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Predicting Composition of Genetic Circuits with Resource Competition: Demand and Sensitivity

View ORCID ProfileCameron D. McBride, Domitilla Del Vecchio
doi: https://doi.org/10.1101/2021.05.26.445862
Cameron D. McBride
Department of Mechanical Engineering, MIT, 77 Massachusetts Ave, Cambridge, MA, USA
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Domitilla Del Vecchio
Department of Mechanical Engineering, MIT, 77 Massachusetts Ave, Cambridge, MA, USA
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  • For correspondence: ddv@mit.edu
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Abstract

The design of genetic circuits typically relies on characterization of constituent modules in isolation to predict the behavior of modules’ composition. However, it has been shown that the behavior of a genetic module changes when other modules are in the cell due to competition for shared resources. In order to engineer multi-module circuits that behave as intended, it is thus necessary to predict changes in the behavior of a genetic module when other modules load cellular resources. Here, we introduce two characteristics of circuit modules: the demand for cellular resources and the sensitivity to resource loading. When both are known for every genetic module in a circuit, they can be used to predict any module’s behavior upon addition of any other module to the cell. We develop an experimental approach to measure both characteristics for any circuit module using a resource sensor module. Using the measured resource demand and sensitivity for each module in a library, the outputs of the modules can be accurately predicted when they are inserted in the cell in arbitrary combinations. These resource competition characteristics may be used to inform the design of genetic circuits that perform as predicted despite resource competition.

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Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* E-mail: cmcbride{at}mit.edu; ddv{at}mit.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 27, 2021.
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Predicting Composition of Genetic Circuits with Resource Competition: Demand and Sensitivity
Cameron D. McBride, Domitilla Del Vecchio
bioRxiv 2021.05.26.445862; doi: https://doi.org/10.1101/2021.05.26.445862
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Predicting Composition of Genetic Circuits with Resource Competition: Demand and Sensitivity
Cameron D. McBride, Domitilla Del Vecchio
bioRxiv 2021.05.26.445862; doi: https://doi.org/10.1101/2021.05.26.445862

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