ArticleNature communications2022
Robust and tunable signal processing in mammalian cells via engineered covalent modification cycles.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- GenAI-Net: A generative AI framework for automated biomolecular network design.Science advances · 2026Article
- Programmable promoter editing for precise control of transgene expression.Nature biotechnology · 2026Article
- Resource Competition and Growth Dilution Modulate Synthetic Gene Cascade Dynamics.ACS synthetic biology · 2026Article
- From Negative Feedback to Integrated Control: Recombinase-Based Strategies for Mitigating Resource Competition.Methods in molecular biology (Clifton, N.J.) · 2026Article
- CRISPRi-Linked Multimodule Negative Feedback Loops to Address Winner-Take-All Resource Competition.ACS synthetic biology · 2025Article
- Integrating recombinase-based feedback and feedforward control for optimal resource decoupling.Nucleic acids research · 2025Article
- Synthetic Forms Most Beautiful: Engineering Insights into Self-Organization.Physiology (Bethesda, Md.) · 2025Review
- CRISPRi-Linked Multi-Module Negative Feedback Loops to Address Winner-Take-All Resource Competition.bioRxiv : the preprint server for biology · 2025Article
- Resource competition-driven bistability and stochastic switching amplify gene expression noise.PLoS computational biology · 2025Article
- Mitigating Winner-Take-All Resource Competition through Antithetic Control Mechanism.ACS synthetic biology · 2024Article
- Noise Reduction in Resource-Coupled Multi-Module Gene Circuits through Antithetic Feedback Control.Proceedings of the ... IEEE Conference on Decision & Control. IEEE Conference on Decision & Control · 2024Article
- Engineering signalling pathways in mammalian cells.Nature biomedical engineering · 2024Review
- Programmable promoter editing for precise control of transgene expression.bioRxiv : the preprint server for biology · 2024Article
- Context-dependent redesign of robust synthetic gene circuits.Trends in biotechnology · 2024Review
- Customizing cellular signal processing by synthetic multi-level regulatory circuits.Nature communications · 2023Review
- Engineering synthetic phosphorylation signaling networks in human cells.bioRxiv : the preprint server for biology · 2023Article
- Article
- Growth Feedback Confers Cooperativity in Resource-Competing Synthetic Gene Circuits.Chaos, solitons, and fractals · 2023Article
- Feedforward growth rate control mitigates gene activation burden.Nature communications · 2022Article
- Context-aware synthetic biology by controller design: Engineering the mammalian cell.Cell systems · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engineered signaling networks can impart cells with new functionalities useful for directing differentiation and actuating cellular therapies. For such applications, the engineered networks must be tunable, precisely regulate target gene expression, and be robust to perturbations within the complex context of mammalian cells. Here, we use bacterial two-component signaling proteins to develop synthetic phosphoregulation devices that exhibit these properties in mammalian cells. First, we engineer a synthetic covalent modification cycle based on kinase and phosphatase proteins derived from the bifunctional histidine kinase EnvZ, enabling analog tuning of gene expression via its response regulator OmpR. By regulating phosphatase expression with endogenous miRNAs, we demonstrate cell-type specific signaling responses and a new strategy for accurate cell type classification. Finally, we implement a tunable negative feedback controller via a small molecule-stabilized phosphatase, reducing output expression variance and mitigating the context-dependent effects of off-target regulation and resource competition. Our work lays the foundation for establishing tunable, precise, and robust control over cell behavior with synthetic signaling networks.
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Registered trials
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.