RA cross-disciplinary research team from the University of Maryland has shown for the first time that enzymes will perform their normal biochemical functions when electronically placed within a man-made “biochip” — a feat the school calls a major advance in the development of biochip technology for in vitro drug discovery and delivery. The researchers created the biochip as a tiny bioprocessing “factory” containing multiple processing sites that are addressed fluidically, electrically, and optically. They then used electrical voltage to place the naturally occurring biopolymer chitosan, which serves as a platform for assembling biomolecules. In the breakthrough reported last week, they successfully assembled an enzyme from bacteria within the biochip, and showed that it can catalytically convert a small molecule (SAH) to adenine and SRH products — both of which are essential for cell-cell communication. “We have now demonstrated perhaps the key advance needed to realize what we seek, a powerful laboratory tool for drug discovery,” said Gary Rubloff, UM professor and director of the Maryland NanoCenter. “We hope to enable scientists and physicians to create better, more effective drugs more rapidly and at reduced cost.” One targeted application is to develop drugs that can interrupt “quorum-sensing.” In quorum-sensing, a bacterium generates a small molecule called an autoinducer. The autoinducer is a signal to other bacteria, which, if present, create a quorum that is pathogenic, leading to an infection. In testing, when the biochip-created enzyme converted SAH to adenine and SRH, the enzyme performed the first two primary reaction steps in the production of autoinducer-2 (AI-2) by E coli bacteria. By reproducing that type of reaction, the microfactory can support drug discovery, its developers say. Candidate drugs can be applied in the biochip to test their ability to suppress or interrupt the production of the autoinducer as well as to identify which part of the biochemical synthesis pathway is affected by the drug. Drugs that suppress the autoinducer synthesis will not only serve as good candidates for new antibiotics, but they promise a new strategy for antibiotic therapy. Conventional antibiotics work by killing bacteria, but in doing so they stimulate mutations that provide resistance to the drugs — a problem the researchers’ approach could overcome by interfering with the communication between bacteria rather than killing them. The team also envisions using programmable biological microfactories as tools for rapid screening of new drugs to help determine efficacy prior to time-consuming, expensive clinical trials. Go to: University of Maryland

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