Enhancing circuit stability under growth feedback with supplementary repressive regulation

Author:

Stone Austin1,Rijal Sadikshya1,Zhang Rong1,Tian Xiao-Jun1ORCID

Affiliation:

1. School of Biological and Health Systems Engineering, Arizona State University , Tempe , AZ 85281, USA

Abstract

Abstract The field of synthetic biology and biosystems engineering increasingly acknowledges the need for a holistic design approach that incorporates circuit-host interactions into the design process. Engineered circuits are not isolated entities but inherently entwined with the dynamic host environment. One such circuit-host interaction, ‘growth feedback’, results when modifications in host growth patterns influence the operation of gene circuits. The growth-mediated effects can range from growth-dependent elevation in protein/mRNA dilution rate to changes in resource reallocation within the cell, which can lead to complete functional collapse in complex circuits. To achieve robust circuit performance, synthetic biologists employ a variety of control mechanisms to stabilize and insulate circuit behavior against growth changes. Here we propose a simple strategy by incorporating one repressive edge in a growth-sensitive bistable circuit. Through both simulation and in vitro experimentation, we demonstrate how this additional repressive node stabilizes protein levels and increases the robustness of a bistable circuit in response to growth feedback. We propose the incorporation of repressive links in gene circuits as a control strategy for desensitizing gene circuits against growth fluctuations.

Funder

National Science Foundation

National Institutes of Health

Publisher

Oxford University Press (OUP)

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