Point Source (Southampton, England) reported the use of a novel laser fiberoptics delivery technology for fundamental research into microgravity protein crystallization, conducted in space during NASA space shuttle missions. The goal of these studies is to grow high-quality protein crystals, which may be used to help determine the three-dimensional structure and function of proteins in the human body. The Center for Macromolecular Crystallography (CMC) at the University of Alabama at Birmingham is using the low-gravity environment of space to grow protein crystals for use in drug design. The experiments are conducted in space because protein molecules used in the studies grow better under microgravity.
The CMC is pioneering the technique, dynamically controlled protein crystal growth, for studying protein crystal growth in both terrestrial and microgravity environments. The crystal growth process begins from supersaturated aqueous solutions in which protein aggregation takes place, followed by nucleation and subsequent crystal growth. Supersaturation, and hence growth, is controlled via solution concentration and temperature. When the process is studied on Earth, results show that the heavier and more complex the crystal is, the more prone it is to have internal defects. Thus, space-based growth is proving to be the best route to obtaining ultrapure samples.
Incorporated recently within the protein crystal growth technique is a laser light-scattering system that detects protein molecule aggregation events, the first step of crystal growth. This aggregation information is then fed back via a fiberoptic delivery system to provide dynamic control of crystal growth. The laser light-scattering system uses a very stable laser diode that provides an output power stable to ±2% over 24 hours.
Larry DeLucas, director of the CMC and Michael Harrington, associate director, head a team that developed the hardware for the protein crystal growth experiments. The CMC experiments have already flown on more than 38 space shuttle missions. Earlier experiments used manual/mechanical systems for monitoring and controlling the protein solution supersaturation but the Point Source technology has enabled the CMC team to conduct noninvasive sensing and control.
Protein crystal growth is a recurring Space Shuttle experiment because there are more than 300,000 proteins in the human body and scientists know the structure of less than 1% of them. The CMC has attempted to crystallize hundreds of proteins in space, each with a potential product. Despite relatively good research success, the long time required to get a pharmaceutical to market has allowed only a few potential products to reach clinical trials and the final premarket stages of development.
Proteins ranging from insulin to HIV-Reverse-Transcriptase have been produced in space as larger, purer, and new, never-before-seen crystal structures. Knowledge from these studies may lead to the development of novel, more effective drugs to fight diseases such as cancer, diabetes, alcoholism, AIDS and Alzheimer's disease.
