期刊
ACS SYNTHETIC BIOLOGY
卷 10, 期 12, 页码 3330-3342出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.1c00281
关键词
resource competition; modular composition; experiment design
资金
- NSF Expeditions in Computing Award [1521925]
- Direct For Computer & Info Scie & Enginr
- Division of Computing and Communication Foundations [1521925] Funding Source: National Science Foundation
The design of genetic circuits must account for the impact of resource competition among modules, requiring prediction of changes in module behavior; by introducing characteristics of resource demand and sensitivity to resource loading, predictions can be made for the behavior of different genetic modules in the cell.
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 multimodule 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 library, 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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