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Construction of an in vitro bistable circuit from synthetic transcriptional switches

Kim, Jongmin and White, Kristin S. and Winfree, Erik (2006) Construction of an in vitro bistable circuit from synthetic transcriptional switches. Molecular Systems Biology, 2 . Art. No. 68. ISSN 1744-4292. PMCID PMC1762086. doi:10.1038/msb4100099.

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Information processing using biochemical circuits is essential for survival and reproduction of natural organisms. As stripped-down analogs of genetic regulatory networks in cells, we engineered artificial transcriptional networks consisting of synthetic DNA switches, regulated by RNA signals acting as transcription repressors, and two enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H. The synthetic switch design is modular with programmable connectivity and allows dynamic control of RNA signals through enzyme-mediated production and degradation. The switches support sharp and adjustable thresholds using a competitive hybridization mechanism, allowing arbitrary analog or digital circuits to be created in principle. As an example, we constructed an in vitro bistable memory by wiring together two synthetic switches and performed a systematic quantitative characterization. Good agreement between experimental data and a simple mathematical model was obtained for switch input/output functions, phase plane trajectories, and the bifurcation diagram for bistability. Construction of larger synthetic circuits provides a unique opportunity for evaluating model inference, prediction, and design of complex biochemical systems and could be used to control nanoscale devices and artificial cells.

Item Type:Article
Related URLs:
URLURL TypeDescription DOIArticle CentralArticle
Kim, Jongmin0000-0002-2713-1006
Winfree, Erik0000-0002-5899-7523
Additional Information:© 2006 EMBO and Nature Publishing Group. Open Access. Received 12 July 2006; Accepted 30 August 2006; Published online 12 December 2006. We thank Y Zuo, ZF Cheng, A Malhotra, and MP Deutscher for their kind gift of RNases; KL Ho, C Wierzynski, D Stick, RM Murray, and CDS 273 students for helpful discussion on modeling; DY Zhang, S Mohanty, PWK Rothemund, G Seelig, JJ Hopfield, S Leibler, and B Yurke for discussion. Supported by ONR YIP Award No. N000140110813 and NSF ITR Award No. 0113443 to E Winfree and NSF NIRT Award No. 0103002 to N Seeman.
Funding AgencyGrant Number
Office of Naval Research (ONR) N000140110813
Subject Keywords:bistability; ultrasensitivity; design principles; dynamical systems; transcription
PubMed Central ID:PMC1762086
Record Number:CaltechAUTHORS:20110309-104200419
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:22752
Deposited By: Lucinda Acosta
Deposited On:20 Oct 2011 22:00
Last Modified:09 Nov 2021 16:07

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