Madison, Wisconsin
April 16, 2009
Using the same protein molecule
that scientists have used for decades to copy genetic material,
researchers have developed a molecular motor for propelling DNA.
The work, reported in the online edition of the
Journal of the
American Chemical Society, shows that RNA polymerase, an
enzyme that scientists routinely use to copy DNA, can act as a
propulsion system able to both move and direct molecules of DNA
in specified ways.
The work demonstrates the ability to precisely control the
motion of billions of DNA molecules at once and, through
external stimuli, confer autonomous decision-making that sets
the stage for massive, but greatly miniaturized experimental
systems.
"This lays the basis for experiments that configure themselves
and operate themselves," says David C. Schwartz, a
University of Wisconsin-Madison
genomicist and the senior author of the new study. "It will be
possible to design intelligent systems to do billions of
experiments" at once.
The new technology described by Schwartz and his colleagues
could conceivably replace the armies of robots engaged in
mundane and arduous lab work, but that are now essential for big
science projects such as genome sequencing and analysis.
"Up until now, we've done this kind of work with robots,"
Schwartz explains. "Biotechnology robots dumbly move samples
around. Here, we have intelligent agents that are single
molecules - they can make decisions and they can evolve. We have
something very new and powerful and miniature."
Such technology, Schwartz argues, can help address the pressing
need in modern biology for new experimental systems capable of
acquiring large, complex data sets. DNA molecules, hitched to
their polymerase motors, he says, can be the basis for massive
parallel assays where the souped-up molecules are regulated by
different experimental factors and can reorganize themselves to
become tiny, discrete experiments.
Billions of experiments could be conducted in a single test
tube, Schwartz says. Such miniaturized and "intelligent"
capacities address one of the key barriers to conducting the
experiments required to answer some of biology's most pressing
questions. For example, the technology could be put to work to
comprehensively test millions of potentially therapeutic
compounds to speed the development of new drugs, a process that
now takes many years. It could also aid the development of DNA
computing.
The motorized molecules steer themselves by sensing "fuel," a
chemical nutrient that draws the molecule in, by temperature, or
through nanoscale geometric patterns on the surface of a culture
plate. "The molecules can make decisions based on the
environment they find themselves in," Schwartz notes. "You can
set them loose, but they sense and interact with their
environment. And what makes it hugely scaleable is it is very
simple."
Schwartz explains that scientists have for years been toying
with such molecular complexes and have developed a bag of
miniature tricks, the ability to attach cargo, for example, to
make the molecules act like little burros.
But what no one bothered to explore, he says, was the apparent
motion of the DNA molecule in free space as it was copied by the
RNA polymerase. Schwartz and his colleagues, including fellow
UW-Madison researchers Hua Yu, Kyubong Jo, Kristy L. Kounovsky
and Juan de Pablo, found that the stiff rods of DNA created when
a molecule is copied by RNA scoot like motorboats: "The RNA
proteins act like little motors. The complex can then propel
itself through space."
Once set in motion, the molecules can be sped along and directed
by placing chemical nutrients in specified gradients. The DNA
can sense the nutrient and is drawn toward the source as a form
of fuel.
The new Wisconsin study was supported by grants from the
National Institutes of Health and the National Science
Foundation through the Nanoscale Science and Engineering Center. |
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