High-powered living DNA cannon

We all know that a viral infection can be developed extremely quickly, but in fact

it's even more dramatic than that - the process is literally explosive.

The pressure inside a virus is 40 atmospheres, and it is just waiting for an

opportunity to blow up. The virus is like a living DNA cannon. How this cannon

functions has been mapped by Dr. Alex Evilevitch at the Department of

Biochemistry at Lund University in Sweden. This is knowledge that will have

applications in gene therapy, drug development, nanotechnology and the

treatment of infections. This involves a new type of virus research that is based

more on physics than biochemistry. Perhaps it could be called virus biophysics.

Alex Evilevitch took his doctorate at Lund in physical chemistry and worked for a

few years at UCLA.

"There I met Professor William Gelbart, who predicted on theoretical grounds

that the pressure in a bacteriophage - a virus that attacks bacteria - must be 40

atmospheres," explains Alex Evilevitch. "This roughly corresponds to the

pressure at a depth of 400 meters under the sea. That's twenty times more than

the pressure in a car tire and ten times more than the pressure in an unopened

bottle of champagne. Using measurements, I was able to confirm that Professor

Gelbart's prediction was accurate."

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Evelevitch's research has attracted considerable attention and landed him a prize

for the best research of the year in 2003 at UCLA and a 2004 Chancellor's

Award at the same university. The list of recipients of the first prize includes

several scientists who went on to win a Nobel Prize. But even though "virus

biophysics" is a hot research field in the U.S., Evilevitch chose to return to

Europe, where only a few research groups pursue such research.

"It turns out that Lund University has unique equipment for this research," says

Alex Evilevitch. "At the National Center for High-Resolution Electron Microscopy

there is a helium-cooled electron microscope. The cooling makes it possible to

examine sensitive biological material. There are only a few electron microscopes like this in the entire world, and I had the privilege to work with it during the first

months it was in regular use in research. Right now I'm busy putting together a

research team in virus biophysics."

The virus that infects cells in plants, animals, and humans penetrates in its

entirety into the cell and works inside. But bacteriophages are viruses that attack

bacteria, working from the outside. The bacteriophage looks lik 20-faceted

soccer ball with a tail, or, perhaps rather a syringe needle. It's only about 60

nanometers in size (one nanometer = a billionth of a millimeter).

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But its DNA, its genetic material, is a strand that is about 17,000 nanometers long! To get it into such a small body, everything has to be packed tightly. What's more, the DNA has a negative electrical charge, which makes the tangled up strands repel each other.

When the bacteriophage comes into contact with a certain type of receptor on the surface of the bacteria cell, a canal in the tail opens and its DNA violently

rushes into the cell. Once inside this DNA is reduplicated a million or more

times. At the same time new protein shells are constructed for new virus

particles. There is a special molecular motor that acts like a screw in its threads,

rotating and pressing the DNA into the shell one bit at a time, under rising

pressure. It's the most powerful molecular motor known.

Alex Evilevitch has continued to publish his research findings after his return to

Lund. The latest (in Biophysical Journal, January 2005) contains measurements

of the length of the DNA strands that are propelled into the bacteria. An

important finding in that study is that it is a purely mechanical force, not a

chemical or biological process that is at work when the virus DNA explodes.

At the moment Evilevitch is developing methods to influence the mechanical

packing force in order to make it possible to squeeze more DNA into the virus

capsule.

"One method used today for cloning a gene sequence is to insert it into

bacteriophage DNA," says Alex Evilevitch. "After the molecular motor has worked

this DNA into the virus capsule, the virus is then allowed to infect a bacteria

culture. This in turn will produce millions of copies of the alien DNA. This

technique is limited by the fact that there is only room for short sequences in the

capsule. If it proves to be possible to influence the force needed to pack DNA,

then that will enable even longer DNA strands to be pressed in. That would be a

significant technological advance that would benefit future gene therapy, cloning

and the general development of molecular biology."

Other ideas circulating in this new scientific field involve the use of

bacteriophages as living syringe needles to inject drugs into cells. The protein

casing of bacteriophages, which is strong enough to withstand the inner

pressure, is also of interest to scientists. In nanotechnology the search is on for

suitable packaging for carbon tubes and other nanometer-size structures.

Perhaps protein shells will provide the key to how sturdy containers can be

constructed. It is also plausible to use bacteriophages in treating infected

wounds, and in the U.S. trials are underway to create safer foodstuffs by

controlling bacterial processes with bacteriophages.

Notes

Alex Evilevitch can be reached via e-mail at Alex [dot] Evilevitch [at] biokem [dot] lu [dot] se

This story has been adapted from a news release -

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