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Layered feedback control overcomes performance trade-off in synthetic biomolecular networks

Hu, Chelsea Y. and Murray, Richard M. (2022) Layered feedback control overcomes performance trade-off in synthetic biomolecular networks. Nature Communications, 13 . Art. No. 5393. ISSN 2041-1723. PMCID PMC9474519. doi:10.1038/s41467-022-33058-6.

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AbstractLayered feedback is an optimization strategy in feedback control designs widely used in engineering. Control theory suggests that layering multiple feedbacks could overcome the robustness-speed performance trade-off limit. In natural biological networks, genes are often regulated in layers to adapt to environmental perturbations. It is hypothesized layering architecture could also overcome the robustness-speed performance trade-off in genetic networks. In this work, we validate this hypothesis with a synthetic biomolecular network in living E. coli cells. We start with system dynamics analysis using models of various complexities to guide the design of a layered control architecture in living cells. Experimentally, we interrogate system dynamics under three groups of perturbations. We consistently observe that the layered control improves system performance in the robustness-speed domain. This work confirms that layered control could be adopted in synthetic biomolecular networks for performance optimization. It also provides insights into understanding genetic feedback control architectures in nature.

Item Type:Article
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URLURL TypeDescription CentralArticle ItemDiscussion Paper
Hu, Chelsea Y.0000-0002-2211-1778
Murray, Richard M.0000-0002-5785-7481
Additional Information:The authors would like to thank John Doyle, Fangzhou Xiao, Ayush Pandey, and Xinying Ren for their insightful discussions, as well as John Doyle, John Marken, and Ayush Pandey for their feedback on the manuscript. The author C.Y.H. is partially supported by Defense Advanced Research Projects Agency (Agreement HR0011-17-2-0008 - R.M.M.). The content of the information does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred.
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
PubMed Central ID:PMC9474519
Record Number:CaltechAUTHORS:20221003-756400000.10
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:117204
Deposited By: Melissa Ray
Deposited On:04 Oct 2022 22:16
Last Modified:04 Oct 2022 22:16

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