ISS National Laboratory Pathfinder Missions


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Jeanne L. Becker, PhD, 2010 American Astronautical Society Goddard Memorial Symposium

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  • The end point, or the effect is that microbes change in microgravity. The consequences surrounding this effect this may be associated with bacterial growth, its susceptibility to antibiotics, its pathogenicity or ability to cause disease, and its virulence or potency.
  • For this work, our approach was to go to the published literature, and take advantage of the scientific evidence to point us towards the gene candidates for Salmonella enteritidis known to be associated with virulence, hence be a potential target for future vaccine development
  • We knew C elegans would work well, since it has been flown before, and known to survive well in the environment of spaceflight, and the BioServe group has experience in flying the organism
  • Heidemarie Stefanyshyn-Piper STS-126 November 20, 2008
  • John Phillips STS-119 March 18, 2009
  • John Phillips STS-119 March 18, 2009
  • ISS National Laboratory Pathfinder Missions

    1. 1. ISS National Laboratory Pathfinder Missions Therapeutics for Infectious Disease Jeanne L. Becker, Ph.D.
    2. 2. Overview: Therapeutics for Infectious Disease <ul><li>Academic – Industry partnership </li></ul><ul><li>Uses microgravity exposure to uncover new targets for treatment against microbes </li></ul><ul><li>ISS National Laboratory Pathfinder Vaccine (NLP-V) Missions </li></ul><ul><li>Validates the utilization of space for commercial development </li></ul><ul><li>NASA provides flight opportunities to accomplish commercial development goals </li></ul>
    3. 3. <ul><li>Partners </li></ul><ul><li>Academic : </li></ul><ul><li>Durham VA Medical Center </li></ul><ul><li>Duke University </li></ul><ul><li>Max Planck Institute for Infection Biology </li></ul><ul><li>Hardware Provider : </li></ul><ul><li>BioServe Space Technologies </li></ul><ul><li>Industry : </li></ul><ul><li>Astrotech / Astrogenetix </li></ul>
    4. 4. <ul><li> Why space? </li></ul><ul><li>Effect : Growth within the space environment induces changes in microbial cells. </li></ul><ul><li>Result : These changes are may be associated with: </li></ul><ul><ul><ul><ul><ul><li>Growth </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Antibiotic resistance </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Pathogenicity </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Virulence </li></ul></ul></ul></ul></ul><ul><li>Strategy : Take advantage of new knowledge uncovered by exposure to microgravity to treat infectious disease. </li></ul>
    5. 5. An experiment conducted on the space shuttle demonstrated that Salmonella grown in space becomes more virulent, as compared to the same bacteria grown here on earth
    6. 6. <ul><ul><li>A good vaccine must be: </li></ul></ul><ul><ul><li>Strong enough to induce an adequate immune response </li></ul></ul><ul><ul><li>Strong enough to provide protection from future Salmonella exposure </li></ul></ul><ul><ul><li>Weak enough to allow administration with little or no risk of illness </li></ul></ul>If the cause of the increased virulence could be determined, can this knowledge be used to create a vaccine?
    7. 7. <ul><li>Scientific Approach </li></ul><ul><li>Leveraged ground-based work to identifying genes as candidate virulence factors </li></ul><ul><li>Leveraged ground-based assays to optimize host-microbe interactions </li></ul><ul><li>Leveraged existing flight experimental hardware </li></ul><ul><li>Developed an in-flight virulence assay </li></ul>
    8. 8. <ul><li>Model organism used is Caenorhabditis elegans , a small (1 mm long) soil nematode </li></ul><ul><li>Eats bacteria, such as Salmonella </li></ul><ul><li>Reports bacterial virulence (ability to cause disease ) </li></ul>
    9. 9. <ul><li>Bacteria and worms launched </li></ul><ul><li>Brought together in space </li></ul><ul><li>If bacteria remain virulent, worms are killed, bacteria grow </li></ul><ul><li>If bacteria lose virulence, they are eliminated via ingestion by worms </li></ul><ul><li>Created strains of genetically altered bacteria </li></ul>
    10. 10. Flight Studies <ul><ul><ul><li>STS-123, 124, 126: </li></ul></ul></ul><ul><ul><ul><ul><li>Enhanced Salmonella virulence </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Gene target identification </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Vaccine development strategy </li></ul></ul></ul></ul><ul><ul><ul><li>STS-119, 125: </li></ul></ul></ul><ul><ul><ul><ul><li>Survey flight for virulence </li></ul></ul></ul></ul><ul><ul><ul><ul><li>New organisms </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Use of Salmonella as positive control </li></ul></ul></ul></ul>Taking advantage of the changes in biological processes that occur in microgravity to create new treatments for disease
    11. 11. <ul><li>Microbes flown: </li></ul><ul><ul><li>Methicillin resistant Staphylococcus aureus (MRSA) </li></ul></ul><ul><ul><li>Listeria monocytogenes </li></ul></ul><ul><ul><li>Pseudomonas aeruginosa </li></ul></ul><ul><ul><li>Klebsiella pneumoniae </li></ul></ul><ul><ul><li>Streptococcus pneumoniae </li></ul></ul><ul><ul><li>Proteus mirabilis </li></ul></ul><ul><ul><li>Enterococcus faecalis </li></ul></ul><ul><ul><li>Candida albicans </li></ul></ul><ul><li>Current focus: </li></ul><ul><ul><li>MRSA </li></ul></ul>
    12. 12. <ul><li>Findings made in space are the product of fundamental research. </li></ul><ul><li>The science has facilitated development of a privately held venture. </li></ul><ul><li>Eight successful spaceflight payloads have been conducted ~ two years with industry support. </li></ul><ul><li>Initial work focused on analysis and definition of virulence targets for Salmonella . </li></ul><ul><li>Work with additional microbes is ongoing, with a current focus on MRSA. </li></ul>Pathfinder Progress
    13. 13. How can using space change drug development on earth? <ul><li>The R&D pipeline for a single agent may take years of work to allow identification of good candidates for pharmaceutical applications. </li></ul><ul><li>At the end of this period, the possibility exists that the candidate agent is not suitable for continued development. </li></ul><ul><li>The resources expended getting to this point could be potentially minimized by using a process which identifies promising agents/drug candidates earlier in the development pipeline and allows for quicker testing to evaluate downstream efficacy and market potential. </li></ul><ul><li>Using space, years could be eliminated from R&D pipeline activities, to allow fast-tracking of promising agents and termination of unsuccessful agents at earlier time points . </li></ul>
    14. 14. Using Space to Develop Products for Earth <ul><li>Commercial vaccine </li></ul><ul><li>New therapies </li></ul>+ = Virulence Gene Deletion Flight testing IND
    15. 15. <ul><li>John Phillips working with the experiment. </li></ul><ul><li>The canister houses 8 individual test tubes, each containing replicates of the different organisms. </li></ul>http:// =n57djMwDZAs