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...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/89170 |
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| 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 |