Johns Hopkins Magazine -- April 1997
Johns Hopkins Magazine

APRIL 1997

S C I E N C E    &    T E C H N O L O G Y

Comet "minutemen"... dragging double helixes in 3-D... RNA's adaptive ability... obscured by a doughnut of dust

On Hale-Bopp's trail
Billed as the comet of the century, Comet Hale-Bopp is in its zenith of visibility until mid-April. Rush out and see it just before dawn or shortly after sunset, in the Northern Hemisphere-- it won't orbit the Earth again for another 3,000 years.

Hopkins comet afficionado Hal Weaver began studying the comet soon after astronomer Alan Hale and amateur astronomer Thomas Bopp discovered the comet in July 1995. "We're like minutemen," says Weaver. "When a comet comes along, we drop everything."

With physics and astronomy professor Paul Feldman, another veteran comet astronomer, Weaver has already yielded a spate of discoveries. Including:

Comet Hale-Bopp offers clues to the composition of the early solar system.
Based on observations made with the International Ultraviolet Explorer satellite, Feldman concluded that Hale-Bopp's gas and dust production rate is among the most prolific of any comet's, an indication that the comet's nucleus is huge. Using the Hubble Space Telescope, a team led by Weaver pinpointed the nucleus' diameter at 30 to 40 kilometers (about 19 to 25 miles). "I think it's in the category of monster comet," says Weaver.

To the scientists' puzzlement, Hale-Bopp is not abiding by an astronomical rule called the "brightening law," which holds that comets should brighten sharply the closer they speed toward the sun. As Hale-Bopp approaches the sun, Weaver observed, the comet is not brightening as much as it should. "We're puzzled at this point," he says. Astronomers have proposed several hypotheses, says Weaver, but none jive with the data collected so far. More may be learned when Hale-Bopp speeds away (after April 1).

Though Hale-Bopp will still be a spectacular astronomical event, notes Weaver, it will probably turn out to be slightly fainter than last spring's Comet Hyakutake.

Weaver also concluded that between April and September 1996, the amount of dust exiting the comet increased by a factor of two, while the amount of water vapor leaving increased by a factor of 14.

"The vaporization of water from the surface is what drags the dust off," explains Weaver. Theoretically, then, the ratio of vaporizing water to driven dust should remain roughly steady. Again, the astronomers are puzzled. One possibility is that the dust and water are coming from different regions of the comet, says Weaver.

As is the case with other comets, the juiciest scientific gleanings will pertain to Hale-Bopp's composition.

Comets are balls of dust, rocks, and ice--dirty snowballs, if you will. As a comet speeds past the sun, ice vaporizes from the nucleus, forming a cloud of gas called a coma. Gas and dust trailing behind the comet's nucleus is called the tail.

Astronomers believe that comets were formed during the early days of the solar system, and were flung into far distant orbits (Hale-Bopp is probably a visitor from the Oort cloud, 9 trillion miles from the sun), where they are relatively sheltered from the ravages of the universe and thus remain relatively virgin relics of the primordial solar system.

By studying the composition of Hale-Bopp and other comets, astronomers infer what the composition and conditions of the early solar system were like. "Gases in the coma of the comet are a clue about where the comet formed in the solar system," says Feldman.

Weaver, Feldman, and other astronomers stopped using the Hubble Space Telescope to view Hale-Bopp last October, when the comet's closest approach to the sun began. Gazing upon Hale-Bopp when the comet is angled close to the sun would seriously damage the telescope.

Now Weaver is examining the comet through an infrared telescope at Mauna Kea, Hawaii. "We want to take an inventory of the composition of the comet, of everything you can measure." Theory says the list should include complex molecules including acetylene, ethane, and complex hydrocarbons, and Weaver wants to confirm this.

Just as he did 11 years ago for Comet Halley, Feldman is sending up a sounding rocket carrying a telescope payload to look at Hale-Bopp. The rocket is scheduled for launch from White Sands, New Mexico on April 5, and will be steered by Hopkins graduate student Jason McPhate.

About 200 miles above the desert floor, the rocket will separate from the payload, a Hopkins-built spectrograph that observes ultraviolet light. The profile of ultraviolet wavelengths emanating from Hale-Bopp correspond to particular chemicals. One that Feldman's team is particularly interested in is carbon monoxide.

"Carbon monoxide is very volatile. It only condenses in very cold temperatures," says Feldman. By mapping the distribution of carbon monoxide in Hale-Bopp's coma, the team hopes to find out about the comet's temperature when it was formed. --MH

Manipulative magnetic tweezers
Star Trek devotees undoubtedly remember Dr. McCoy curing space-sick voyagers with a deliberate wave of his mysterious magic wand. The gimmick seemed almost absurd then, but the device might prove an inadvertent foreshadowing of a tool now being perfected at Johns Hopkins.

Engineering's Denis Wirtz
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.

The alpha helix (blue) of a protein fits snugly into a spacious groove on DNA (left). But in RNA, a deeper and narrower groove presents more of a challenge.
At regular intervals along its length, the DNA landscape indents. Each indentation, called a major groove, is the perfect size and shape for accommodating a cylindrical outcropping of protein called an alpha helix. One type of DNA-protein binding occurs when the alpha helix nestles into the major groove. RNA also has a major groove, says Draper. "But it is very deep and extremely narrow. There is no way to fit an alpha helix in there."

But when Draper and his co-workers examined the structure of L11 through a technique called nuclear magnetic resonance (NMR), and compared it to the known structure of several homeodomain proteins, they discovered that specific regions of L11 have "spectacular structural similarity" to regions of certain homeodomain proteins. By searching a genetic database, his team found homologues to L11 in all three phylogenetic domains. In other words, "every organism has something like an L11," says Draper.

Further, even though RNA's major groove appears to be too tight a squeeze for an alpha helix, the researchers conclude that L11 does indeed bind near the major groove of RNA. Apparently, RNA contorts itself to allow L11 to grab hold. "RNA seems to have more flexibility and more of a variety of structures than DNA, which allows it to adapt and accommodate proteins," says Draper.

The chemist is now examining other RNA binding proteins. He suspects that the strategy employed by L11 "will be a major theme" in how proteins bind RNA. --MH

A doughnut of dust
Imagine what you would see if you tucked a small but powerful flashlight into the hole of a doughnut, and turned off the lights. If you looked at the doughnut head on, you'd see an intense disk of light. But if you viewed the doughnut from its side, you would see a fan of light emanating from it, though not the light source itself. With a little imagination, that is what is pictured here: the sideview of a doughnut.

It is actually an image of the Seyfert 2 galaxy Markarian 463 taken with the Hubble Space Telescope's Faint Object Camera.

The small white lines in this image of a Seyfert galaxy indicate that light fans out from a nucleus at the + sign.
Seyfert galaxies are spiral galaxies that are believed to contain extremely powerful energy sources, called quasars, in their nuclei. Quasars are believed to be instrumental in forming galaxies, and to be driven by black holes.

Astronomers observed what they believed were two types of Seyfert galaxies: Seyfert 1 galaxies, which show an intense bright spot at their centers surrounded by dust, and have an optical spectrum identical to that of a quasar; and Seyfert 2 galaxies, which are slightly fainter than Seyfert 1 and have a different spectrum. Some astronomers proposed that perhaps only Seyfert 1 galaxies are powered by quasars.

But graduate student Christina Tremonti, research scientist Alan Uomoto, and their colleagues say their images of Markarian 463 support an alternative idea called the unified theory of active galactic nuclei. According to this theory, Seyfert galaxies 1 and 2 are actually the same type, simply seen from different perspectives.

An ultraviolet image of Markarian 463 shows a cone of light fanning out from an apex. In the fan's center is a bright spot, which was once believed to be Markarian 463's nucleus. But images taken in polarized light revealed otherwise.

When light travels away from Markarian 463, it scatters off dust and electrons in space, and is polarized in a single direction. Polarizing filters can thus reveal the direction light is traveling (indicated by the short white lines).

When the Hopkins team inspected the polarization data, they found that the bright spot believed to be Markarian 463's nucleus is actually "a decoy," Tremonti reported in January at a meeting of the American Astronomical Society, in Toronto. The polarization images reveal that the cone of light fans out from an apex (the plus sign) thousands of light-years away from the bright spot. This region, which looks anything but bright in the image, is the true nucleus, says Tremonti. Apparently, the nucleus is obscured by a doughnut of dust (which you have to imagine--it is not visible in the photograph.) Thus, Seyfert 2 galaxies may actually be a sideview of Seyfert 1s.

So what are the two bright spots in the image? "Good question!" says Tremonti. "It's a matter of speculation." Another puzzling fact remains. "If you have this doughnut model, you'd expect to see two cones of light," one emanating from both sides of the doughnut hole,' says Tremonti. "We see only one." --MH

Written by Melissa Hendricks and Adam Marcus (MA '96).