This international research effort organized by senior authors Kevin Plaxco, professor in UCSB's Department of Chemistry and Biochemistry, and Francesco Ricci, professor at the University of Rome, Tor Vergata started when Ricci realized that all of the information necessary to detect transcription factor activities is already encrypted in the human genome, and could be used to build sensors. "Upon activation, these thousands of different transcription factors bind to their own specific target DNA sequence," said Ricci. "We use these sequences as a starting point to build our new nanosensors."
The key breakthrough underlying this new technology came from studies of the natural biosensors inside cells. "All creatures, from bacteria to humans, monitor their environments using 'biomolecular switches' shape-changing molecules made from RNA or proteins," said Plaxco. "For example, in our sinuses, there are millions of receptor proteins that detect different odor molecules by switching from an 'off state' to an 'on state.' The beauty of these switches is that they are small enough to operate inside a cell, and specific enough to work in the very complex environments found there."
Inspired by the efficiency of these natural nanosensors, the research group teamed with Norbert Reich, also a professor in UCSB's Department of Chemistry and Biochemistry, to build synthetic switching nanosensors using DNA, rather than proteins or RNA.
Specifically, the team re-engineered three naturally occurring DNA sequences, each recognizing a different transcription factor, into molecular switches that become fluorescent when they bind to their intended targets. Using these nanometer-scale sensors, the researchers could determine transcription factor activity directly in cellular extracts by simply measuring their fluorescen
|Contact: Gail Gallessich|
University of California - Santa Barbara