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Synthetic circuit for exact adaptation and fold-change detection

Kim, Jongmin and Khetarpal, Ishan and Sen, Shaunak and Murray, Richard M. (2014) Synthetic circuit for exact adaptation and fold-change detection. Nucleic Acids Research, 42 (9). pp. 6078-6089. ISSN 0305-1048. PMCID PMC4027175. doi:10.1093/nar/gku233.

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Biological organisms use their sensory systems to detect changes in their environment. The ability of sensory systems to adapt to static inputs allows wide dynamic range as well as sensitivity to input changes including fold-change detection, a response that depends only on fold changes in input, and not on absolute changes. This input scale invariance underlies an important strategy for search that depends solely on the spatial profile of the input. Synthetic efforts to reproduce the architecture and response of cellular circuits provide an important step to foster understanding at themolecular level. We report the bottom-up assembly of biochemical systems that show exact adaptation and fold-change detection. Using a malachite green aptamer as the output, a synthetic transcriptional circuit with the connectivity of an incoherent feed-forward loop motif exhibits pulse generation and exact adaptation. A simple mathematical model was used to assess the amplitude and duration of pulse response as well as the parameter regimes required for fold-change detection. Upon parameter tuning, this synthetic circuit exhibits fold-change detection for four successive rounds of two-fold input changes. The experimental realization of fold-change detection circuit highlights the programmability of transcriptional switches and the ability to obtain predictive dynamical systems in a cell-free environment for technological applications.

Item Type:Article
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URLURL TypeDescription CentralArticle
Kim, Jongmin0000-0002-2713-1006
Sen, Shaunak0000-0002-1412-8633
Murray, Richard M.0000-0002-5785-7481
Additional Information:© 2014 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. First published online: April 11, 2014. The authors thank Elisa Franco and Enoch Yeung for comments on the manuscript. Funding: National Science Foundation [0832824, The Molecular Programming Project]. Source of open access funding: National Science Foundation award no. 0832824 (The Molecular Programming Project). Conflict of interest statement. None declared.
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Issue or Number:9
PubMed Central ID:PMC4027175
Record Number:CaltechAUTHORS:20140421-101928940
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:45065
Deposited By: Tony Diaz
Deposited On:21 Apr 2014 22:17
Last Modified:10 Nov 2021 16:59

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