NASA - National Aeronautics and Space Administration

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Experiment Overview


Brief Summary

Proteins are important macromolecules without which our bodies would be unable to repair, regulate, or protect themselves. The use of X-ray crystallography to determine protein structure requires the production of well-ordered protein crystals that are of sufficient quality. Without high quality crystals of a protein, it is impossible to carry out crystallographic structural studies. Using three-dimensional structure information, researchers can determine how proteins function and in cases where these proteins are involved in disease processes, the structure is often used to design new drugs that specifically interact with the protein. Many leading drugs today are the product of structure-based drug design. Crystal growth in a microgravity environment can have beneficial effects on the size and more importantly, the intrinsic order of these protein crystals.

Principal Investigator(s)

Lawrence J. DeLucas, Ph.D., O.D., University of Alabama at Birmingham, Birmingham, AL, United States

Co-Investigator(s)/Collaborator(s)

Alexander McPherson, Ph.D., University of California, Irvine, Irvine, CA, United States

Developer(s)

University of Alabama, Birmingham, Birmingham, AL, United States

Sponsoring Space Agency

National Aeronautics and Space Administration (NASA)

Sponsoring Organization

National Laboratory (NL)

Research Benefits

Information Pending

ISS Expedition Duration:

September 2013 - September 2014

Expeditions Assigned

37/38,39/40

Previous ISS Missions

HDPCG trays flew installed in a Commercial Refrigerator Incubator Module (CRIM) during Expeditions 2 and 4. PCG Straws flew installed in a Sample Transfer Container (STC) during Russian Soyuz flights TMA-13 and TMA-16. MERLIN hardware that will support the CPCG-HM experiment has operated continuously on ISS since Nov 2008.

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Experiment Description

Research Overview

• To conclusively demonstrate the effect of microgravity on the size and quality of crystals for a variety of high-value proteins.



• Upon completion for the experiments it will be demonstrated that microgravity protein crystallization provided an improvement over ground controlled crystallization.



• Improved space grown protein crystals will provide three-dimensional x-ray crystallographic structures for several high valued proteins. Eventually these structures will help researchers determine how specific proteins function and are involved in the disease process. Numerous drugs today are the product of this structured based drug design.

Description

Proteins are important macromolecules without which our bodies would be unable to repair, regulate, or protect themselves. The use of X-ray crystallography to determine protein structure requires the production of well-ordered protein crystals that are of sufficient quality. Without high quality crystals of a protein, it is impossible to carry out crystallographic structural studies. Using three-dimensional structure information, researchers can determine how proteins function and in cases where these proteins are involved in disease processes, the structure is often used to design new drugs that specifically interact with the protein. Many leading drugs today are the product of structure-based drug design. While enormous strides have been made in the last decade, there remain a large number of important proteins where the difficulty of obtaining high-quality crystals is the chief barrier to their structural analysis. One class of proteins, membrane proteins, comprises a number of targets identified by the pharmaceutical industry as high-value commercial opportunities (membrane proteins were the targets for approximately 67% of all past marketed drugs and it is estimated that they will comprise targets for an equal percentage of all future drugs)[1]. Membrane protein crystallization represents one area where the onset of space commercialization can maximize the impact of the microgravity environment in space-based research applications for the academic, government and pharmaceutical industry. Other areas include high-value aqueous proteins and protein complexes (based on their functional importance in biological systems) many of which have yielded crystals of poor quality (thus far microgravity crystallization has been attempted on only 3 membrane proteins and two protein complexes). Access to unique data optimized in microgravity could have great relevance for understanding protein structures and advancing new drugs into the pharmaceutical market. Crystal growth in a microgravity environment can have beneficial effects on the size and more importantly, the intrinsic order of these protein crystals. Membrane proteins and large aqueous proteins or protein complexes typically diffract poorly and exhibit high mosaicity. Significant disadvantages of past microgravity flights include the short mission duration (the majority of the past data was collected on spatial flights with mission durations of two weeks or less). The results of the program, while intriguing, had a limited impact on structural biology during a time when technological innovations on the ground have produced significant and fundamental advances in our understanding of protein function. However, despite the increased sophistication of ground-based protein crystallization projects, the crystals of a large number of important targets today still have suboptimal diffraction characteristics. Even a slight improvement in diffraction data would have a significant impact on scientist?s ability to use the resulting structures to provide important insights into biological mechanisms.

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Applications

Space Applications

n/a

Earth Applications

Provide important insights into biological mechanisms. Develop new drugs based on protein crystal structures.

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Operations

Operational Requirements

Temperature controlled between 4C and 22C. Continuous powered required from pre-launch through post-landing. Late access and early retrieval are required.

Operational Protocols

Pending selections.

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Results/More Information

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Related Websites

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Imagery

CPCG-HM Design ? Illustration depicts the MERLIN Assembly with 2 HDPCG trays and STC tray that will hold the liquid-to-liquid sample straws. Image courtesy of University of Alabama.
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CPCG-HM Design ? Illustration the CPCG-HM Assembly with 4 HDPCG trays. Image courtesy of University of Alabama.
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CPCG-HM Design ? Vapor Diffusion Sample Blocks configuration from Launch to Landing. Image courtesy of University Alabama.
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CPCG-HM Design ? Crystal formation inside Vapor Diffusion Sample Block. Image courtesy of University of Alabama.
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