Dynamical mechanisms of growth-feedback effects on adaptive gene circuits

The successful integration of engineered gene circuits into host cells remains a significant challenge in synthetic biology due to circuit–host interactions, such as growth feedback, where the circuit influences cell growth and vice versa. Understanding the dynamics of circuit failures and identifyi...

Full description

Saved in:
Bibliographic Details
Main Authors: Ling-Wei Kong, Wenjia Shi, Xiao-Jun Tian, Ying-Cheng Lai
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/89170
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850233216668008448
author Ling-Wei Kong
Wenjia Shi
Xiao-Jun Tian
Ying-Cheng Lai
author_facet Ling-Wei Kong
Wenjia Shi
Xiao-Jun Tian
Ying-Cheng Lai
author_sort Ling-Wei Kong
collection DOAJ
description The successful integration of engineered gene circuits into host cells remains a significant challenge in synthetic biology due to circuit–host interactions, such as growth feedback, where the circuit influences cell growth and vice versa. Understanding the dynamics of circuit failures and identifying topologies resilient to growth feedback are crucial for both fundamental and applied research. Utilizing transcriptional regulation circuits with adaptation as a paradigm, we systematically study more than 400 topological structures and uncover various categories of failures. Three dynamical mechanisms of circuit failures are identified: continuous deformation of the response curve, strengthened or induced oscillations, and sudden switching to coexisting attractors. Our extensive computations also uncover a scaling law between a circuit robustness measure and the strength of growth feedback. Despite the negative effects of growth feedback on the majority of circuit topologies, we identify several circuits that maintain optimal performance as designed, a feature important for applications.
format Article
id doaj-art-88c64fcd346942bcb97d9500e19c1908
institution OA Journals
issn 2050-084X
language English
publishDate 2025-06-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj-art-88c64fcd346942bcb97d9500e19c19082025-08-20T02:02:58ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011210.7554/eLife.89170Dynamical mechanisms of growth-feedback effects on adaptive gene circuitsLing-Wei Kong0https://orcid.org/0000-0002-8921-1642Wenjia Shi1Xiao-Jun Tian2Ying-Cheng Lai3https://orcid.org/0000-0002-0723-733XSchool of Electrical, Computer and Energy Engineering, Arizona State University, Tempe, United StatesDepartment of Physics, Xi’an University of Technology, Xi'an, ChinaSchool of Biological and Health Systems Engineering, Arizona State University, Tempe, United StatesSchool of Electrical, Computer and Energy Engineering, Arizona State University, Tempe, United States; Department of Physics, Arizona State University, Tempe, United StatesThe successful integration of engineered gene circuits into host cells remains a significant challenge in synthetic biology due to circuit–host interactions, such as growth feedback, where the circuit influences cell growth and vice versa. Understanding the dynamics of circuit failures and identifying topologies resilient to growth feedback are crucial for both fundamental and applied research. Utilizing transcriptional regulation circuits with adaptation as a paradigm, we systematically study more than 400 topological structures and uncover various categories of failures. Three dynamical mechanisms of circuit failures are identified: continuous deformation of the response curve, strengthened or induced oscillations, and sudden switching to coexisting attractors. Our extensive computations also uncover a scaling law between a circuit robustness measure and the strength of growth feedback. Despite the negative effects of growth feedback on the majority of circuit topologies, we identify several circuits that maintain optimal performance as designed, a feature important for applications.https://elifesciences.org/articles/89170synthetic gene circuitshost effectsgrowth feedbackbiological network designgene network topologyadaptive response
spellingShingle Ling-Wei Kong
Wenjia Shi
Xiao-Jun Tian
Ying-Cheng Lai
Dynamical mechanisms of growth-feedback effects on adaptive gene circuits
eLife
synthetic gene circuits
host effects
growth feedback
biological network design
gene network topology
adaptive response
title Dynamical mechanisms of growth-feedback effects on adaptive gene circuits
title_full Dynamical mechanisms of growth-feedback effects on adaptive gene circuits
title_fullStr Dynamical mechanisms of growth-feedback effects on adaptive gene circuits
title_full_unstemmed Dynamical mechanisms of growth-feedback effects on adaptive gene circuits
title_short Dynamical mechanisms of growth-feedback effects on adaptive gene circuits
title_sort dynamical mechanisms of growth feedback effects on adaptive gene circuits
topic synthetic gene circuits
host effects
growth feedback
biological network design
gene network topology
adaptive response
url https://elifesciences.org/articles/89170
work_keys_str_mv AT lingweikong dynamicalmechanismsofgrowthfeedbackeffectsonadaptivegenecircuits
AT wenjiashi dynamicalmechanismsofgrowthfeedbackeffectsonadaptivegenecircuits
AT xiaojuntian dynamicalmechanismsofgrowthfeedbackeffectsonadaptivegenecircuits
AT yingchenglai dynamicalmechanismsofgrowthfeedbackeffectsonadaptivegenecircuits