The development could provide a foundation for a new family of biologically-based mechanisms able to detect common drugs, chemical weapons and other small molecules. By allowing manipulation of this cellular protein machinery known as nuclear receptors the technique could also lead to new methods for producing enzymes and important pharmaceutical compounds.

"We are hijacking these nuclear receptors for a new set of purposes," explained Donald Doyle, assistant professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology. "We want to change the nuclear receptors themselves so they don't recognize what they normally recognize, and instead recognize the small molecules we want to detect. That would allow us to develop a new type of sensing mechanism."

A paper published in the September 27 October 1, 2004 issue of the journal Proceedings of the National Academy of Sciences describes how Doyle's research team which also included Lauren Schwimmer, Priyanka Rohatgi, Bahareh Azizi and Katherine Seley modified one type of nuclear receptor to bind a drug compound to which it previously did not respond. Based on this success, the researchers hope to demonstrate broader application with other small molecules.

The work was sponsored by the Research Corporation, the Seaver Foundation and the National Science Foundation.

Nuclear receptors are ligand-activated transcription factors contained in cells. When activated by specific small molecules, the nuclear receptors initiate a complex process that results in gene expression. Because these receptors play a vital role in controlling cellular response to these small molecules, scientists have been attempting to understand them and solve their molecular structures with a
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Contact: John Toon
john.toon@edi.gatech.edu
404-894-6986
Georgia Institute of Technology Research News
3-Oct-2004