A load driver device for engineering modularity in biological networks

Including a load driver in a modular genetic circuit abrogates the effect of downstream elements that can interfere with circuit performance. The behavior of gene modules in complex synthetic circuits is often unpredictable 1 , 2 , 3 , 4 . After joining modules to create a circuit, downstream elemen...

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Bibliographic Details
Published in:Nature biotechnology 2014-12, Vol.32 (12), p.1268-1275
Main Authors: Mishra, Deepak, Rivera, Phillip M, Lin, Allen, Del Vecchio, Domitilla, Weiss, Ron
Format: Article
Language:English
Subjects:
631/553/2691
631/553/2704
631/553/552
96/31
96/35
96/44
Agriculture
Binding Sites
Bioinformatics
Biology
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Brewer's yeast
Gene expression
Gene Regulatory Networks
Genes
Genetic aspects
Genetic research
letter
Life Sciences
Microbiological research
Models, Theoretical
Modularity
Molecular Sequence Data
Neurons
Regulatory Sequences, Nucleic Acid
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
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Summary:Including a load driver in a modular genetic circuit abrogates the effect of downstream elements that can interfere with circuit performance. The behavior of gene modules in complex synthetic circuits is often unpredictable 1 , 2 , 3 , 4 . After joining modules to create a circuit, downstream elements (such as binding sites for a regulatory protein) apply a load to upstream modules that can negatively affect circuit function 1 , 5 . Here we devised a genetic device named a load driver that mitigates the impact of load on circuit function, and we demonstrate its behavior in Saccharomyces cerevisiae . The load driver implements the design principle of timescale separation: inclusion of the load driver's fast phosphotransfer processes restores the capability of a slower transcriptional circuit to respond to time-varying input signals even in the presence of substantial load. Without the load driver, we observed circuit behavior that suffered from a 76% delay in response time and a 25% decrease in system bandwidth due to load. With the addition of a load driver, circuit performance was almost completely restored. Load drivers will serve as fundamental building blocks in the creation of complex, higher-level genetic circuits.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt.3044