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.
Resources:
Recent
interviews:
Brian
F. Beaton
Technology
Commercialization Project Manager
Langley
Research Center
Dr.
Paul Schenker
Director, Planetary Robotics Laboratory
Jet Propulsion Laboratory
Dr.
Christopher Dellacorte
Oil-Free Turbo Machinery Technical Leader
Glenn Research Center
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