Research method tracks chemicals

What bacteria can do effortlessly, scientists have only just begun to grasp. Biochemists at the Medical Center have developed a technique to engineer bacterial proteins to act as bioelectronic sensors for a multitude of chemicals.

"The goal is to try and use proteins to detect interesting chemicals in the body or environment," said lead researcher and Associate Professor of Biochemistry Homme Hellinga. The findings of Hellinga's study were reported in the Aug. 31 issue of Science.

When attached to electrodes, these proteins produce an electric signal indicating the identity and concentration of specific chemicals. The technology has already been used to detect glucose in blood serum and maltose in beer, demonstrating its ability to pick out specific substances in a complex mixture.

"It essentially borrows out of nature's book," said Hellinga. The engineered proteins are based on bacterial periplasmic binding proteins that bacteria use to detect food sources and avoid toxic chemicals. Because of the variety of bacterial life, the proteins form a basis for a great number of chemical sensors.

Hellinga envisions broad applications in medicine. Biosensors could instantly detect chemicals in patients, eliminating the expense and time that current lab methods waste.

For example, Hellinga said, the technology could be used to monitor glucose levels in diabetic patients, perhaps providing a continuous basis for an artificial pancreas. Physicians could accurately monitor blood levels of anesthetics used during surgery or kemotherapeutics in cancer patients, rather than relying on vital signs to imprecisely dictate proper doses. "Metabolic markers" could be used to more accurately detect specific diseases, and drug tests could be dramatically improved.

"These sensors give a molecular picture of a patient," Hellinga said.

In one experiment, the researchers coated a gold electrode with bacterial maltose binding proteins that were tethered to metal ruthenium groups. When maltose was added, the sugar contorted the proteins' shapes, producing a voltage difference across the metal and an electric current proportional to the maltose concentration.

Hellinga noted that when the scientists re-engineered the protein, it dramatically changed and began detecting zinc rather than maltose, demonstrating the versatility of the technique.

"The next step is to do it with environmental chemistry... to try and redesign proteins to bind new things," Hellinga said. Biosensors could provide a simple method for detecting chemical gases, pollutants and toxins in air and water.

Hellinga sees biosensor technology eventually taking part in nanosystems that could patrol the blood and, like bacteria, affect their environment based on the chemicals they detect. "But that's a 10-year project... well, at least 10 years," he said.

Hellinga is joined in his research by David Benson of Wayne State University, Scott Trammell of the Naval Research Laboratory in Washington, D.C. and Duke researchers David Conrad and Robert de Lorimier.

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