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

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 reso...

Full description

Bibliographic Details
Main Authors: McBride, Cameron D (Author), Del Vecchio, Domitilla (Author)
Format: Article
Language:English
Published: American Chemical Society (ACS), 2021-12-17T18:28:40Z.
Subjects:
Online Access:Get fulltext
LEADER 01802 am a22001693u 4500
001 138591
042 |a dc 
100 1 0 |a McBride, Cameron D  |e author 
700 1 0 |a Del Vecchio, Domitilla  |e author 
245 0 0 |a Predicting Composition of Genetic Circuits with Resource Competition: Demand and Sensitivity 
260 |b American Chemical Society (ACS),   |c 2021-12-17T18:28:40Z. 
856 |z Get fulltext  |u https://hdl.handle.net/1721.1/138591 
520 |a 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. 
546 |a en 
655 7 |a Article 
773 |t 10.1021/acssynbio.1c00281 
773 |t ACS Synthetic Biology