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Project Title:  Contributions of the Microbiome in Astronaut Health: a New Dimension in Modeling Crew Infectious Disease Risks Reduce
Fiscal Year: FY 2022 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Microbiology  
Start Date: 10/01/2018  
End Date: 09/30/2022  
Task Last Updated: 07/21/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Nickerson, Cheryl A Ph.D. / Arizona State University 
Address:  Center for Infectious Diseases and Vaccinology/The Biodesign Institute 
1001 S McAllister Avenue 
Tempe , AZ 85287-5401 
Email: Cheryl.Nickerson@asu.edu 
Phone: 480-727-7520  
Congressional District:
Web: https://sols.asu.edu/people/cheryl-nickerson  
Organization Type: UNIVERSITY 
Organization Name: Arizona State University 
Joint Agency:  
Comments: NOTE PI moved from Tulane University to Arizona State University in 2006. 
Co-Investigator(s)
Affiliation: 
Bean, Heather   Ph.D. Arizona State University 
Barrila, Jennifer  Ph.D. Arizona State University 
Ott, C. Mark  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. 80NSSC18K1478 
Responsible Center: NASA KSC 
Grant Monitor: Freeland, Denise  
Center Contact: 321-867-5878 
Denise.E.Freeland@nasa.gov 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-MS, PS, AB. App D,E,F: Research Using Microgravity Simulation Devices, Parabolic and Suborbital Flights, and Antarctic Balloons 
Grant/Contract No.: 80NSSC18K1478 
Project Type: GROUND 
Flight Program:  
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) Cell & Molecular Biology
(2) Microbiology
Space Biology Cross-Element Discipline: (1) Immunology
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: NOTE: End date changed to 9/30/2022 per NSSC information (Ed., 9/23/21)

Task Description: The diverse communities of microbes that reside in the human intestinal tract play critical roles in the prevention of enteric infection for both astronauts and the general public. A comprehensive understanding of how changes in gut microbiota composition impacts susceptibility to infection has been limited by a lack of cost-effective, physiologically relevant infection models containing both human host and microbial cells. We previously developed an advanced three-dimensional (3-D) model of human colon containing inflammatory immune cells and applied it to study host-pathogen interactions, including the influence of low fluid shear microgravity analogue culture on the ability of the enteric pathogen Salmonella to colonize the host. This same model was also applied to study host-microbiota interactions using patient-derived fecal consortia from both healthy individuals and those suffering from a gastrointestinal disorder. For the proposed study, our goal is to populate our 3-D intestinal co-culture model containing immune cells with astronaut fecal microbiota (previously collected during the Microbiome spaceflight experiment) and assess its influence on infection with Salmonella cultured under microgravity analogue conditions. The outcome of these interactions will be profiled using a variety of approaches, including colonization studies, microscopy, metabolomics, 16S analysis, and cytokine analysis. The foodborne pathogen Salmonella was selected as the model pathogen as it is a leading cause of gastrointestinal disease worldwide and imposes an enormous health and socioeconomic burden. From NASA's perspective, Salmonella is considered a potential source of infection during spaceflight that could incapacitate crew members during a mission. Due to its route of access through spaceflight food, NASA specifically tests for Salmonella prior to flight and has previously disqualified food destined for the International Space Station based on the isolation of this pathogen. The proposed microgravity analogue studies combine microbiology, tissue engineering, and physics to provide new insight into the influence of spaceflight on host-microbiome interactions and the ability to protect against pathogen infection with applications for therapeutic development for spaceflight exploration and health of the general public.

Research Impact/Earth Benefits: This research will enrich life on Earth through the use of space technology and the application of biomedical knowledge. Specifically, this study will utilize the microgravity spaceflight platform to 1) to broaden our knowledge of the host-pathogen interaction that leads to infectious disease, and 2) for the development of new therapeutic strategies to combat infectious disease for astronauts and the general public.

Task Progress & Bibliography Information FY2022 
Task Progress: While we have made progress on this project, including advancing scientific objectives at the bench, as well submission and publication of multiple manuscripts, we have still encountered some delays due to significant COVID-19-related health issues to lead personnel on this project, as well as routine access to our lab. We are thus respectfully requesting a NCE (no-cost extension) to successfully complete our funded objectives.

Invited Presentations during the reporting period:

Invited speaker, Biomedical Advanced Research and Development Authority (BARDA), March 16, 2020.

Invited speaker, 21st Century Research – Moving Beyond Animals in the Neurosciences and Infectious Disease Research, Arizona State University, Tempe, AZ, April 24, 2020

Invited speaker, American Society for Space and Gravitational Research (ASGSR) Decadal Workshop: Space Microbiology Town Hall. October 14, 2020

Invited speaker, Infectious Diseases and Global Health Training Program, University of Manitoba, Nov 26, 2020

Invited speaker and panelist, New York Health Forum "Investing in Space – Next Frontier of Healthcare", March 16, 2021

Invited speaker, Gastronauts Global Symposium, “Where the Gut Meets the Brain”, Virtual Meeting, May 19-22, 2021

Bibliography Type: Description: (Last Updated: 12/28/2021)  Show Cumulative Bibliography Listing
 
Articles in Other Journals or Periodicals Nickerson CA, Colorado A, Barrila J, Poste G, Ott CM. "A vision for the next generation of spaceflight microbiology: human health and habitat sustainability." Nature Microbiology. Under revision, as of July 2021. Invited Review. , Jul-2021
Articles in Peer-reviewed Journals Barrila J, Sarker SF, Hansmeier N, Yang S, Buss K, Briones N, Park J, Davis RR, Forsyth RJ, Ott CM, Sato K, Kosnik C, Yang A, Shimoda C, Rayl N, Ly D, Landenberger A, Wilson SD, Yamazaki N, Steel J, Montano C, Halden RU, Cannon T, Castro-Wallace SL, Nickerson CA. "Evaluating the effect of spaceflight on the host–pathogen interaction between human intestinal epithelial cells and Salmonella Typhimurium." npj Microgravity. 2021 Mar 9;7(1):9. https://doi.org/10.1038/s41526-021-00136-w ; PMID: 33750813; PMCID: PMC7943786 , Mar-2021
Project Title:  Contributions of the Microbiome in Astronaut Health: a New Dimension in Modeling Crew Infectious Disease Risks Reduce
Fiscal Year: FY 2021 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Microbiology  
Start Date: 10/01/2018  
End Date: 09/30/2021  
Task Last Updated: 08/04/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Nickerson, Cheryl A Ph.D. / Arizona State University 
Address:  Center for Infectious Diseases and Vaccinology/The Biodesign Institute 
1001 S McAllister Avenue 
Tempe , AZ 85287-5401 
Email: Cheryl.Nickerson@asu.edu 
Phone: 480-727-7520  
Congressional District:
Web: https://sols.asu.edu/people/cheryl-nickerson  
Organization Type: UNIVERSITY 
Organization Name: Arizona State University 
Joint Agency:  
Comments: NOTE PI moved from Tulane University to Arizona State University in 2006. 
Co-Investigator(s)
Affiliation: 
Bean, Heather   Ph.D. Arizona State University 
Barrila, Jennifer  Ph.D. Arizona State University 
Ott, C. Mark  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. 80NSSC18K1478 
Responsible Center: NASA KSC 
Grant Monitor: Freeland, Denise  
Center Contact: 321-867-5878 
Denise.E.Freeland@nasa.gov 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-MS, PS, AB. App D,E,F: Research Using Microgravity Simulation Devices, Parabolic and Suborbital Flights, and Antarctic Balloons 
Grant/Contract No.: 80NSSC18K1478 
Project Type: GROUND 
Flight Program:  
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) Cell & Molecular Biology
(2) Microbiology
Space Biology Cross-Element Discipline: (1) Immunology
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Task Description: The diverse communities of microbes that reside in the human intestinal tract play critical roles in the prevention of enteric infection for both astronauts and the general public. A comprehensive understanding of how changes in gut microbiota composition impacts susceptibility to infection has been limited by a lack of cost-effective, physiologically relevant infection models containing both human host and microbial cells. We previously developed an advanced three-dimensional (3-D) model of human colon containing inflammatory immune cells and applied it to study host-pathogen interactions, including the influence of low fluid shear microgravity analogue culture on the ability of the enteric pathogen Salmonella to colonize the host. This same model was also applied to study host-microbiota interactions using patient-derived fecal consortia from both healthy individuals and those suffering from a gastrointestinal disorder. For the proposed study, our goal is to populate our 3-D intestinal co-culture model containing immune cells with astronaut fecal microbiota (previously collected during the Microbiome spaceflight experiment) and assess its influence on infection with Salmonella cultured under microgravity analogue conditions. The outcome of these interactions will be profiled using a variety of approaches, including colonization studies, microscopy, metabolomics, 16S analysis, and cytokine analysis. The foodborne pathogen Salmonella was selected as the model pathogen as it is a leading cause of gastrointestinal disease worldwide and imposes an enormous health and socioeconomic burden. From NASA's perspective, Salmonella is considered a potential source of infection during spaceflight that could incapacitate crew members during a mission. Due to its route of access through spaceflight food, NASA specifically tests for Salmonella prior to flight and has previously disqualified food destined for the International Space Station based on the isolation of this pathogen. The proposed microgravity analogue studies combine microbiology, tissue engineering, and physics to provide new insight into the influence of spaceflight on host-microbiome interactions and the ability to protect against pathogen infection with applications for therapeutic development for spaceflight exploration and health of the general public.

Research Impact/Earth Benefits: This research will enrich life on Earth through the use of space technology and the application of biomedical knowledge. Specifically, this study will utilize the microgravity spaceflight platform to 1) to broaden our knowledge of the host-pathogen interaction that leads to infectious disease, and 2) for the development of new therapeutic strategies to combat infectious disease for astronauts and the general public.

Task Progress & Bibliography Information FY2021 
Task Progress: Due to the combination of an extended duration medical recovery for our lead bench scientist for this work, combined with the lack of research access to our laboratory due to COVID-19 since March, we have experienced a significant delay in our ability to progress at the bench on this project. Given the dynamic situation of COVID-19, especially in Phoenix AZ, where infection rates have been among the highest in the country, we currently anticipate being able to return to bench work on this project in September.

Invited Presentations during the reporting period:

Invited speaker, American Society for Microbiology (ASM) Distinguished Lecturer, North Carolina Branch ASM, Greensboro, NC, October 19, 2019.

Invited speaker, “3D Tissues and Microphysiological Systems,” National Institutes of Health/The National Center for Advancing Translational Sciences (NIH/NCATS) pre-workshop, American Society for Gravitational and Space Research Annual Meeting, Denver, CO, Nov 19, 2019.

Bibliography Type: Description: (Last Updated: 12/28/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2021
Project Title:  Contributions of the Microbiome in Astronaut Health: a New Dimension in Modeling Crew Infectious Disease Risks Reduce
Fiscal Year: FY 2020 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Microbiology  
Start Date: 10/01/2018  
End Date: 09/30/2021  
Task Last Updated: 08/05/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Nickerson, Cheryl A Ph.D. / Arizona State University 
Address:  Center for Infectious Diseases and Vaccinology/The Biodesign Institute 
1001 S McAllister Avenue 
Tempe , AZ 85287-5401 
Email: Cheryl.Nickerson@asu.edu 
Phone: 480-727-7520  
Congressional District:
Web: https://sols.asu.edu/people/cheryl-nickerson  
Organization Type: UNIVERSITY 
Organization Name: Arizona State University 
Joint Agency:  
Comments: NOTE PI moved from Tulane University to Arizona State University in 2006. 
Co-Investigator(s)
Affiliation: 
Bean, Heather   Ph.D. Arizona State University 
Barrila, Jennifer  Ph.D. Arizona State University 
Ott, C. Mark  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. 80NSSC18K1478 
Responsible Center: NASA KSC 
Grant Monitor: Freeland, Denise  
Center Contact: 321-867-5878 
Denise.E.Freeland@nasa.gov 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-MS, PS, AB. App D,E,F: Research Using Microgravity Simulation Devices, Parabolic and Suborbital Flights, and Antarctic Balloons 
Grant/Contract No.: 80NSSC18K1478 
Project Type: GROUND 
Flight Program:  
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) Cell & Molecular Biology
(2) Microbiology
Space Biology Cross-Element Discipline: (1) Immunology
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Task Description: The diverse communities of microbes that reside in the human intestinal tract play critical roles in the prevention of enteric infection for both astronauts and the general public. A comprehensive understanding of how changes in gut microbiota composition impacts susceptibility to infection has been limited by a lack of cost-effective, physiologically relevant infection models containing both human host and microbial cells. We previously developed an advanced three-dimensional (3-D) model of human colon containing inflammatory immune cells and applied it to study host-pathogen interactions, including the influence of low fluid shear microgravity analogue culture on the ability of the enteric pathogen Salmonella to colonize the host. This same model was also applied to study host-microbiota interactions using patient-derived fecal consortia from both healthy individuals and those suffering from a gastrointestinal disorder. For the proposed study, our goal is to populate our 3-D intestinal co-culture model containing immune cells with astronaut fecal microbiota (previously collected during the Microbiome spaceflight experiment) and assess its influence on infection with Salmonella cultured under microgravity analogue conditions. The outcome of these interactions will be profiled using a variety of approaches, including colonization studies, microscopy, metabolomics, 16S analysis, and cytokine analysis. The foodborne pathogen Salmonella was selected as the model pathogen as it is a leading cause of gastrointestinal disease worldwide and imposes an enormous health and socioeconomic burden. From NASA's perspective, Salmonella is considered a potential source of infection during spaceflight that could incapacitate crew members during a mission. Due to its route of access through spaceflight food, NASA specifically tests for Salmonella prior to flight and has previously disqualified food destined for the International Space Station based on the isolation of this pathogen. The proposed microgravity analogue studies combine microbiology, tissue engineering, and physics to provide new insight into the influence of spaceflight on host-microbiome interactions and the ability to protect against pathogen infection with applications for therapeutic development for spaceflight exploration and health of the general public.

Research Impact/Earth Benefits: This research will enrich life on Earth through the use of space technology and the application of biomedical knowledge. Specifically, this study will utilize the microgravity spaceflight platform to 1) to broaden our knowledge of the host-pathogen interaction that leads to infectious disease, and 2) for the development of new therapeutic strategies to combat infectious disease for astronauts and the general public.

Task Progress & Bibliography Information FY2020 
Task Progress: Trained key lab personnel to perform 3-D cell culture, including media preparation, development of 3-D intestinal co-culture model, counting, seeding and infection of 3-D models with rotating wall vessel (RWV)-cultured Salmonella, and confocal imaging of 3-D models. Multiple team members also received training on fecal microbiota handling and preparation, use of the Bioplex to perform cytokine analyses of 3-D intestinal co-culture model and attended flow cytometry training.

Successfully optimized infection procedures of the 3-D intestinal co-culture models under relevant environmental conditions in the glovebox using RWV-cultured Salmonella in the presence and absence of human fecal microbiota. This included testing of selective/differential media for microbial plating.

Received astronaut fecal samples from our collaborator at J Craig Venter Institute (JCVI), Hernan Lorenzi. Currently finalizing plans to incorporate these samples into our 3-D models.

Invited Presentations:

C. Nickerson:

Invited panelist and speaker, Leading Women: Biotech and Beyond, Phoenix Convention Center, Phoenix, AZ, October 1, 2018

Invited speaker, University of Louisville, Department of Microbiology and Immunology, Louisville, KY, Oct 4, 2018

Invited speaker, ASM Distinguished Lecturer, Eastern New York Branch ASM, Albany, NY, October 16, 2018

Invited Speaker, Gastronauts, Duke University, Durham, NC, Feb 5, 2019

Invited speaker, ASM Distinguished Lecturer, Missouri Valley Branch ASM, Omaha, NB, March 15-16, 2019

Invited speaker, 3D Tissue Infection Symposium, Wuerzburg, Germany, April 5-7, 2019

Invited Speaker, Nature-NASA Conference on “The Microbiology of Human Spaceflight”, Johnson Space Center, Houston, TX June 24-27, 2019

Invited Speaker, NIH-NASA Summer 2019 Seminar Series, “Microbial pathogen responses to biomechanical forces in infected hosts and microgravity environments”, webinar, July 11, 2019

J. Barrila:

Dynamic low fluid shear suspension culture enhances the host-pathogen interaction between Salmonella and a human 3-D intestinal co-culture model. * Invited presentation. 3D Tissue Infection Symposium. Wuerzburg, Germany. April 5-7 2019.

Bibliography Type: Description: (Last Updated: 12/28/2021)  Show Cumulative Bibliography Listing
 
Awards Barrila J. "Presidential Early Career Award for Scientists and Engineers (PECASE) presented to Jennifer Barrila, CoInvestigator. She is one of 18 NASA researcher awardees. July 2019." Jul-2019
Project Title:  Contributions of the Microbiome in Astronaut Health: a New Dimension in Modeling Crew Infectious Disease Risks Reduce
Fiscal Year: FY 2019 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Microbiology  
Start Date: 10/01/2018  
End Date: 09/30/2021  
Task Last Updated: 10/25/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Nickerson, Cheryl A Ph.D. / Arizona State University 
Address:  Center for Infectious Diseases and Vaccinology/The Biodesign Institute 
1001 S McAllister Avenue 
Tempe , AZ 85287-5401 
Email: Cheryl.Nickerson@asu.edu 
Phone: 480-727-7520  
Congressional District:
Web: https://sols.asu.edu/people/cheryl-nickerson  
Organization Type: UNIVERSITY 
Organization Name: Arizona State University 
Joint Agency:  
Comments: NOTE PI moved from Tulane University to Arizona State University in 2006. 
Co-Investigator(s)
Affiliation: 
Bean, Heather   Ph.D. Arizona State University 
Barrila, Jennifer  Ph.D. Arizona State University 
Ott, C. Mark  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. 80NSSC18K1478 
Responsible Center: NASA KSC 
Grant Monitor: Freeland, Denise  
Center Contact: 321-867-5878 
Denise.E.Freeland@nasa.gov 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-MS, PS, AB. App D,E,F: Research Using Microgravity Simulation Devices, Parabolic and Suborbital Flights, and Antarctic Balloons 
Grant/Contract No.: 80NSSC18K1478 
Project Type: GROUND 
Flight Program:  
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) Cell & Molecular Biology
(2) Microbiology
Space Biology Cross-Element Discipline: (1) Immunology
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Task Description: The diverse communities of microbes that reside in the human intestinal tract play critical roles in the prevention of enteric infection for both astronauts and the general public. A comprehensive understanding of how changes in gut microbiota composition impacts susceptibility to infection has been limited by a lack of cost-effective, physiologically relevant infection models containing both human host and microbial cells. We previously developed an advanced three-dimensional (3-D) model of human colon containing inflammatory immune cells and applied it to study host-pathogen interactions, including the influence of low fluid shear microgravity analogue culture on the ability of the enteric pathogen Salmonella to colonize the host. This same model was also applied to study host-microbiota interactions using patient-derived fecal consortia from both healthy individuals and those suffering from a gastrointestinal disorder. For the proposed study, our goal is to populate our 3-D intestinal co-culture model containing immune cells with astronaut fecal microbiota (previously collected during the Microbiome spaceflight experiment) and assess its influence on infection with Salmonella cultured under microgravity analogue conditions. The outcome of these interactions will be profiled using a variety of approaches, including colonization studies, microscopy, metabolomics, 16S analysis, and cytokine analysis. The foodborne pathogen Salmonella was selected as the model pathogen as it is a leading cause of gastrointestinal disease worldwide and imposes an enormous health and socioeconomic burden. From NASA's perspective, Salmonella is considered a potential source of infection during spaceflight that could incapacitate crew members during a mission. Due to its route of access through spaceflight food, NASA specifically tests for Salmonella prior to flight and has previously disqualified food destined for the International Space Station based on the isolation of this pathogen. The proposed microgravity analogue studies combine microbiology, tissue engineering, and physics to provide new insight into the influence of spaceflight on host-microbiome interactions and the ability to protect against pathogen infection with applications for therapeutic development for spaceflight exploration and health of the general public.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2019 
Task Progress: New project for FY2019.

Bibliography Type: Description: (Last Updated: 12/28/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2019