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| Open AccessDeciphering driver regulators of cell fate decisions from single-cell transcriptomics data with CEFCON
Deciphering the roles of gene regulation in cell fate decisions is crucial. Here, authors present CEFCON, a network-based framework that reveals cell-lineage-specific gene regulatory networks and identifies driver regulators controlling cell fate decisions from single-cell transcriptomics data.
- Peizhuo Wang
- , Xiao Wen
- & Jianyang Zeng
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Article
| Open AccessUniversal structures for adaptation in biochemical reaction networks
At the molecular level, the evolution of life is driven by the generation and diversification of adaptation mechanisms. Here Araujo and Liotta identify definitive and universal structural requirements for adaptation via intermolecular interactions.
- Robyn P. Araujo
- & Lance A. Liotta
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Article
| Open AccessA cybergenetic framework for engineering intein-mediated integral feedback control systems
Homeostasis and robust perfect adaptation are remarkable features of living cells. Here, to synthetically achieve this, the authors present a theoretical and experimental framework using inteins to implement compact biomolecular integral feedback controllers.
- Stanislav Anastassov
- , Maurice Filo
- & Mustafa Khammash
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Article
| Open AccessFeedforward growth rate control mitigates gene activation burden
Heterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here the authors present a tunable, modular, and portable feedforward controller that allows dynamic modulation of a genes expression to possibly high-levels without substantially affecting growth rate.
- Carlos Barajas
- , Hsin-Ho Huang
- & Domitilla Del Vecchio
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Article
| Open AccessLayered feedback control overcomes performance trade-off in synthetic biomolecular networks
Layered feedback is an optimization strategy in feedback control designs widely used in engineering. Here, combining simulation and experimentation, the authors apply layered control - a powerful optimization strategy in engineering - to synthetic biomolecular networks in living bacteria to show layered control overcomes performance trade-offs in biology.
- Chelsea Y. Hu
- & Richard M. Murray
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Article
| Open AccessRobust and tunable signal processing in mammalian cells via engineered covalent modification cycles
Phosphorylation networks are frequently at the heart of complex cellular decision making. Here the authors engineer synthetic phosphorylation devices with feedback regulation in mammalian cells and demonstrate how to use these to achieve tunable and robust control of cell behaviours.
- Ross D. Jones
- , Yili Qian
- & Ron Weiss
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Article
| Open AccessA light tunable differentiation system for the creation and control of consortia in yeast
Artificial microbial consortia use division-of-labour to optimize production. Here the authors develop an optogenetic differentiation system in yeast to generate consortia from a single strain with tunable composition.
- Chetan Aditya
- , François Bertaux
- & Jakob Ruess
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Article
| Open AccessRapid prototyping and design of cybergenetic single-cell controllers
Practical implementation of genetic circuits is difficult due to low predictability and time-intensive troubleshooting. Here the authors present Cyberloop, which interfaces a computer with single cells to enable cell-in-the-loop testing and optimization of circuit designs before they are built.
- Sant Kumar
- , Marc Rullan
- & Mustafa Khammash
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| Open AccessThe basis of easy controllability in Boolean networks
Boolean networks allow a simplified representation of interactions. Here, the authors systematically analyze regulation in dozens of biological Boolean networks, finding mathematical regularities that suggest biological systems could be controlled through a relatively small number of components.
- Enrico Borriello
- & Bryan C. Daniels
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Article
| Open AccessAutomatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control
It is difficult to synchronize the cell cycle in a population of yeast cells for extended periods of time. Here the authors use a cybergenetic system with inbuilt feedback to synchronize a population of modified yeast.
- Giansimone Perrino
- , Sara Napolitano
- & Diego di Bernardo
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Article
| Open AccessdCas9 regulator to neutralize competition in CRISPRi circuits
CRISPRi allows for the simultaneous control of many genes, however the sgRNAs compete for binding to dCas9. Here the authors design a dCas9 concentration regulator to allow independent regulation of multiple genes.
- Hsin-Ho Huang
- , Massimo Bellato
- & Domitilla Del Vecchio
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Article
| Open AccessIn vitro implementation of robust gene regulation in a synthetic biomolecular integral controller
Feedback mechanisms for synthetic gene circuits are necessary to provide robustness to external perturbations. Here the authors validate a biomolecular controller based on a sigma and anti-sigma factor to achieve stable gene expression in the face of external disturbances in an in vitro synthetic gene circuit.
- Deepak K. Agrawal
- , Ryan Marshall
- & Eduardo D Sontag
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Article
| Open AccessIrrelevance of linear controllability to nonlinear dynamical networks
Linear controllability theories have stimulated research on control of complex networks. Here the authors investigate the concordance between linear and nonlinear approaches in ranking the importance of nodes in nonlinear networks, and conclude that linear controllability may not be applicable.
- Junjie Jiang
- & Ying-Cheng Lai
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Article
| Open AccessCycles of external dependency drive evolution of avian carotenoid networks
The mechanisms that accommodate variable external dependencies in evolution are not clear. Here, the authors show that switches between external and internal metabolic controls of carotenoid-producing networks in birds are linked to shifts in evolutionary rates, with internalization of control resulting in bursts of evolutionary diversification.
- Alexander V. Badyaev
- , Alexander B. Posner
- & Dawn M. Higginson
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Article
| Open AccessA theoretical framework for controlling complex microbial communities
Controlling microbial communities could help restore ecosystems and maintain healthy microbiota. Here, the authors introduce the notion of structural accessibility and develop a framework to identify minimal sets of driver species, manipulation of which could allow control of a microbial community.
- Marco Tulio Angulo
- , Claude H. Moog
- & Yang-Yu Liu
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Article
| Open AccessA quasi-integral controller for adaptation of genetic modules to variable ribosome demand
Competition for shared cellular resources often renders genetic circuits poorly predictable. Here the authors design a biomolecular quasi-integral controller that allows gene expression to adapt to variable demand in translation resources.
- Hsin-Ho Huang
- , Yili Qian
- & Domitilla Del Vecchio
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Article
| Open AccessBalancing a genetic toggle switch by real-time feedback control and periodic forcing
Cybergenetics aims to monitor and regulate cellular processes in real-time using computer monitoring and feedback of biological readouts. Here the authors use a feedback loop and periodic forcing to maintain cells with a bistable synthetic circuit near its unstable state.
- Jean-Baptiste Lugagne
- , Sebastián Sosa Carrillo
- & Pascal Hersen