Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset
| Autor: | Jose Alberto de la Paz, Rey P Dimas, Faruck Morcos, Clement T Y Chan, Xian-Li Jiang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Distributed computing
Biology Network topology Ligands Protein Engineering 03 medical and health sciences 0302 clinical medicine Protein Domains Genetics Gene Regulatory Networks Set (psychology) 030304 developmental biology 0303 health sciences Signal processing Stochastic Processes Models Statistical Bacteria Models Genetic business.industry SIGNAL (programming language) Computational Biology Signal Processing Computer-Assisted Modular design Kinetics ROC Curve Environmental sensing Synthetic Biology State (computer science) business Synthetic Biology and Bioengineering Reset (computing) 030217 neurology & neurosurgery Algorithms Allosteric Site Plasmids Protein Binding Signal Transduction Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Engineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs. Our predictions accurately agree with the performance of 40 engineered repressors. We have harnessed this framework to develop a system of multiple toggle switches with a master OFF signal that produces a unique behavior: each engineered biological activity is switched to a stable ON state by different chemicals and returned to OFF in response to a common signal. One promising application of this design is to develop living diagnostics for monitoring multiple parameters in complex physiological environments and it represents one of many circuit topologies that can be explored with modular repressors designed with coevolutionary information. |
| Databáze: | OpenAIRE |
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