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Design of a genetic layered feedback controller in synthetic biological circuitry

Hu, Chelsea Y. and Murray, Richard M. (2019) Design of a genetic layered feedback controller in synthetic biological circuitry. . (Unpublished)

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Feedback control is the key to achieve robust performances for many engineered systems. However, its application in biological contexts is still largely unexplored. In this work, we designed, analyzed and simulated a layered controller functioning at both molecular and populational levels. First, we used a minimal model of three states to represent a system where state A activates state B; state R is a by-product of state B that acts as a negative feedback regulating both state A, B, and sequentially R. We call the feedback applied to state B a cis feedback and the one applied to state A a trans feedback. Through stability analysis via linearization at equilibrium and sensitivity analysis at transient state, we found that the cis feedback attenuates disturbances better but recovers slower; the trans feedback recovers faster but has more dramatic responses to fluctuations; the layered feedback demonstrates both advantageous traits of the two single layers. Then we designed two versions of synthetic genetic circuits to implement the layered controller in living cells. One version with an sRNA as regulator R, the other with a transcription factor protein as the regulator R. The analysis and dynamical simulation of the models confirmed the analytical results from the minimal model. At the same time, we found that the protein regulated feedback controls have faster recovery speed but the RNA version has a stronger disturbance attenuation effect.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Hu, Chelsea Y.0000-0002-2211-1778
Murray, Richard M.0000-0002-5785-7481
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. bioRxiv preprint first posted online May. 24, 2019. The authors would like to thank Reed McCardell, Ayush Pandey and Xinying Ren for their insightful discussions. The author C. Y. Hu is supported by 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.
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Record Number:CaltechAUTHORS:20190528-093001677
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Official Citation:Design of a genetic layered feedback controller in synthetic biological circuitry. Chelsea Y. Hu, Richard M. Murray. bioRxiv 647057; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95810
Deposited By: Tony Diaz
Deposited On:28 May 2019 16:36
Last Modified:03 Oct 2019 21:16

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