Scientists strive to determine the structure and function of proteins to better understand the studies of medicine, agriculture, the environment and other biosciences. Why? It is because every chemical reaction essential to life depends on the function of protein structures.
The three-dimensional structure of protein crystals is studied to determine how structure affects the function of individual proteins. Scientists want to understand how proteins work, how to build them from scratch, or how to improve them.
To conduct this type of study, scientists must first generate crystals that are large enough and uniform enough to provide useful structural information upon analysis. Protein crystals grown in microgravity -- the near weightlessness experienced on a spacecraft in orbit -- are often significantly larger and of better quality than those grown on Earth.
The Advanced Protein Crystallization Facility (APCF) is designed to develop difficult-to-produce, biologically important protein crystals for analysis, and to study different methods of protein crystal growth. It is sponsored by the European Space Agency as part of the International Space Station's Expedition Three science experiments.
Previous experiments on the Space Shuttle and Mir have shown that microgravity-grown crystals often provide better structural data than their ground-grown counterparts. Since many of the proteins that interest medical researchers have not produced crystals of adequate size and quality on Earth, microgravity-grown crystals on the International Space Station is the next step.
On the ground, once a high-quality crystal has been selected, it is examined through a process called X-ray diffraction, in which X-rays are directed into the crystal and are scattered in a regular manner by the atoms in the crystal. The scattered X-rays are recorded on photographic film or electron counters. This data are then fed into a computer, which can perform precise measurements of the intensity of the X-rays scattered by each crystal, helping scientists to map the probable positions of the atoms within each protein molecule.
The crystals obtained during Expedition Three will be used in structure determination as part of the commercial development of the space program.
During the past 12 years, several hardware configurations have been used to conduct protein crystal growth experiments on Space Shuttle flights.
The Advanced Protein Crystallization Facility was developed to support three types of protein crystal growth methods: liquid-liquid diffusion, vapor diffusion, and dialysis. On this flight the liquid-liquid diffusion will not be implemented. The computer-controlled facility will be placed in EXPRESS Rack 1 in the US Destiny laboratory module.
Each APCF unit is capable of accommodating 48 modular protein crystal growth chambers, or reactors, of which 10 can be observed by a high-resolution video camera. Images from the video camera will make it possible for investigators to study crystal growth development. A Mach-Zender interferometer in the APCF will allow observation of five of the 48 cells and measure and visualize changes in the refractive index due to concentration gradients, diffusion or convection.
The hardware consists of a process chamber, power and data electronics, the camera electronics, optical and video system, thermal control system, and tape recorder. The APCF is designed to run automatically, but the crew can verify the status of the facility by reading the LEDs mounted on the front panel.
The facility's process chamber is maintained at 20 degrees Celsius (68 degrees Fahrenheit). Temperature data are recorded during the whole mission.
The optical system is mounted on a drive to enable a direct observation of the protein chamber, 10 reactors in a sequence, five on each side. Five reactors will be observed with a wide field of view. Five will be observed with a narrow field of view. Five of the reactors can also be viewed in interferometer mode. Direct observation can also be made under light-emitting diode (LED) illumination with polarized light.
Images are acquired through a black and white camera, digitized and stored on the tape recorder.
The reactors are activated after transfer to the EXPRESS Rack by rotating the central cylinder by 90 degrees so as to bring the intermediate solution into contact with the solutions in the two neighboring chambers.
Of the two processing methods used on this flight, the first one, vapor diffusion, allows crystals to form inside a drop of protein solution, The second one, dialysis separates the protein and salt solutions by a membrane.
The Advanced Protein Crystallization Facility has been used on five prior missions, including Spacelab-1 in June 1993, International Microgravity Lab-2 in July 1994, United States Microgravity Lab-2 in October 1995, Life and Microgravity Spacelab in June 1996 and STS-95 in October 1998. More than 20 scientific papers have been based upon the 426 previous experiments.
On this flight, eight separate investigators will use the unit to study a wide variety of proteins.
Proteins are important, complex biochemicals that serve a variety of purposes in living organisms. Metabolic processes involving proteins play an essential role in our lives, from providing nourishment to fighting disease. In the past decade, rapid growth in protein pharmaceutical use has resulted in the successful application of proteins to insulin, interferons, human growth hormone, and tissue plasminogen activator.
The pharmaceutical industry is interested in getting high-quality crystals to determine the structure of target proteins and help with the rational design of new drugs. Other potential applications include agricultural products and bioprocesses for use in manufacturing and waste management.
Structural information gained from protein crystal growth (PCG) activities can provide a better understanding of the body's immune system and aid in the design of safe and effective treatments for disease and infections.
More information on this facility and other experiments are available at: