Impedance Matching

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Science  02 Dec 2005:
Vol. 310, Issue 5753, pp. 1393
DOI: 10.1126/science.310.5753.1393b

The current vogue for treating metabolic and regulatory pathways as circuits in which parts can be swapped in and out, with sensors at the input side and cellular behavior at the output side, has been driven by the ability to construct sensors by modifying natural ligand-binding receptors and to insert heterologous genetically coded components. Invasin is a cell-surface protein of Yersinia pseudotuberculosis that initiates bacterial uptake by binding to integrin, a protein on the surface of some mammalian cells, and previous work has shown that transferring the inv gene into Escherichia coli is sufficient to enable it to invade integrin-expressing cells. Anderson et al. have engineered E. coli in which inv is under the control of the promoter from fdhF, a gene whose expression is induced by hypoxia (one characteristic of tumor microenvironments). They discovered that in order to dial down the basal level of inv expression in their construct, it was necessary to etiolate the wild-type ribosome-binding site by randomizing flanking bases in a library of 106 members and screening for the handful of clones in which sensor input and behavioral output were matched so as to support a strictly anaerobic-dependent invasion. — GJC

J. Mol. Biol. 10.1016/j.jmb.2005.10.076 (2005).

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