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Fact sheet number: FS-2001-11-186-MSFC
Release date: 11/01


Commercial Protein Crystal Growth-
High Density (CPCG-H)


Missions: Expedition Four, ISS Mission 8A, STS-110 for March 21, 2002; experiment will continue through Mission UF-2, STS-111 for May 2, 2002

Experiment Location on ISS: U.S. Lab EXPRESS Rack 4

Principal Investigator: Dr. Lawrence DeLucas, Director, Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham

Project Manager: John West, NASA Space Product Development Program, Marshall Space Flight Center, Huntsville, Ala.


Overview

The word "protein" is coined from the Greek proteios, or "primary." Proteins are the primary building blocks of all life, and how they react with other biochemical compounds in living organisms determines many things, including if a creature will be healthy or become ill. First discovered in 1838, proteins are recognized as the predominant ingredients of cells. Understanding this hidden world is intensely interesting and important to scientists and physicians.

Each protein has a particular chemical structure, which means it has a favored "shape." Researchers still lack detailed knowledge about the structures of many proteins. If they can determine the shape, or shapes, of a protein, they can learn how it works. Once this is understood, researchers can then find a way to help or hinder a given protein, and they may be able to develop new treatments that target specific human, animal and plant diseases.

One of the most widely used methods of studying protein structures is protein crystallography. Proteins can be made to crystallize in much the same way sugar crystals can be formed from sugar water to make rock candy. Scientists then use x-rays to determine the three-dimensional molecular structures of proteins.

The structures of many important proteins remain a mystery simply because researchers are unable to obtain crystals that have the quality or size required for x-ray crystallographic studies. NASA 's Protein Crystal Growth (PCG) program has been developed to learn how protein crystals grow in space and how to optimize the growth process, while producing large, high-quality crystals of selected proteins. The near-zero microgravity conditions inside an orbiting spacecraft allow crystals to grow in a more regular and perfect form because of the effects of convection and sedimentation are dampened relative to the 1-g laboratory.

The Commercial Protein Crystal Growth - High Density (CPCG-H) experiments, developed by the Center for Biophysical Sciences and Engineering at the University of Alabama at Birmingham, will launch on Space Shuttle flight STS-110, scheduled for launch in March 2002 as part of ISS mission 8A, and be transferred to the International Space Station. Researchers hope that these experiments will provide large, well-ordered protein crystals of several different proteins for X-ray analysis that will lead to the development of new drugs. The experiment is scheduled to return to Earth onboard the Shuttle STS-111 mission in May 2002.

Experiment Summary

The Commercial Protein Crystal Growth-H experiment consists of 1,008 individual experiments contained in a High-Density Protein Crystal Growth Assembly. This assembly is then stored in the Commercial Refrigerator Incubator Module (CRIM) at 22 degrees Celsius (72 degrees Fahrenheit).

The Space Station crew will install the CRIM into a locker in the Space Station EXPRESS Rack 4 in the U.S. Lab, activate the crystal growth experiments and conduct daily status checks. These daily checks consist of checking temperature readings and cleaning the air filter. When the payload is scheduled to return to Earth, the crew will deactivate the experiments and return the module.

The protein crystals will be grown using a process known as vapor diffusion. Each experiment chamber consists of a small chamber that holds the protein crystal solution and a reservoir chamber that holds the precipitating agent solution. A small droplet of protein solution is mixed with a small amount of precipitating agent solution and placed in the protein chamber.

During activation, the protein chamber is rotated so it is in vapor contact with the reservoir. Water molecules migrate from the protein droplet through the vapor space into the more concentrated reservoir. As the volume of the protein droplet decreases, the concentration of protein increases and protein crystals form. As the experiment continues, the crystals grow larger.

Once back on Earth, the crystals will be studied using a process called X--ray diffraction. Scientists send a beam of X-rays through the crystal and measure how the atoms in the crystal scatter the X-rays. By studying the pattern made by the X-rays, scientists can map the locations of the different atoms, allowing them to create a 3-dimensional model of the protein. With this structural information, researchers determine how the protein functions and can design small molecules to aid or impede the protein's function. This process, known as structure-based drug design, may lead to more effective drugs that target specific proteins.

Background/Flight History

Because of the enormous potential this research offers, the Center for Biophysical Sciences and Engineering (formerly the Center for Macromolecular Crystallography or CMC), a NASA-sponsored Commercial Space Center located at the University of Alabama at Birmingham, has more than 50 major industry and academic partners using the low-gravity environment of space to grow protein crystals for use in drug design.

Protein-crystal growth experiments began flying on the Space Shuttle in 1985. Today, more than 40 protein-crystal growth payloads have flown, producing diffraction-quality crystals of many proteins. The CPCG-H first flew aboard the ISS during Expedition Two, launching aboard STS 100 in April 2001 and returning aboard STS 105 in August 2001. The data derived from each crystal analyzed is leading researchers closer understanding the structure and function of proteins.

Benefits

NASA's commercial research program attempts to use the materials or knowledge developed in space to develop or improve a commercial product or service on Earth. Commercial space research has the potential to create new or improved products, create jobs, give United States industry competitive advantages and improve the quality of life on Earth.

Structural studies using microgravity-grown protein crystals may provide information that can be used in the development of new drugs. With the advent of genetic information from humans and many other species, the role proteins play in diseases and degenerative conditions is becoming more clear and the need for information about the structure of these proteins more critical.

Experiments involving the crystallization of proteins and other biological macromolecules will be part of the ongoing research conducted aboard the International Space Station. The Space Station provides an ideal platform for growing crystals that require longer periods of microgravity than has been available on short duration Space Shuttle flights.

Benefits from protein growth experiments conducted in space have already been seen. Many of the crystallization experiments conducted on the Space Shuttle have yielded crystals that furthered structural biology projects. For example, microgravity crystallization experiments have been conducted with recombinant human insulin. These studies have yielded X-ray diffraction data that helped scientists to determine higher-resolution structures of insulin formulations. This structural information is valuable for ongoing research toward more effective treatment of diabetes.

Other very successful microgravity crystallization experiments have provided enhanced X-ray diffraction data on a protein involved in the human immune system. These studies have contributed to the search for drugs to decrease inflammation problems associated with open-heart surgery. The crystallization of proteins in the low-gravity environment of Earth orbit has developed into a valuable and necessary tool for the science of macromolecular crystallography.

Crystallization experiments conducted on the International Space Station, involve not only human but also animal and plant proteins, and promise to help answer key questions about the world around us.

More Information

More information on this experiment and other experiments are available at:

http://www.scipoc.msfc.nasa.gov/
http://www.spaceflight.nasa.gov/
http://www.microgravity.nasa.gov/
http://www.spd.nasa.gov/
http://spaceresearch.nasa.gov/
http://commercial.nasa.gov/
http://www.cbse.uab.edu/


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