Investigation of host-pathogen interactions, conserved cellular responses, and countermeasure efficacy during spaceflight using the human surrogate model Caenorhabditis elegans (Micro-5) - 11.12.14

Overview | Description | Applications | Operations | Results | Publications | Imagery
ISS Science for Everyone

Science Objectives for Everyone
The Investigation of host-pathogen interactions, conserved cellular responses, and countermeasure efficacy during spaceflight using the human surrogate model Caenorhabditis elegans (Micro-5) aims to better understand the risks of in-flight infections in space explorers during long-term space flight, using the model organism Caenorhabditis elegans (roundworm) with the microbe Salmonella typhimurium (that causes food poisoning in humans).

Science Results for Everyone
Information Pending



The following content was provided by Cheryl A. Nickerson, Ph.D., and is maintained in a database by the ISS Program Science Office.

Experiment Details

OpNom Micro-5

Principal Investigator(s)

  • Cheryl A. Nickerson, Ph.D., Arizona State University, Tempe, AZ, United States

  • Co-Investigator(s)/Collaborator(s)
  • Charlie Mark Ott, Ph.D., Johnson Space Center, Houston, TX, United States

  • Developer(s)
    University of Colorado at Boulder, BioServe Space Technologies, Boulder, CO, United States

    BioServe Space Technologies, University of Colorado, Boulder, CO, United States

    Sponsoring Space Agency
    National Aeronautics and Space Administration (NASA)

    Sponsoring Organization
    Human Exploration and Operations Mission Directorate (HEOMD)

    Research Benefits
    Earth Benefits, Scientific Discovery, Space Exploration

    ISS Expedition Duration
    September 2014 - March 2015

    Expeditions Assigned
    41/42

    Previous ISS Missions
    Microbe (STS-115), STL-Immune (STS-131), Micro-4 (STS-135)

    ^ back to top



    Experiment Description

    Research Overview
    Improving the understanding of the risk due to infectious disease becomes critical to ensure crew health, safety, and performance during long duration missions. Changes that occur to both the human immune system and the pathogens could represent a major challenge to the successful transition from short- to long-duration space flight.

    • The Micro-5 experiment infects the human surrogate model Caenorhabditis elegans with S. typhimurium during space flight, and follows the survival of the C. elegans roundworms on orbit, compared to controls on Earth.
    • Micro-5 studies the role of the intestine during infections in real-time, defines virulence mechanisms, identifies evolutionarily conserved responses, and tests novel therapeutic strategies to prevent infectious disease.

    Description
    Changes that occur to both the host immune system and pathogenesis of microbes during space flight represent a difficult challenge to the successful transition from short to long-duration space flight. This is a critical concern since; a) the immune system of the crew is dysfunctional during spaceflight, b) spaceflight uniquely increases the virulence and globally alters gene expression of the human pathogen Salmonella typhimurium when the bacteria are recovered post-flight and subsequently used to infect ground-based animal models, c) spaceflight-induced increases in S. typhimurium virulence are regulated by media ion composition, d) phosphate ion is sufficient to alter related pathogenesis responses in a ground-based space flight analogue model, and e) the evolutionarily conserved bacterial RNA chaperone protein, Hfq, serves as a master molecular regulator of many of these responses.

    While space flight has been shown to induce changes that can independently affect the host or the pathogen in a manner that is directly relevant to the development of infectious disease during space flight, none of these studies have been done when both the host and pathogen are simultaneously exposed to the space flight environment. To address this, the Micro-5 experiment studies in-flight infections of Caenorhabditis elegans with S. typhimurium to observe the role of the intestine in host-pathogen interactions in real-time, define virulence mechanisms, identify evolutionarily conserved responses, and test novel therapeutic strategies to prevent infectious disease.

    The Micro-5 investigators hypothesize that the combination of a space flight induced increase in virulence of the pathogen coupled with a blunted immune response of the host will result in a synergistic effect on the host-pathogen interaction, such that the risk of infectious disease during space flight is worsened. Investigators further propose that these responses represent evolutionarily conserved mechanisms at the level of both host and pathogen that are dependent on media ion composition, specifically the local concentration of phosphate.

    ^ back to top



    Applications

    Space Applications
    Improved understanding of the risk due to infectious disease becomes critical to ensure crew health, safety and performance during long duration missions. Changes that occur to both the host immune system and pathogenesis of microbes during space flight could represent a formidable challenge to the successful transition from short to long-duration space flight. This is a critical issue to address since the crew’s immune system is dysfunctional during flight, and space flight uniquely increases the virulence and globally alters gene expression of pathogens such as Salmonella typhimurium. However, none of these studies have been done when both the host and pathogen are simultaneously exposed to the space flight environment. To address this, the Micro-5 experiment studies the infection of Caenorhabditis elegans with S. typhimurium during space flight and observe the effects in real-time. This experiment also tests novel therapeutic strategies to prevent infectious diseases during future space flight missions.

    Earth Applications
    The Micro-5 study is the first of its kind to profile the host-pathogen interaction in real time during space flight. This study provides a solid foundation for the development of vaccines and other novel countermeasures, for the treatment and prevention of infectious diseases both to the crew and the general public on Earth. Most importantly, the knowledge gained from this experiment broadens the knowledge of microorganisms and mammalian cells for both space flight and Earth-based applications.

    ^ back to top



    Operations

    Operational Requirements

    • Late Load L- 28 hrs
    • Early Recovery of samples once returned to Earth.
    • Microgravity Science Glovebox required.
    • Crew interaction required for transfer from Dragon and for science operations on three separate days. Crew activates the bacteria, inoculates samples, takes samples, stows samples in 4°C or -80°C, and places hardware in front of ScanCam within the Commercial Generic Bioprocessing Apparatus (CGBA) for video imaging that occurs for 7-14 days. (Imaging is controlled from the ground and does not require crew interaction other than for insertion and removal of samples into/from imaging bracket).

    Operational Protocols
    The payload is transferred from the Dragon Spacecraft and stowed in the appropriate locations. 
     
    On operations day 1 the crew adds bacteria inoculum into a growth bag (8 growth bags total).  The growth bags are returned to CGBA incubator for temperature control (25°C).
     
    On operations day 2 the crew adds bacteria that have been cultured for ~24 hours from the growth bags to the BioCell hardware that contains the nematodes.  After mixing the bacteria and nematodes, a small amount of the mixture is withdrawn from each BioCell and transferred into two six-well BioCells for video imaging.  The six-well BioCells are placed in front of the BioServe ScanCams inside of 2 different CGBAs.  Video imaging of the six-well BioCell occurs 1-2 times a day for 7-14 days while CGBA maintains temperature control of 25°C.  Also on operations day 2, a sample is pulled from each of the 8 bacteria growth bags and placed in a 4°C refrigerator for return to Earth.  The single well BioCells are returned to separate (third) CGBA for temperature control (25°C).
     
    On operations day 4 the crew pulls two samples from each single well BioCell.  Half of the samples are placed in 4°C stowage and the other half are placed in -80°C stowage.  The -80°C samples are frozen quickly by utilizing pre-chilled freezing blocks.   
     
    All samples are maintained at the appropriate stowage temperature when packed onto Dragon for return to Earth. 
     
    Datadownlink at certain time points is required in order to receive all video files on the ground from CGBA.

    ^ back to top



    Results/More Information
    Information Pending

    ^ back to top



    Related Websites
    Science Daily - Out of This World: New Study Investigates Infection of Human Cells in Space

    ^ back to top



    Imagery

    image Microscopic view of Salmonella typhimurium bacteria.
    + View Larger Image


    image Microscopic view of the roundworm C. elegans
    + View Larger Image