Oct 9, 2012

Genetic programs constructed from layered logic gates in single cells

Nature
Tae Seok MoonChristopher A Voigt

Abstract

Genetic programs function to integrate environmental sensors, implement signal processing algorithms and control expression dynamics. These programs consist of integrated genetic circuits that individually implement operations ranging from digital logic to dynamic circuits, and they have been used in various cellular engineering applications, including the implementation of process control in metabolic networks and the coordination of spatial differentiation in artificial tissues. A key limitation is that the circuits are based on biochemical interactions occurring in the confined volume of the cell, so the size of programs has been limited to a few circuits. Here we apply part mining and directed evolution to build a set of transcriptional AND gates in Escherichia coli. Each AND gate integrates two promoter inputs and controls one promoter output. This allows the gates to be layered by having the output promoter of an upstream circuit serve as the input promoter for a downstream circuit. Each gate consists of a transcription factor that requires a second chaperone protein to activate the output promoter. Multiple activator-chaperone pairs are identified from type III secretion pathways in different strains of bacteria. Directe...Continue Reading

Mentioned in this Paper

Directed Evolution
Single-Cell Analysis
Gene Expression Regulation, Bacterial
Anatomical Layer
Alkalescens-Dispar Group
Metabolic Networks
Secretory Pathway
Transcription, Genetic
Promoter
Cell Engineering

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