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Experiment Overview


Information provided courtesy of the Erasmus Experiment Archive.
Brief Summary

The Mechanisms and Functional Consequences of Protein Kinase C Isoform Translocation in Monocytes Exposed to Microgravity (PKinase) experiment investigates the effects of microgravity on the maturation process of monocytes (infection fighting white blood cells) into macrophages. Macrophages (mature white blood cells) are key to fighting off infection during space exploration.

Principal Investigator(s)

Millie Hughes-Fulford, Ph.D., University of California, San Francisco, CA, United States

Co-Investigator(s)/Collaborator(s)

Augusto Cogoli, Ph.D., Zero-g Tec GmbH, Zurich, Switzerland

Isabelle Walther, Ph.D., Swiss Federal Institute of Technology, Space Biology, Zurich, Switzerland

Developer(s)

Swiss Federal Institute of Technology, Space Biology, Zurich, , Switzerland

Sponsoring Space Agency

European Space Agency (ESA)

Sponsoring Organization

Information Pending

Research Benefits

Information Pending

ISS Expedition Duration

October 2007 - April 2008

Expeditions Assigned

16

Previous ISS Missions

ISS Expedition 16 is the first mission for PKinase.

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Experiment Description

Research Overview

• Mechanisms and Functional Consequences of Protein Kinase C Isoform Translocation in Monocytes Exposed to Microgravity (PKinase) studies crewmember altered immune function during and following space flight.



• Determining the effects of gravity on monocyte differentiation (becoming more specialized) may mitigate immunosuppression.



• PKinase strives to determine the effect of microgravity on Protein Kinase C (PKC) regulated genes that control monocyte differentiation (process by which a less specialized cell becomes more specialized), and the initiation of apoptosis (cell death) and cell cycle arrest, to fully characterize the effect of microgravity on the activation of PKC, and to evaluate downstream signaling of PKC in response to mitogenic (involving cell division) stimulation.

Description

Apollo Astronauts, in 15 of 29 Moon Missions, experienced an infection during or immediately after flight. The T-cell and the monocyte are the two immune cells that exhibit altered function in Shuttle crewmembers. Previous experiments show a decrease in monocytes and macrophages in returning crewmembers. Mechanisms and Functional Consequences of Protein Kinase C Isoform Translocation in Monocytes Exposed to Microgravity (PKinase) hypothesizes that microgravity inhibits the maturation of the monocyte into a macrophage. PKinase tests the ability of microgravity to slow macrophage development by stimulating maturation of the monocyte in microgravity and examining resulting adhesion and gene expression as compared to 1g controls.

These experiments determine if gravity is a factor in macrophage formation and in altering normal signal transduction and gene expression of monocytes. PKinase enables investigators to determine the key regulatory steps in macrophage formation, and if gravity is required for macrophage development.

PKinase seeks to characterize the effect of microgravity on the activation of key Protein Kinase C (PKC) isoforms (different forms of same protein), spatial distribution or redistribution of PKC isoforms within the cell, and signaling downstream of PKC in response to mitogenic stimulation (regulates various cellular activities). Pkinase also examines the effect of microgravity on PKC regulated genes which control monocyte differentiation (process by which a less specialized cell becomes more specialized).

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Applications

Space Applications

PKinase helps scientists understand the immunosuppression that occurs during space flight and can facilitate the development of preventive and corrective measures for long duration missions.

Earth Applications

Since all terrestrial life began in a gravity field, this study examines alterations of early T-cell activation, whereby microgravity gives us the unique opportunity to examine the role of Earth's gravity in immune function. The PKinase study shows the regulation of the earliest signals that cause the T-cell to activate and the role of normal Earth's gravity in that signaling.

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Operations

Operational Requirements

Cells are placed into the Kubik incubator upon their arrival. The cells are then removed from the Kubik incubator, and activated after three hours. Cells are then placed back into the Kubik incubator.

Operational Protocols

Cells are grown in floating piston hardware made by Kaiser Italia. Prior to the launch of the Soyuz, cells are placed into the hardware.

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Results/More Information

Information Pending

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Results Publications

Chang TT, Walther I, Li C, Boonyaratanakornkit JB, Galleri G, Meloni MA, Pippia P, Cogoli A, Hughes-Fulford M.  The Rel/NF-?B pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity. Journal of Leukocyte Biology. 2012; 92(6): 1133-1145. DOI: 10.1189/jlb.0312157. PMID: 22750545.

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Ground Based Results Publications

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ISS Patents

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Related Publications

Hughes-Fulford M, Rodenacker K, Jutting U.  Reduction of anabolic signals and alteration of osteoblast nuclear morphology in microgravity. Cellular Biochemistry. 2006; 99: 435-449. DOI: 10.1002/jcb.20883.


Hatton JP, Gaubert F, Cazenave J, Schmitt D.  Microgravity modifies protein kinase C isoform translocation in the human monocytic cell line U937 and human peripheral blood T-cells. Journal of Cellular Biochemistry. 2002; 87(1): 39-50.

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Related Websites

Laboratory of Cell Growth

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Imagery

Monocyte differentiation in normal gravity. Image courtesy of Ames Research Center.
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PKinase inside the transportable Kubik incubator.
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Soyuz Commander Yuri Malenchenko manipulates the Kubik incubator inside the Russian segment of the ISS.
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