ArticleProceedings of the National Academy of Sciences of the United States of America2014
Engineered temperature compensation in a synthetic genetic clock.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 78 citations in OpenAlex.
- Design of CRISPRi-Based Synthetic Gene Circuits in Bacteria.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Intracellularly coupled oscillators for synthetic biology.Nature communications · 2025Review
- Temperature-Dependent Recombinase-Based Genetic Circuits.International journal of molecular sciences · 2025Article
- Mechanistic origins of temperature scaling in the early embryonic cell cycle.Nature communications · 2025Article
- Performance Prediction of Fundamental Transcriptional Programs.ACS synthetic biology · 2023Article
- Combined multiple transcriptional repression mechanisms generate ultrasensitivity and oscillations.Interface focus · 2022Article
- The context matrix: Navigating biological complexity for advanced biodesign.Frontiers in bioengineering and biotechnology · 2022Article
- Review
- Dependence of bacterial growth rate on dynamic temperature changes.IET systems biology · 2020Article
- Bayesian inference of distributed time delay in transcriptional and translational regulation.Bioinformatics (Oxford, England) · 2020Article
- Long-range temporal coordination of gene expression in synthetic microbial consortia.Nature chemical biology · 2019Article
- Spatiotemporal Dynamics of Synthetic Microbial Consortia in Microfluidic Devices.ACS synthetic biology · 2019Article
- Design and synthesis of synthetic UP elements for modulation of gene expression inSynthetic and systems biotechnology · 2019Article
- Multiscale effects of heating and cooling on genes and gene networks.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Towards an Aspect-Oriented Design and Modelling Framework for Synthetic Biology.Processes (Basel, Switzerland) · 2018Article
- Designing cell function: assembly of synthetic gene circuits for cell biology applications.Nature reviews. Molecular cell biology · 2018Review
- Biological Oscillators in Nanonetworks-Opportunities and Challenges.Sensors (Basel, Switzerland) · 2018Review
- Systems and synthetic biology approaches in understanding biological oscillators.Quantitative biology (Beijing, China) · 2018Article
- The Timing of Transcriptional Regulation in Synthetic Gene Circuits.ACS synthetic biology · 2017Article
- Incoherent Inputs Enhance the Robustness of Biological Oscillators.Cell systems · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Synthetic biology promises to revolutionize biotechnology by providing the means to reengineer and reprogram cellular regulatory mechanisms. However, synthetic gene circuits are often unreliable, as changes to environmental conditions can fundamentally alter a circuit's behavior. One way to improve robustness is to use intrinsic properties of transcription factors within the circuit to buffer against intra- and extracellular variability. Here, we describe the design and construction of a synthetic gene oscillator in Escherichia coli that maintains a constant period over a range of temperatures. We started with a previously described synthetic dual-feedback oscillator with a temperature-dependent period. Computational modeling predicted and subsequent experiments confirmed that a single amino acid mutation to the core transcriptional repressor of the circuit results in temperature compensation. Specifically, we used a temperature-sensitive lactose repressor mutant that loses the ability to repress its target promoter at high temperatures. In the oscillator, this thermoinduction of the repressor leads to an increase in period at high temperatures that compensates for the decrease in period due to Arrhenius scaling of the reaction rates. The result is a transcriptional oscillator with a nearly constant period of 48 min for temperatures ranging from 30 °C to 41 °C. In contrast, in the absence of the mutation the period of the oscillator drops from 60 to 30 min over the same temperature range. This work demonstrates that synthetic gene circuits can be engineered to be robust to extracellular conditions through protein-level modifications.
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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.