Journal
NATURE BIOTECHNOLOGY
Volume 32, Issue 12, Pages 1268-U141Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.3044
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Funding
- Eni-MIT Energy Research Fellowship
- National Science Foundation (NSF) [DGE-1122374]
- NSF [CCF-1058127]
- NSF SynBERC [SA5284-11210]
- USAFOSR [FA9550-12-1-0129]
- USARO ICB [W911NF-09-D-0001]
- US National Institutes of Health [P50 GM098792]
- Direct For Biological Sciences [1330914] Funding Source: National Science Foundation
- Direct For Computer & Info Scie & Enginr
- Division of Computing and Communication Foundations [0964646, 1058127] Funding Source: National Science Foundation
- Div Of Molecular and Cellular Bioscience [1330914] Funding Source: National Science Foundation
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The behavior of gene modules in complex synthetic circuits is often unpredictable(1-4). 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.
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