Influence of microgravity on the production of Aspergillus secondary metabolites (IMPAS) – a novel drug discovery approach with potential benefits to astronauts’ health (Micro-10) - 06.01.16

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
The stressful environment of space causes changes to all forms of life, from bacteria and fungi, to animals and people. The Influence of microgravity on the production of Aspergillus secondary metabolites (IMPAS) – a novel drug discovery approach with potential benefits to astronauts’ health (Micro-10) investigation studies how the stress of microgravity triggers changes in growth, gene expression, physical responses, and metabolism of a fungus called Aspergillus nidulans (A. nidulans), an important biomedical research species. Results provide new data on how spaceflight affects fungi, including whether the fungi can be induced to make new molecular compounds that could be used for development of new drugs.
Science Results for Everyone
Information Pending

The following content was provided by Stefanie Countryman, M.B.A., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Micro-10

Principal Investigator(s)
Clay Wang, Ph.D., USC School of Pharmacy, Los Angeles, CA, United States

Co-Investigator(s)/Collaborator(s)
Information Pending

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

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
NASA Research Office - Space Life and Physical Sciences (NASA Research-SLPS)

Research Benefits
Earth Benefits, Scientific Discovery, Space Exploration

ISS Expedition Duration 1
March 2016 - September 2016

Expeditions Assigned
47/48

Previous Missions
Information Pending

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Experiment Description

Research Overview

In the Influence of microgravity on the production of Aspergillus secondary metabolites (IMPAS) – a novel drug discovery approach with potential benefits to astronauts’ health (Micro-10) flight experiment, fungal samples are grown and optimized for flight in hardware provided by BioServe. Approximately 3 days before launch, spores of the fungi (1 x 107 spores per sample) are aseptically (free from pathogens) spotted on yeast agar glucose (YAG) solid media in Omnitray plates. A total of six Omnitray plates are placed in each Plate Habitat (PHAB), a temperature conducting containment device for the experiment. PHABs are incubated inside a Space Automated Bioproduct Laboratory (SABL) on the International Space Station (ISS).
 
Samples are stored at 4°C during transport and “activated” and grown at 37°C once on board ISS in the SABL. Two separate SABLs (each containing 4 PHABs with 6 sample Omnitray plates) are used to establish a time course for the experiment; one time point is 4 days, and other 7 days. All samples are “terminated” by cooling to 4°C once the time point is reached. Samples are transported back to Earth at 4°C and returned to Principal Investigator’s lab as soon as possible. The experiment can be entirely performed merely by modulating the temperature of the cultures within the PHABs. Fungal cells remain viable for many weeks dormant at 4°C.
 
Ground controls are produced separately once data from SABL flight conditions (e.g., temperature change rates) are obtained.
 
From each flight experiment time point (4-days and 7-days), half of the samples are processed immediately upon return to Earth, and the other half are used to regrow the ISS-generated fungal cells under Earth-normal conditions. Metabolomic, proteomic and genomic/transcriptomic analyses are performed, with final “omics” data archived in NASA GeneLab.

Description

Filamentous fungi are abundant and essential in nature, providing ecosystem balance and critical roles in the chemical cycling. The production of secondary metabolites – compounds that provide a selective advantage to fungi but are not essential for growth or reproduction – can be exploited by humans to make beneficial pharmaceuticals. Many secondary metabolites are stimulated (naturally or artificially) by environmental cues, including stress conditions. Despite recent advances in the field, it is thought that many secondary metabolite pathways remain hidden. The overarching objective of the Influence of microgravity on the production of Aspergillus secondary metabolites (IMPAS) – a novel drug discovery approach with potential benefits to astronauts’ health (Micro-10) flight experiment is to test if microgravity allows silent fungal metabolite pathways to become activated. Microgravity might generate a unique stress not achievable with ground-based cell culture studies. The research team studies the effects of microgravity on the production of fungal metabolites, and tests the hypothesis that spaceflight alters fungal gene expression, protein production, and overall physiological responses.
 
The fungal species to be flown is a model organism in the field of fungal-based pharmacology. Its genome has been sequenced and its regulatory machinery is relatively well understood, thus enabling a variety of modern, “omics”-based analyses by the research team. A wildtype strain and three different mutant strains are flown, each targeting pathways potentially triggered by microgravity. A deeper understanding of how spaceflight influences filamentous fungal growth characteristics, gene expression, and secondary metabolite production could emerge from the flight experiment, with far-reaching pharmaceutical applications. Moreover, future research teams will have access to space-flown fungal cells and data archived in GeneLab is to be accessible to the scientific community for examining novel secondary metabolite pathways.

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Applications

Space Applications
This investigation compares the molecular profiles of space-flown fungi with controls grown on Earth, enabling researchers to understand how the spaceflight environment affects fungal growth. In previous research in stressful conditions, the fungus in this investigation has produced compounds that help treat osteoporosis, or low bone density, which is a problem that affects crew members living in orbit. Results from this investigation benefit efforts to produce new pharmaceutical compounds in space.

Earth Applications
Fungi are relatively easy to grow in environments with limited access to nutrients and water, and they can provide a good source of protein, as well as a basis for new medicines. Penicillin, one of the most important medicines in history, is derived from fungi. Like plants, bacteria, and animals, fungi grow differently when exposed to the harsh environment of space, but microgravity’s effects on fungi are not well understood. This investigation studies strains of a well-known fungus to determine whether they produce new molecular compounds in space. Any new biomolecules derived from fungi could have major benefits for pharmaceutical research, potentially leading to new treatments and drugs for a wide range of ailments.

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Operations

Operational Requirements and Protocols

The experiment must be transported to the ISS under thermal control at 4°C. The experiment requires thermal control at 37°C while active on board the ISS, and inside of SABL. The samples must be maintained at 4°C once the experiment is terminated, and held at 4°C until they are returned to Earth.

Hardware with samples is transported to ISS under thermal control. Once the experiment reaches the ISS, the crew transfers the experiment from the cargo vehicle to the SABL unit that resides in the Expedite the Processing of Experiments to the Space Station (EXPRESS) rack on board the ISS. SABL holds the samples at 4°C until activation. SABL is commanded to 37°C for activation, and then commanded to 4°C for termination and stowage until return to Earth.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites

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Imagery