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Synthetic gene circuit allows precise dosing of gene expression
Date:3/10/2009

HOUSTON - Researchers have crafted a gene circuit that permits precise tuning of a gene's expression in a cell, an advance that should allow for more accurate analysis of the gene's role in normal and abnormal cellular function.

This gene "dosing effect" is achieved by installing a negative feedback loop in the synthetic gene circuit, a concept similar to signal distortion control in electronics, a team led by scientists at The University of Texas M. D. Anderson Cancer Center reports this week in the Online Early Edition of the Proceedings of the National Academy of Sciences.

"To understand what a gene does, you need to change its expression and observe the results. Present methods do not allow close control of gene expression," said senior author Gbor Balzsi, Ph.D., assistant professor in M. D. Anderson's Department of Systems Biology.

Knocking out genes is an all-or-nothing approach, and suppressing them with small interfering RNA has undesired effects. Transfecting cells with a gene expression vector overexpresses the gene, but still in an uncontrolled way, Balzsi noted. The synthetic gene expression system the researchers developed in a yeast model would allow more detailed investigation of a gene's effects.

"Say you have a gene that is involved in resistance to drugs, and you want to know how much protection the cell gets at different levels of expression," Balzsi said. "You place the gene circuit in the cells set at first to fully repress the protective gene. You then tune gene expression to the desired level and add chemotherapy to the cell culture, to discover the relationship between the gene and cellular defense against the drug."

The gene expression circuit built by Balzsi and colleagues produces a linear relationship between the dose of an inducer that regulates the circuit and the level of gene expression.

Gene network built to repress

The team first synthesized a gen
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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