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Published April 26, 2019 | Submitted + Published + Supplemental Material
Journal Article Open

Architectural Principles for Characterizing the Performance of Antithetic Integral Feedback Networks

Abstract

As we begin to design increasingly complex synthetic biomolecular systems, it is essential to develop rational design methodologies that yield predictable circuit performance. Here we apply theoretical tools from the theory of control and dynamical systems to yield practical insights into the architecture and function of a particular class of biological feedback circuit. Specifically, we show that it is possible to analytically characterize both the operating regime and performance tradeoffs of a sequestration feedback circuit architecture. Further, we demonstrate how these principles can be applied to inform the design process of a particular synthetic feedback circuit.

Additional Information

© 2019 The Author(s). Under a Creative Commons license (Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)). Received 26 September 2018, Revised 14 March 2019, Accepted 1 April 2019, Available online 8 April 2019. The authors would like to thank Harry Nunns for providing feedback on the manuscript, Anandh Swaminathan for helping with stochastic simulations, and Reed McCardell for providing insight into the synthetic growth circuit. The project was sponsored by the Defense Advanced Research Projects Agency (Agreement HR0011-17-2-0008). The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. Author Contributions: N.O. and F.X. conceived of and performed analysis, wrote the maunscript, and wrote code for simulations and figures. J.C.D. supervised the work, gave feedback on the manuscript, and and provided funding. Supplementary code is provided which was used to generate the figures in the paper. The authors declare no competing interests.

Attached Files

Published - 1-s2.0-S2589004219301014-main.pdf

Submitted - 428300.full.pdf

Supplemental Material - 1-s2.0-S2589004219301014-mmc2.zip

Supplemental Material - mmc1.pdf

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