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UF researchers develop tiny tool kit to study genes and unhealthy cell

University of Florida

A decade-old international effort to map the human genetic code is expected to wrap up this summer, giving scientists all the information they need to identify the genes behind diseases ranging from diabetes to heart disease.

Before researchers can turn the wealth of data provided by the Human Genome Project into new medical treatments, they'll need tiny tools to rearrange genes or gene parts and monitor the impacts. Now, University of Florida researchers are reporting success in developing a molecule that may serve as one such tool. Researchers have also created other tools that may identify disease or toxins in single cells before they invade the body.

On Thursday, in an achievement widely heralded as a first, researchers in France announced they had used gene therapy to cure a rare immune disorder. The UF research, which created a synthetic DNA molecule, has the potential to play a role in such achievements by allowing researchers to monitor the impacts of genetic therapy.

"This could be a way to ensure that you're producing the proper amounts of a substance or chemical, or the amounts that you expected for whatever time period you wanted," said Sheldon Schuster, professor and program director of the University of Florida's Biotechnology Program and one of the researchers.

Weihong Tan, an assistant professor of chemistry at UF and the UF Brain Institute, recently collaborated with Schuster and two other UF researchers to construct what the researchers describe as a "synthetic DNA beacon."

Published earlier this year in Angewandte Chemie International Edition, a prominent international chemistry journal, the research by Tan, Schuster and UF researchers Jeffery Li and Xiaohong Fang produced a molecule that contains a "photophore," a substance that lights up only in the presence of a target protein, DNA or RNA molecule. Researchers can use laboratory equipment to monitor when the light appears, allowing them to determine the absence or presence of the target protein or gene. The potential application is for such molecules to be used to detect the presence of, say, disease- or cure-related proteins or genes in extremely low concentrations.

"What this DNA biosensor and other biosensors do is detect very small quantities of biological molecules with a high degree of specificity," Schuster said.

Tan also has crafted probes, thousands of times thinner than the human hair, that physicians may one day insert into individual cells to test for disease. Additionally, he's pioneering microscopic "nanoparticles" that could carry drugs directly to sickly cells to treat or exterminate them. All the tools meld biotechnology with the fast emerging field of nanotechnology, which endeavors to create self-assembling molecular machines.

"In order to study cells and what goes on inside of them, you have to have tools or materials much smaller than the cells," Tan said. "In our lab, we develop and test these tools, which are important to today's biomedical research and tomorrow's medical treatment."

Tan's ultrasmall probe is similar to the DNA beacon, but its florescent dye-containing tip indicates biochemicals or substances in cells rather than genes. Measuring just 30 nanometers -- a nanometer is one billionth of a meter -- it does not harm or kill the cell, and so can be used to monitor chemical changes in living cells. In tests, the probe has successfully identified glutomate, which is released when strokes occur. Researchers hope such probes could be used to determine trace concentrations of glutomate released at the start of a stroke, allowing physicians to treat the patient in time to prevent major damage.

Another major potential application of Tan's research is earlier detection of antibodies.

"You'll be able to detect antibodies much more efficiently and much easier, because you can detect them at much lower concentrations," he said.

The sensors also could be used as early indicators of chemical contamination pollution or chemical warfare, Schuster said. "The military certainly has a need to know if either military or civilian populations are being bombarded with small concentrations of toxins," Schuster said. "...The earlier you can detect them, the quicker you can respond."

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Color or black & white photo available with this story. For information, please call News & Public Affairs photography at 352-392-9092.

Sources: Weihong Tan, 352-846-2410, tan@chem.ufl.edu
Sheldon Schuster, 392-8408, schuster@biotech.ufl.edu

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