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A digital test for toxic genes
Date:1/29/2014

are hindered by the toxicity of the genes that they wish to overexpress.

Prof. Ruppin's laboratory builds large-scale software models of cellular metabolism, one of the most fundamental aspects of life. These models convert physical, chemical, and biological information into a set of mathematical equations, allowing scientists to learn how cells work and explore what happens if they are tweaked in certain ways. The newly developed algorithm, Expression Dependent Gene Effects, or EDGE, predicts what happens if scientists manipulate cells to overexpress certain genes. EDGE allows biotechnologists to foresee cases in which the overexpressed genes become toxic and then direct their efforts toward other genes.

To validate their method, TAU researchers used genetic manipulation tools to overexpress 26 different genes in E. coli bacterial cells. Comparing the results of their computer simulations with the actual growth of the overexpressed strains that was measured in the lab, they saw that EDGE was able to predict which of the overexpressed genes turned out to be lethal to E. coli. EDGE was also successful in identifying cases of foreign genes that were toxic to E. coli, as the researchers learned from comparing the simulations' results with data collected by their collaborators at the Weizmann Institute of Science.

Beyond bacteria

EDGE's applications appear to extend beyond bacteria. The researchers conducted tests showing that the genes EDGE predicted to be toxic when overexpressed are expressed at low levels not only in microorganisms like bacteria, but also in multicellular organisms, including humans. The researchers say these results reflect the vital evolutionary need to keep the expression of potentially deleterious genes in check.

"Although EDGE's current focus is biotechnology, gene overexpression also plays a central part in many human diseases, particularly in cancer. We
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Contact: George Hunka
ghunka@aftau.org
212-742-9070
American Friends of Tel Aviv University
Source:Eurekalert

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