Accurate prediction of gene feedback circuit behavior from component properties

Rosenfeld, Nitzan; Young, Jonathan W.; Alon, Uri; Swain, Peter S.; Elowitz, Michael B.

doi:10.1038/msb4100185

Published November 13, 2007 | Version Published + Supplemental Material

Journal Article Open

Accurate prediction of gene feedback circuit behavior from component properties

1. Weizmann Institute of Science
2. Rosetta Genomics (Israel)
3. California Institute of Technology
4. McGill University

A basic assumption underlying synthetic biology is that analysis of genetic circuit elements, such as regulatory proteins and promoters, can be used to understand and predict the behavior of circuits containing those elements. To test this assumption, we used time‐lapse fluorescence microscopy to quantitatively analyze two autoregulatory negative feedback circuits. By measuring the gene regulation functions of the corresponding repressor–promoter interactions, we accurately predicted the expression level of the autoregulatory feedback loops, in molecular units. This demonstration that quantitative characterization of regulatory elements can predict the behavior of genetic circuits supports a fundamental requirement of synthetic biology.

Additional Information

© 2007 EMBO and Nature Publishing Group. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without specific permission. Received 11.6.07; accepted 12.9.07. This work was supported by grants from HFSP (to MBE and UA), NIH (R01 GM079771 and GM068763 to the Center for Modular Biology) and NSF. PSS was supported by the National Science and Engineering Research Council and by a Tier II Canada Research Chair.