funding Source: 2020 Space Biology NNH20ZDA001N-SB E.12. Flight/Ground Research 
Grant/Contract No.: 80NSSC22K0255 
Project Type: FLIGHT 
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Space Biology Element: (1) Cell & Molecular Biology
Space Biology Cross-Element Discipline: (1) Immunology
Space Biology Special Category: None
Task Description: Megakaryocytes (MKs) and their progeny, platelets (PLTs), are dynamic effector cells with recently discovered novel functions, which bridge the inflammatory, immune, and hemostatic continuum. Changes in bone marrow MKs, resulting in low PLT numbers, (thrombocytopenia, which occurs in astronauts during spaceflight) are associated with dysregulated host inflammatory/immune responses. MKs and PLTs sense and respond to environmental cues. MKs also differentially invest developing PLTs with RNAs and proteins that alter functions of newly-released cells, influencing cellular and host responses. Surprisingly, there is a paucity of data regarding in-flight, long-term dynamics of MK development and function, as well as PLT function and production. Given previously identified and published space-travel associated risks on dysregulated inflammation, immune responses, thrombus formation, and hemostatic systems, filling this critical knowledge gap is important for the health of spaceflight crewmembers during and after missions. Moreover, as other blood cells (e.g., red blood cells, leukocytes, etc.) may be altered by microgravity, data generated are likely to contribute to our understanding of how spaceflight affects other hematopoietic processes.

This proposal is based on our robust preliminary data demonstrating that conditions mimicking microgravity (rotating wall vessel culture, RWVC) markedly alter human MK morphology and gene expression. We hypothesize that microgravity will re-program MKs and newly-released PLTs, resulting in critical changes in their transcriptome, proteome, and alterations in PLT number and function. We will determine how microgravity and space radiation conditions on board the International Space Station (ISS) alter human MK and PLT maturation/production, gene expression (DNA, RNA, and protein), and cellular function. We will study in vitro human hematopoietic progenitor cell (HPC)-derived MKs in Earth-based experiments under standard or microgravity conditions. In parallel, human MKs will be studied on the ISS. Integrated, cutting-edge OMICS toolsets (e.g., RNA-sequencing and ribosomal footprinting [Ribo-seq]), comprehensive morphologic studies, and cell production kinetic studies will be used. They will provide unprecedented insight into adaptation processes needed for MK and PLT function under conditions experienced by humans performing spaceflights. These studies will directly address crew health concerns that currently limit human space exploration and will assist in developing targeted countermeasures.

This proposal concurs with the major National Research Council (NRC) Decadal Survey Recommendations for cellular and molecular biology studies using state- of-the-art tools coupled with systems biology, and for studies evaluating the physiological interplay of cardiopulmonary and immune functions during application of spaceflight. Furthermore, we will address goals of the NASA Space Biology Science Plan 2016-2025, including: (1) determine the effects of the space environment on DNA function, (2) develop a systems biology-based understanding of the cellular and molecular changes to explain how gravitational changes in spaceflight effects organisms and causes phenotypic changes, and (3) identify how spaceflight affects the ability of cells to generate and maintain their complex internal cyto-architecture, processes critical for MKs and PLTs.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2022 
Task Progress: New project for FY2022.

Bibliography Type: Description: (Last Updated: ) 

Show Cumulative Bibliography Listing
 
 None in FY 2022