July 14, 2008 -- Beyond diagnosing broken bones, X-rays could soon help doctors develop antiviral drugs.
By focusing powerful X-rays onto a herpes virus, scientists from the University of California, Los Angeles, have created the first image of a virus without the aid of stains or dyes.
The technique, known as X-ray diffraction microscopy, could lead to new drugs for a variety of diseases.
A similar version of the technology, known as X-ray crystallography, has been used for years to determine the structure of many important proteins, including the double helix of DNA.
"This is an enormously important technique," said John Miao of UCLA, the lead researcher on the project. "Lots of Nobel Prizes have been awarded because of this."
The problem with X-ray crystallography is that it only works on crystals, which have precise arrangements of identical (or nearly identical) units. DNA and some proteins are repetitive enough to be made into crystals.
Other proteins, particularly those found on a cell's membrane, can't be crystallized because they are too flexible and variable. Whole cells can't be crystallized either.
"Cells are just like humans, and no two humans are exactly alike," said Miao.
Miao and his colleagues worked around this limitation by using what are currently the most powerful X-rays on Earth, located at the SPring-8 synchrotron in Japan.
The researchers selected a herpes virus because of its relatively large size (100 to 200 nanometers) and its medical significance. They put the virus into the synchrotron and then aimed X-rays at the sample. A camera on the other side detected the slight variations in light exiting the other side, and a computer algorithm pieced the image back together.
In doing so, Miao and his team created the first picture of a single, unstained virus, which was also three orders of magnitude smaller than images obtained with other techniques.
Other pictures of cells and viruses can be obtained by drying them and slicing very thin sections, then piecing them back together, but the process can destroy important information.
Right now the pictures are still fairly grainy at a resolution of 22 nanometers, but the scientists say more powerful X-rays, being developed at Stanford University and in Germany, will create more detailed images of the structure of even smaller proteins and cells.
Those images would be a boon for drug researchers, said Miao.
"From the structure of a protein one can understand the protein's function," he said. "Then we can develop drugs to deactivate that protein."
Thomas Earnest from the Lawrence Berkeley Laboratory thinks that while Miao's method will never reach the atomic resolution that X-ray crystallography achieves, it is nevertheless an important development.
"This approach for looking at biological specimens or protein complexes is very valuable," he said. "I'm really excited about this work. John is doing a great service to the entire biological community."
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