ArticleNucleic acids research2015
Robust, tunable genetic memory from protein sequestration combined with positive feedback.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 46 citations in OpenAlex.
- Stoichiometric balance and sustained rhythms.Journal of mathematical biology · 2026Article
- Injectisome assembly primesmBio · 2026Article
- Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Engineering coupled consortia-based biosensors for diagnostic.Nature communications · 2025Article
- Fundamental Trade-Offs in the Robustness of Biological Systems with Feedback Regulation.ACS synthetic biology · 2025Article
- BioRxToolbox: a computational framework to streamline genetic circuit design in molecular data communications.Synthetic biology (Oxford, England) · 2024Article
- Customizing cellular signal processing by synthetic multi-level regulatory circuits.Nature communications · 2023Review
- Algorithmic Programming of Sequential Logic and Genetic Circuits for Recording Biochemical Concentration in a Probiotic Bacterium.ACS synthetic biology · 2023Article
- Characterizing a Propionate Sensor inACS synthetic biology · 2023Article
- Synthetic neuromorphic computing in living cells.Nature communications · 2022Article
- A hierarchy of biomolecular proportional-integral-derivative feedback controllers for robust perfect adaptation and dynamic performance.Nature communications · 2022Article
- Article
- Model-guided design of mammalian genetic programs.Science advances · 2021Article
- Regulatory control of the Streptococcus mutans HdrRM LytTR Regulatory System functions via a membrane sequestration mechanism.Molecular microbiology · 2020Article
- Dynamical model fitting to a synthetic positive feedback circuit inEngineering biology · 2020Article
- Improvement of the memory function of a mutual repression network in a stochastic environment by negative autoregulation.BMC bioinformatics · 2019Article
- Dynamics of sequestration-based gene regulatory cascades.Nucleic acids research · 2017Article
- Hypothetical biomolecular probe based on a genetic switch with tunable symmetry and stability.BMC systems biology · 2016Article
- Programmable control of bacterial gene expression with the combined CRISPR and antisense RNA system.Nucleic acids research · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural regulatory networks contain many interacting components that allow for fine-tuning of switching and memory properties. Building simple bistable switches, synthetic biologists have learned the design principles of complex natural regulatory networks. However, most switches constructed so far are so simple (e.g. comprising two regulators) that they are functional only within a limited parameter range. Here, we report the construction of robust, tunable bistable switches in Escherichia coli using three heterologous protein regulators (ExsADC) that are sequestered into an inactive complex through a partner swapping mechanism. On the basis of mathematical modeling, we accurately predict and experimentally verify that the hysteretic region can be fine-tuned by controlling the interactions of the ExsADC regulatory cascade using the third member ExsC as a tuning knob. Additionally, we confirm that a dual-positive feedback switch can markedly increase the hysteretic region, compared to its single-positive feedback counterpart. The dual-positive feedback switch displays bistability over a 10(6)-fold range of inducer concentrations, to our knowledge, the largest range reported so far. This work demonstrates the successful interlocking of sequestration-based ultrasensitivity and positive feedback, a design principle that can be applied to the construction of robust, tunable, and predictable genetic programs to achieve increasingly sophisticated biological behaviors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.