ArticleNucleic acids research2010
A synthetic low-frequency mammalian oscillator.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 95 citations in OpenAlex.
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- Sequence-Based Protein Design: A Review of Using Statistical Models to Characterize Coevolutionary Traits for Developing Hybrid Proteins as Genetic Sensors.International journal of molecular sciences · 2024Review
- Design of Oscillatory Networks through Post-Translational Control of Network Components.Synthetic biology and engineering · 2023Article
- A nested bistable module within a negative feedback loop ensures different types of oscillations in signaling systems.Scientific reports · 2023Article
- Network design principle for robust oscillatory behaviors with respect to biological noise.eLife · 2022Article
- Control-Based Continuation: A New Approach to Prototype Synthetic Gene Networks.ACS synthetic biology · 2022Article
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- Using Models to (Re-)Design Synthetic Circuits.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Designing cell function: assembly of synthetic gene circuits for cell biology applications.Nature reviews. Molecular cell biology · 2018Review
- Homogeneous Time Constants Promote Oscillations in Negative Feedback Loops.ACS synthetic biology · 2018Article
- 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
- Computing with biological switches and clocks.Natural computing · 2018Article
- Incoherent Inputs Enhance the Robustness of Biological Oscillators.Cell systems · 2017Article
- Mammalian synthetic biology for studying the cell.The Journal of cell biology · 2017Review
- Systems Biology-Derived Discoveries of Intrinsic Clocks.Frontiers in neurology · 2017Review
- Integrative systems and synthetic biology of cell-matrix adhesion sites.Cell adhesion & migration · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circadian clocks have long been known to be essential for the maintenance of physiological and behavioral processes in a variety of organisms ranging from plants to humans. Dysfunctions that subvert gene expression of oscillatory circadian-clock components may result in severe pathologies, including tumors and metabolic disorders. While the underlying molecular mechanisms and dynamics of complex gene behavior are not fully understood, synthetic approaches have provided substantial insight into the operation of complex control circuits, including that of oscillatory networks. Using iterative cycles of mathematical model-guided design and experimental analyses, we have developed a novel low-frequency mammalian oscillator. It incorporates intronically encoded siRNA-based silencing of the tetracycline-dependent transactivator to enable the autonomous and robust expression of a fluorescent transgene with periods of 26 h, a circadian clock-like oscillatory behavior. Using fluorescence-based time-lapse microscopy of engineered CHO-K1 cells, we profiled expression dynamics of a destabilized yellow fluorescent protein variant in single cells and real time. The novel oscillator design may enable further insights into the system dynamics of natural periodic processes as well as into siRNA-mediated transcription silencing. It may foster advances in design, analysis and application of complex synthetic systems in future gene therapy initiatives.
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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.