Fungal Pathogenesis, Tumorigenesis, and Effects of Host Immunity in Space (FIT) - 06.01.16

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

ISS Science for Everyone

Science Objectives for Everyone
The Fungal Pathogenesis, Tumorigenesis, and Effects of Host Immunity in Space (FIT) experiment primarily studies the effects of spaceflight on the immune system responses of the fruit fly, Drosophila melanogaster. Since there is evidence that suggests the immune system of organisms are affected by spaceflight, this proposal seeks to assess the extent and the detailed molecular biological changes that are associated with spaceflight. In addition, this work also investigates the progression of cancerous and benign tumors in sensitized mutant lines (cells that turn into tumors) that show an increase in tumor formation, and is coupled with the effect of radiation exposure.
Science Results for Everyone
Space makes human immune systems less fit. This investigation looked at how it does this using a well-established research stand-in for humans - the fruit fly. Data show that short-term space flight changed gene expression and affected fundamental immune processes and maturing of immune cells. After space flight, a specific defense pathway activated by Gram-negative bacteria performed normally, but a different defense pathway stimulated by Gram-positive bacterial infections showed dysfunction. Exposure to hypergravity, however, improved the Gram-positive pathway. This indicates that hyper- and microgravity have the opposite effect on infection defense mechanisms. Further research helps to further understand and counteract these effects.

The following content was provided by Sharmila Bhattacharya, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: FIT

Principal Investigator(s)
Sharmila Bhattacharya, Ph.D., NASA Ames Research Center, Moffett Field, CA, United States

Co-Investigator(s)/Collaborator(s)
Deborah A. Kimbrell, Ph.D., University of California, Davis, CA, United States

Developer(s)
NASA Ames Research Center, Moffett Field, CA, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)

Research Benefits
Information Pending

ISS Expedition Duration 1
April 2006 - September 2006

Expeditions Assigned
13

Previous Missions
This will be the first flight for the FIT experiment.

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Experiment Description

Research Overview

  • Fungal Pathogenesis, Tumorigenesis, and Effects of Host Immunity in Space (FIT) will provide detailed information on the interaction between elements of the space environment on immune function.
  • FIT also investigates the growth of cancerous and benign tumors in sensitized genetic lines (breeds) of Drosophila melanogaster (fruit flies) that show an increase in the incidence of tumor formation. The effect of ground radiation exposure is coupled to this study.
  • In addition, samples of a fungal pathogen that infects flies are exposed to the space environment. Space-flown samples are used postflight to infect fruit flies on the ground and assess changes in the pathogen.

Description

The Fungal Pathogenesis, Tumorigenesis, and Effects of Host Immunity in Space (FIT) investigation takes place on board the Space Shuttle during the STS-121/ULF1.1 mission. FIT addresses a series of health risks associated with space flight using Drosophila melanogaster (fruit flies) as a simple model organism that can be flown on the shuttle with minimal resources and with large samples sizes. The innate immunity is the first line of defense that multicellular organisms, such as humans and flies (Drosophila melanogaster), use when faced with pathogens. These responses include expression of antimicrobial peptides, phagocytosis of the microbes by blood cells and clotting/melanization. All of these responses will be measured from animals returning from space flight and compared to ground-bred animals. A fungal pathogen will also be flown in order to assess whether space flight results in changes in virulence in the fungus. Ground radiation studies with high energy protons, as experienced by astronauts during solar flares, will be used to assess the effects of radiation on the immune system as well as on tumor formation in the fly. The use of Drosophila melanogaster (fruit fly) to study immunity allows for large population sizes of animals to be studied in relatively small volumes, yielding statistically significant data.

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Applications

Space Applications
It is a known fact that space travel affects the genetic activity of crewmembers, but researchers cannot yet predict which genes will be affected or precisely determine how gravity signals a gene to change. FIT is the first step in answering these questions.

Earth Applications
Effects of pathogens on wild type and immune-compromised hosts is of great relevance to human immune diseases.

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Operations

Operational Requirements and Protocols

In flight, the crew conducts one session of the food tray change-out operation. At the time of the food tray change-out, the food tray exposed to the adult flies carries eggs, embryo, and larvae. The procedure consists of transferring a new food tray into the fly cassette that carries the adult flies and then transferring the food tray with the larvae into a new unused fly cassette. The Platform Kit is used to provide containment during this operation. Postflight, the specimens are returned for processing by the PI team.
 
The flies are housed in cassettes that are modified from ESA type 1 containers and have been rebuilt at NASA Ames in order to ensure no escape of larvae, and for efficient food change-out in space using the Platform Kit also designed at NASA Ames for the FIT experiment.
 
 

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Space travel weakens the immune system, making humans vulnerable to opportunistic infections and immune related illnesses. The FIT experiment studied the effects of spaceflight, and hypergravity, on the immune responses of the common fruit fly, Drosophila melanogaster, since it is a well-established model similar to human in innate immune function (first line of defense against invading microorganisms), cellular and humoral immunity, clotting and wound healing, and defense signaling pathway. The large number of fruit flies returned from FIT allowed a significant number of biochemical analyses to be performed on flies that developed to adulthood in microgravity. Focusing on both bacterial and fungal infections, researchers found that space flies subsequently infected by fungus failed to respond. This suggests that the Toll defense pathway in Drosophila, stimulated primarily by fungal and Gram-positive bacterial infections, is dysfunctional in adult space flies rendering them severely immunocompromised. However, improved resistance to Toll-mediated fungal infections is found in flies exposed to hypergravity. In contrast, infecting space flies with bacteria produced normal activation of the Immune Deficiency (IMD) pathway, activated mainly by Gram-negative bacteria. Space-flown larvae showed defects in the efficiency of phagocytosis by hemocytes, and the expression of several genes relating to humoral immunity, hemocyte maturation and pathogen recognition were down regulated. The major findings of the study are that hypergravity and spaceflight have opposing effects, and that spaceflight produces stress-related negative immune responses and results in a specific inability to mount a Toll-mediated infection defense. Continued research is needed to understand these issues better and to contribute to the design of effective countermeasures.

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Results Publications

    Taylor K, Kleinhesselink K, George MD, Morgan R, Smallwood T, Hammonds AS, Fuller PM, Saelao P, Alley J, Gibbs AG, Hoshizaki DK, von Kalm L, Fuller CA, Beckingham KM, Kimbrell DA.  Toll mediated infection response is altered by gravity and spaceflight in Drosophila. PLOS ONE. 2014 January 24; 9(1): e86485. DOI: 10.1371/journal.pone.0086485.

    Marcu O, Lera MP, Sanchez ME, Levic E, Higgins LA, Shmygelska A, Fahlen TF, Nichol H, Bhattacharya S.  Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight. PLOS ONE. 2011; 6(1): 1-10. DOI: 10.1371/journal.pone.0015361.

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Ground Based Results Publications

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ISS Patents

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Related Publications

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Related Websites
Science@NASA
CNN.com - Humans, 'golden bug' share many traits
NASA Sends Flies into Space to Test Changes in Immune System

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Imagery

image Dr. Sharmila Bhattacharya, prinicpal investigator, checks the health of the fly culture in readiness for the shuttle flight experiment. Image courtesy of Ames Research Center.
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image Matthew Lera, a research scientist at Ames Research Center, preparing media for maintaining fly stocks that will be used for the shuttle experiment. Image courtesy of Ames Research Center.
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image Drs. Oana Marcu and Laura Higgins, research scientists at Ames Research Center, conduct immunity assays in preparation for the launch of the Space Shuttle experiment. Image courtesy of Ames Research Center.
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image Replenishing the flies with new food to generate the next generation of flies in space. Image courtesy of Ames Research Center.
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image Fly hemocytes (blood cells) engulfing bacteria as a way of resisting infection. Image courtesy of Ames Research Center.
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image Drosophila melanogaster(fruit flies). Image courtesy of Ames Research Center.
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