March/April 2002
FSU technology gives scientists
the first good look at TB cells
By Mark Riordan
For decades, scientists have wanted to combat diseases with drugs "smart" enough to shut down the proteins that control cell activity on the surface of diseased cells. Their hypotheses, however, remained largely untested because the technology did not exist. Now it does, and it's at Florida State University.
"We've wanted to look at the surface proteins for decades," FSU biophysicist Timothy Cross said. "But the stumbling block has always been technological in nature: They're hard to handle, observe, purify, manipulate, in short, to experiment with."
Using an $8.1 million grant for five years from the National Institutes of Health, Cross will bring together the world's most sophisticated scientific instruments to unlock the secrets of these activity-controlling proteins. Using x-ray crystallography, electron microscopy, magnetic resonance spectroscopy and high-resolution mass spectroscopy, the scientists will inspect cells at their most fundamental and elemental levels.
Cross and his team are bringing the technology
to bear on one of the world's most persistent and prevalent killers:
tuberculosis. They will reduce a bacterium to its constituent
parts and then identify and classify the proteins that make cell
communication (and in TB's case, that means infection) possible.
Cross chose TB, he said, because it's the worlds' No. 1 disease
killer, infecting nearly a third of Earth's population and growing
more drug resistant. Cross said the disease generally remains
dormant until the body's immune system becomes compromised.
"That's why we see such a high death rate in central and southern Africa," he said. "The people there are not dying from AIDS, as many believe, but from TB after AIDS has reduced their immunity to infection."
Cross, an internationally respected researcher at the National High Magnetic Field Laboratory, said the resources at FSU make the research possible.
"There's been a convergence of technology
here at the university that made NIH fund this research,"
he said.
The membrane proteins that the team is targeting are the most
difficult, biologically speaking, to work with. They exist in
a gooey environment that protects the cell's interior as a coat
of wax protects the paint on a car.
Since the technology has not existed to break down this environment for closer study, scientists have concentrated on the water-soluble cell interior.
It has been difficult, Cross said, to get drugs to pierce the protective waxy coating and remain in the watery world of a cell's interior long enough to kill it. But that's the best scientists could do, given the technology.
Joining him in his efforts are FSU's Michael Chapman, Alan Marshall and Kenneth Taylor, along with nine other researchers from six universities and the Lawrence Berkeley National Laboratory.
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