ArticleMolecular systems biology2011
Synthetic conversion of a graded receptor signal into a tunable, reversible switch.
Article in Molecular systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Jaxkineticmodel: Neural ordinary differential equations inspired parameterization of kinetic models.PLoS computational biology · 2025Article
- An engineered protein-phosphorylation toggle network with implications for endogenous network discovery.Science (New York, N.Y.) · 2021Article
- Variable cellular decision-making behavior in a constant synthetic network topology.BMC bioinformatics · 2019Article
- Adapting machine-learning algorithms to design gene circuits.BMC bioinformatics · 2019Article
- Towards a Quantitative Understanding of Cell Identity.Trends in cell biology · 2018Review
- Identifying parameter regions for multistationarity.PLoS computational biology · 2017Article
- Identifying ultrasensitive HGF dose-response functions in a 3D mammalian system for synthetic morphogenesis.Scientific reports · 2016Article
- Molecular Buffers Permit Sensitivity Tuning and Inversion of Riboswitch Signals.ACS synthetic biology · 2016Article
- Finding the positive feedback loops underlying multi-stationarity.BMC systems biology · 2015Article
- Cooperativity to increase Turing pattern space for synthetic biology.ACS synthetic biology · 2015Article
- Article
- Tuning response curves for synthetic biology.ACS synthetic biology · 2013Article
- Architecture-dependent robustness in a class of multiple positive feedback loops.IET systems biology · 2013Article
- A synthetic biology approach to understanding cellular information processing.ACS synthetic biology · 2012Review
- A genetic bistable switch utilizing nonlinear protein degradation.Journal of biological engineering · 2012Article
- Sequestration-based bistability enables tuning of the switching boundaries and design of a latch.Molecular systems biology · 2012Article
- Robust network topologies for generating switch-like cellular responses.PLoS computational biology · 2011Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to engineer an all-or-none cellular response to a given signaling ligand is important in applications ranging from biosensing to tissue engineering. However, synthetic gene network 'switches' have been limited in their applicability and tunability due to their reliance on specific components to function. Here, we present a strategy for reversible switch design that instead relies only on a robust, easily constructed network topology with two positive feedback loops and we apply the method to create highly ultrasensitive (n(H)>20), bistable cellular responses to a synthetic ligand/receptor complex. Independent modulation of the two feedback strengths enables rational tuning and some decoupling of steady-state (ultrasensitivity, signal amplitude, switching threshold, and bistability) and kinetic (rates of system activation and deactivation) response properties. Our integrated computational and synthetic biology approach elucidates design rules for building cellular switches with desired properties, which may be of utility in engineering signal-transduction pathways.
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Registered trials
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