A universal biomolecular integral feedback controller for robust perfect adaptation

Nature, Journal Year: 2019, Volume and Issue: 570(7762), P. 533 - 537

Published: June 1, 2019

Language: Английский

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Optogenetic regulation of engineered cellular metabolism for microbial chemical production

Nature, Journal Year: 2018, Volume and Issue: 555(7698), P. 683 - 687

Published: March 1, 2018

Language: Английский

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Precise, automated control of conditions for high-throughput growth of yeast and bacteria with eVOLVER

Nature Biotechnology, Journal Year: 2018, Volume and Issue: 36(7), P. 614 - 623

Published: June 11, 2018

Language: Английский

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Balancing a genetic toggle switch by real-time feedback control and periodic forcing

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Nov. 16, 2017

Abstract Cybergenetics is a novel field of research aiming at remotely pilot cellular processes in real-time with to leverage the biotechnological potential synthetic biology. Yet, control only small number genetic circuits has been tested so far. Here we investigate multistable gene regulatory networks, which are ubiquitously found nature and play critical roles cell differentiation decision-making. Using an silico feedback loop, demonstrate that bistable toggle switch can be dynamically maintained near its unstable equilibrium position for extended periods time. Importantly, show direct method based on dual periodic forcing sufficient simultaneously maintain many cells this undecided state. These findings pave way more complex decision-making systems both single population levels, vast fundamental applications.

Language: Английский

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Dynamic control in metabolic engineering: Theories, tools, and applications

Metabolic Engineering, Journal Year: 2020, Volume and Issue: 63, P. 126 - 140

Published: Sept. 11, 2020

Metabolic engineering has allowed the production of a diverse number valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow commercialization metabolically engineered systems. Dynamic metabolic is rapidly developing field that seeks to address these through design genetically encoded control systems allow cells autonomously adjust their flux in response external internal state. This review first discusses theoretical works provide mechanistic insights choices dynamic including two-stage, continuous, population behavior strategies. Next, we summarize molecular mechanisms various sensors actuators enable Finally, important applications several metabolite products are highlighted, fatty acids, aromatics, terpene compounds. Altogether, this provides comprehensive overview progress, advances, prospects improved titer, rate, yield metrics engineering.

Language: Английский

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An Optogenetic Platform for Real-Time, Single-Cell Interrogation of Stochastic Transcriptional Regulation

Molecular Cell, Journal Year: 2018, Volume and Issue: 70(4), P. 745 - 756.e6

Published: May 1, 2018

Transcription is a highly regulated and inherently stochastic process. The complexity of signal transduction gene regulation makes it challenging to analyze how the dynamic activity transcriptional regulators affects transcription. By combining fast-acting, photo-regulatable transcription factor with nascent RNA quantification in live cells an experimental setup for precise spatiotemporal delivery light inputs, we constructed platform real-time, single-cell interrogation Saccharomyces cerevisiae. We show that activation deactivation are fast memoryless. analyzing temporal individual cells, found occurs bursts, whose duration timing modulated by activity. Using our platform, via light-driven feedback loops at level. Feedback markedly reduced cell-to-cell variability led qualitative differences cellular dynamics. Our establishes flexible method studying dynamics single cells.

Language: Английский

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Dynamic Blue Light-Inducible T7 RNA Polymerases (Opto-T7RNAPs) for Precise Spatiotemporal Gene Expression Control

ACS Synthetic Biology, Journal Year: 2017, Volume and Issue: 6(11), P. 2157 - 2167

Published: Oct. 18, 2017

Light has emerged as a control input for biological systems due to its precise spatiotemporal resolution. The limited toolset light in bacteria motivated us develop light-inducible transcription system that is independent from cellular regulation through the use of an orthogonal RNA polymerase. Here, we present our engineered blue light-responsive T7 polymerases (Opto-T7RNAPs) show properties such low leakiness gene expression dark state, high strength when induced with light, and inducible range more than 300-fold. Following optimization reduce variability, created variant returns inactive state within minutes once turned off. This allows dynamic expression, which key aspect most applications using optogenetic regulation. regulators, only require ordinary light-emitting diodes induction, were developed tested bacterium Escherichia coli, crucial cell factory biotechnology fast inexpensive cultivation well understood physiology genetics. Opto-T7RNAP, minor alterations, should be extendable other bacterial species eukaryotes mammalian cells yeast polymerase Vivid regulator have been shown functional. We anticipate approach will expand applicability inducer allow reliable synthetic natural networks.

Language: Английский

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Diverse light responses of cyanobacteria mediated by phytochrome superfamily photoreceptors

Nature Reviews Microbiology, Journal Year: 2018, Volume and Issue: 17(1), P. 37 - 50

Published: Nov. 8, 2018

Language: Английский

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Bacterial co-culture with cell signaling translator and growth controller modules for autonomously regulated culture composition

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 11, 2019

Synthetic biology and metabolic engineering have expanded the possibilities for engineered cell-based systems. The addition of non-native biosynthetic regulatory components can, however, overburden reprogrammed cells. In order to avoid overload, an emerging area focus is on consortia, wherein cell subpopulations work together carry out a desired function. This strategy requires regulation populations. Here, we design synthetic co-culture controller consisting signal translator growth-controller modules that, when implemented, provide autonomous consortia composition. system co-opts orthogonal autoinducer AI-1 AI-2 cell-cell signaling mechanisms bacterial quorum sensing (QS) enable cross-talk between strains QS signal-controlled growth rate modulate relative population densities. We further develop simple mathematical model that enables closed-loop control trajectories.

Language: Английский

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Current and future modalities of dynamic control in metabolic engineering

Current Opinion in Biotechnology, Journal Year: 2018, Volume and Issue: 52, P. 56 - 65

Published: March 23, 2018

Language: Английский

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