August 2002

Dr. Edward Snell
Senior Scientist
Laboratory for Structural Biology
Marshall Space Flight Center

Dr. Edward Snell is a Senior Scientist in the Laboratory for Structural Biology at NASA’s Marshall Space Flight Center in Huntsville, AL. As a crystallographer, he is attempting to map the structure of disease-causing proteins.

NASA Tech Briefs: What is the novelty of this particular research?

Dr. Edward Snell: Microgravity offers us an environment that has been shown, through our research and others, to grow crystals that are physically more perfect than those on the ground. We crystallize biological macromolecules that are important in understanding how diseases are caused and how they can be stopped. From X-ray analysis of the crystals and a lot of hard work, we can get a picture of the macromolecule.

Microgravity gives us a better-ordered crystal and results in a clearer picture. In collaboration with Dr. Gloria Borgstahl at the University of Toledo, we have been studying how the better ordering occurs and what physical effects that has on the crystals. We have been looking at insulin and developed new techniques to characterize the microgravity improvements rapidly and statistically. NASA has provided a grant to Dr. Borgstahl for this research, which has provided the seed funding for further investigations into other macromolecules, notably some responsible for cancer.

NTB: How does your role as a crystallographer tie in with this work?

Snell: As a crystallographer, I’m interested in the interaction of X-rays with the crystals. I want to grow the best quality crystal and optimize the data I can get from that crystal by careful design of the experiment and using a powerful synchrotron X-ray source ? an X-ray machine the size of several football fields. I work with Dr. Borgstahl on getting the best X-ray data from the crystals.

NTB: Why is growing crystals on the International Space Station more advantageous than growing crystals on Earth?

Snell: Back in 1981, a sounding rocket was used to grow a protein in microgravity while it was filmed with a special camera. During the short period of growth, clear differences were seen in the growth from that on the ground. The film showed smooth fluid flow around the crystal compared to turbulent convection on the ground. Our own studies (Dr. Borgstahl and myself) with six microgravity and six ground-grown insulin crystals gave microgravity crystals averaging 34 times larger volume with seven-fold improvement in crystal quality, resulting in improved structural detail. These were grown on the Space Shuttle during John Glenn’s flight ? he activated this particular experiment.

Biological macromolecules have different growth times. We could grow the insulin crystals on the short duration of the Shuttle mission, but many crystal growth experiments need a longer time. The Space Station gives us this time. It also allows the potential for a much more exciting kind of experiment.
At present when we grow crystals in the laboratory, we look at the results and start a new experiment using the knowledge from our observations to optimize the crystals. Our first crystal may not be suitable for X-ray analysis and several iterations may be needed. With the Space Shuttle, you had to wait until it came back, analyze the results, and wait until the next mission. With the long-duration missions of the Space Station, we may be able to do science as we do it in the laboratory. Our experiments are very small; over a hundred could fit in a shoebox. The potential from them is very high depending on the sample being studied.

NTB: What is the novelty of your work with insulin crystals?

Snell: We have been using the insulin crystals to test our new methods and techniques. These include ultra-fine slices through the data and a very parallel, monochromatic synchrotron X-ray beam. This allows us to see far more detail in the data than previously achievable. Our methods also allow us to rapidly look at many samples in a short period of time. We are now applying these methods to other samples.

NTB: What will this research mean for cancer and diabetes research?

Snell: Structural crystallography - what we do - provides the picture of the macromolecule. Once scientists have the picture, they can understand how the macromolecule works and can design a drug to stop or aid its function. A lot of work has gone into improving the quality of life for diabetes patients. The insulin we are studying is part of that work. Work on cancer that Dr. Borgstahl has just been funded for will advance the knowledge of that disease.

With enough knowledge comes the treatment or cure, but we’ll have to wait a while, unfortunately. The whole process from crystal to structure, and maybe a new drug, takes many years. Microgravity crystals giving more details help the process.

NTB: Do you foresee any other applications for microgravity-grown protein crystals?

Snell: The primary application for biological macromolecular crystals is in biomedical research ? understanding the structure to understand how life works and make sure it keeps working. Structural knowledge is used in other areas such as industrial enzymes and agricultural chemicals.

Crystals themselves have been used in industry. For example, in a lot of soft drinks, the fructose is produced by crystalline glucose isomerase. Biological macromolecules provide the machines of life; crystallization is a mechanism of keeping them in a defined location. Looking to the future, one may see crystalline factories, but we still have a lot to learn about crystals and growing them before that occurs.


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