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Chemical Engineer Kao Explores Antibiotic Synthesis With DNA Chips

ycin for five days. The nonmutant produces it for only one. If the specific mutation can be located, Kao reasons, perhaps it can be introduced into other antibiotic-producing bacteria to increase their yields.

DNA microarrays

Without a tool known as the DNA microarray, or DNA chip, Kao's finding may not have been possible. First developed a decade ago at Stanford in the lab of biochemistry Professor Patrick Brown, microarrays use both computer technology and DNA base pairing to track the expression of thousands of genes simultaneously. The technique has tremendous potential for the study of biological processes where numerous genes work in concert--an apt description of antibiotic synthesis.

A microarray consists of single-stranded DNA arranged on a wafer the size of a postage stamp. The genetic sequence of the DNA tethered to the chip is known. Then researchers add a sample with an unknown composition of fluorescently labeled DNA molecules. The base pairs in the sample's single-stranded DNA, groups of which correspond to individual genes, stick to similar, or homologous, regions of the DNA tethered to the chip. The presence of the resulting double-stranded DNA reveals the base-pair sequence and the amount of that sequence in the added sample.

One way to measure gene expression is to measure levels of messenger RNA--that's RNA that translates the genetic information of DNA into proteins. Accordingly, one can go backwards and make DNA copies of all RNA transcripts in the mutant bacterial cultures of interest. With this clever trick, one can get DNA that can bind to the DNA already on the microarray, and the concentrations accurately reflect gene expression.

In Kao's experiment, DNA copies of RNA from cultures of erythromycin-producing bacteria were infused with fluorescent dye and applied to the microarray.

"This experiment revealed that the RNA transcript abundance of the erythromycin-producing genes remained higher fo
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Source:Stanford University


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