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Loading as a design parameter for genetic circuits

Author(s)
Kumar, Nithin Senthur; Del Vecchio, Domitilla
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Abstract
A significant problem when building complex biomolecular circuits is due to context-dependence: the dynamics of a system are altered upon changes to its context, potentially degrading the system's performance. Here, we study retroactivity, a specific type of context-dependence, by analyzing the effects of loads on a transcription factor applied by the transcription factor's target sites. In particular, we study this loading effect on the model of an activator-repressor oscillator, a widely studied motif in synthetic and systems biology. Our analysis indicates that strong activation and weak repression are key for a stable limit cycle. Repression can be effectively weakened by adding load to the repressor, while activation can be effectively weakened by adding load to the activator. Therefore, loading the repressor can be employed as a design parameter to establish a stable limit cycle. In contrast, loading the activator is deleterious to the clock.
Date issued
2016-08
URI
http://hdl.handle.net/1721.1/109188
Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Journal
American Control Conference (ACC), 2016
Publisher
Institute of Electrical and Electronics Engineers (IEEE)
Citation
Kumar, Nithin Senthur and Del Vecchio, Domitilla. “Loading as a Design Parameter for Genetic Circuits.” 2016 American Control Conference (ACC) July 6-8 2016, Boston, Massachusetts, Institute of Electrical and Electronics Engineers (IEEE), August 2016
Version: Author's final manuscript
ISBN
978-1-4673-8682-1
ISSN
2378-5861

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