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Engineering's Denis Wirtz
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Denis Wirtz,
an associate professor of
chemical engineering, has developed a way to manipulate individual molecules of DNA with
powerful magnetic tweezers, dragging the double helices in three
dimensions with the help of a computer joystick. Wirtz predicts
that doctors could one day use the technique to guide minuscule
vesicles of medicine directly to a disease site, like a tumor,
without harming surrounding tissues--without, in fact, needing to
touch a patient at all.
Wirtz, who recently received $500,000 in grants from the National
Science Foundation and the private Whittaker Foundation, also
envisions his device influencing the imperfect field of gene
therapy. If single molecules of DNA can be manipulated, perhaps
fragments or even single genes could be introduced into existing
genetic material as a means of repairing mutations. (Wirtz has
already begun micromanipulation of genes, in fact, although that
work is in its infancy. ) His findings also have implications for
materials scientists, who might use the device to test the
strength of existing molecules and to design new ones.
A native of Belgium, Wirtz designed his magnetic tweezers in an
effort to learn the friction co-efficient of DNA-- a measure of
the polymer's elasticity and mobility--while on a fellowship in
Paris three years ago. He has been working on the tweezers since
joining the Hopkins faculty in 1995. Although other scientists
have used similar devices to tug on anchored DNA molecules, Wirtz
is the first researcher to move an untethered molecule.
Of course, DNA--or any other polymer--isn't magnetic. It must be
attached to something that is. So Wirtz jury-rigged a system of
proteins to tiny, spherical grains of iron oxide, some as small
as 15 billionths of a meter--thousands of times thinner than the
width of a human hair. First, he bathed the metal bits in a
solution of streptovidin, a chain molecule many times larger than
the crystals. Streptovidin forms a basket-like lattice around
each grain, which Wirtz filtered out by size. He then painted the
streptovidin with a common protein called biotin that acts like
glue around other molecules. Biotin, in turn, is quick to hook up
with DNA, which has staggered ends called telomeres that offer
the protein a pair of easy-to-find, strong grips. Biotin affixed
to streptovidin is the functional equivalent of a magnetic
molecular trailer hitch, strong enough to tow DNA while staying
stuck to the bead. Wirtz discovered that as he pulled on the
molecule with varying degrees of force, it underwent predictable,
and quantifiable, deformations. Under no stress, the sample
looked like the circular scribblings of a child. As he applied
the tweezers, the molecule became first trumpet shaped, then
nearly flat like twin strands of spaghetti.
For his experiment Wirtz chose a type of viral DNA known as
lambda-phage, because the 17- micron-long polymer can be seen
through the eyepiece of a standard microscope. But in theory, he
says, he could have chosen any edition of the molecule.
Wirtz hopes his magnetic tweezers will leapfrog a similar
micromanipulation tool, so-called "optical tweezers." Using laser
beams to create a force field, optical tweezers can also suspend
and shuttle small objects, including individual cells and genetic
material, without harming them or nearby tissue.
But Wirtz says his device is more powerful and less invasive, and
far less expensive to make (just $10,000 compared to $50,000).
--AM
Recognition for RNA--at
last
When professor of chemistry David Draper came to Hopkins 16 years
ago, he decided to tackle the relatively uncharted territory of
RNA research. The choice seemed an unlikely one at the time. DNA
(deoxyribonucleic acid) was all the rage among nucleic acid
chemists, while RNA (ribonucleic acid) was a much more fickle
material to work with.
Further, many scientists believed that the heart of gene
expression--the turning on and off of genes--resided at the level
of proteins binding to DNA. Proteins that associate with RNA were
relegated minor roles. Nevertheless, says Draper, "I guessed
RNA-protein interactions would be the next frontier."
He was right. Over the years, Draper and other scientists
improved techniques for synthesizing RNA. They learned, says
Draper, "RNA/protein interactions were important players in gene
regulation, and could be targets for drug development." Now, in
an article in the January issue of the British journal Nature
Structural Biology, Draper concludes that RNA-binding
proteins may have been the evolutionary precursors of DNA-binding
proteins.
Something like a condensed transcript of DNA, RNA is required for
the production of all proteins. Draper found that a protein
called L11, which binds to RNA and speeds the rate of protein
production, is remarkably similar to a class of proteins called
homeodomain proteins that bind to DNA. He also reported that the
two types of proteins use similar strategies to latch onto their
respective nucleic acids.
Draper's findings culminate 16 years of research at Hopkins,
during which he has received funding from the National Institutes
of Health. Last year, he received a prestigious MERIT award from
the NIH. The 10-year awards are one of the most coveted in
science.
L11, which resides in the bacterium Escherichia coli, has
existed for at least 2 billion years, and homeodomain proteins
for about 400 million years. Given that fact, and the
similarities between the two types of proteins, says Draper, it
is possible that the RNA-binding proteins came first, and that
when DNA emerged, it adopted, with slight modifications,
RNA-binding proteins.
The finding might not mean much unless you know that DNA and RNA
are very different. DNA, the famous double helix, folds into a
regular, orderly pattern. RNA is a single strand, a more
irregular scramble whose three-dimensional structure appears to
follow more complicated rules.
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