Retroactivity Controls the Temporal Dynamics of Gene Transcription
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Author(s)
Jayanthi, Shridhar
Nilgiriwala, Kayzad
Del Vecchio, Domitilla
Date Issued
August 2013
Journal
ACS Synthetic Biology
Publisher
American Chemical Society (ACS)
Citation
Jayanthi, Shridhar et al. “Retroactivity Controls the Temporal Dynamics of Gene Transcription.” ACS Synthetic Biology 2, 8 (March 2013): 431–441 © 2013 American Chemical Society
Version
Author's final manuscript
Abstract
Just like in many engineering systems, impedance-like effects, called retroactivity, arise at the interconnection of biomolecular circuits, leading to unexpected changes in a circuit's behavior. In this paper, we provide a combined experimental and theoretical study to characterize the effects of retroactivity on the temporal dynamics of a gene transcription module in vivo. The response of the module to an inducer was measured both in isolation and when the module was connected to downstream clients. The connected module, when compared to the isolated module, responded selectively to the introduction of the inducer versus its withdrawal. Specifically, a "sign-sensitive delay" appeared, in which the connected module displayed a time delay in the response to induction and anticipation in the response to de-induction. The extent of these effects can be made larger by increasing the amounts of downstream clients and/or their binding affinity to the output protein of the module. Our experimental results and mathematical formulas make it possible to predict the extent of the change in the dynamic behavior of a module after interconnection. They can be employed to both recover the predictive power of a modular approach to understand systems or as an additional design tool to shape the temporal behavior of gene transcription. Keywords: control systems; dynamic response; modularity; retroactivity; synthetic biology
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1021/SB300098W
