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Negative autoregulation matches production and demand in synthetic transcriptional networks
Abstract We propose a negative feedback architectur …
We propose a negative feedback architecture that regulates activity of artificial genes, or "genelets", to meet their output downstream demand, achieving robustness with respect to uncertain open-loop output production rates. In particular, we consider the case where the outputs of two genelets interact to form a single assembled product. We show with analysis and experiments that negative autoregulation matches the production and demand of the outputs: the magnitude of the regulatory signal is proportional to the error between the circuit output concentration and its actual demand. This two-device system is experimentally implemented using in vitro transcriptional networks, where reactions are systematically designed by optimizing nucleic acid sequences with publicly available software packages. We build a predictive ordinary differential equation (ODE) model that captures the dynamics of the system, and can be used to numerically assess the scalability of this architecture to larger sets of interconnected genes. Finally, with numerical simulations we contrast our negative autoregulation scheme with a cross-activation architecture, which is less scalable and results in slower response times.
able and results in slower response times.  +
Authors Elisa Franco, Giulia Giordano, Per-Ola Forsberg, Richard M. Murray  +
Funding Biomolecular Circuits for Rapid Detection and Response to Environmental Events + , Molecular Programming Project +
ID 2013k  +
Source Submitted, ACS Synthetic Biology (4 Oct 2013)  +
Tag fgfm13-acs-synbio  +
Title Negative autoregulation matches production and demand in synthetic transcriptional networks +
Type Preprint (bioRxiv)  +
Categories Papers
Modification date
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15 May 2016 06:15:07  +
URL
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http://biorxiv.org/content/early/2013/11/14/000430  +
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Negative autoregulation matches production and demand in synthetic transcriptional networks + Title
 

 

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