A synthetic oscillatory network of transcriptional regulators

@article{Elowitz2000ASO,
  title={A synthetic oscillatory network of transcriptional regulators},
  author={Michael B. Elowitz and Stanislas Leibler},
  journal={Nature},
  year={2000},
  volume={403},
  pages={335-338}
}
Networks of interacting biomolecules carry out many essential functions in living cells, but the ‘design principles’ underlying the functioning of such intracellular networks remain poorly understood, despite intensive efforts including quantitative analysis of relatively simple systems. Here we present a complementary approach to this problem: the design and construction of a synthetic network to implement a particular function. We used three transcriptional repressor systems that are not part… 
Timing molecular motion and production with a synthetic transcriptional clock
TLDR
An “insulator circuit” was developed, which strongly reduced the detrimental influence of the load on the oscillator circuit, which will be critical for the synthesis of larger and more complex systems.
Synthetic in vitro transcriptional oscillators
TLDR
In this study, design and experimentally demonstrate three transcriptional oscillators in vitro that provide a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes to produce and degrade RNA signals.
Control of Repressilators’ oscillatory behavior by transcription cooperativityand RNA/protein time scales
TLDR
The goal is revealing general principles of cellular regulation by studying various artificial networks by means of highly simplified models and demonstrating qualitative agreement between models and experiments.
Transcription factor networks, synthetic gene expression switches, and chaotic cell-cycle oscillations
TLDR
Taking the equations previously developed to describe the cell cycle of the African tree frog Xenopus laevis and adding a spatial component, it is discovered that these equations are susceptible to chaotic behavior, and a novel design principle is established whereby the widely conserved post-fertilization calcium wave initiates and ensures synchrony of cellular divisions.
Synchronizing genetic relaxation oscillators by intercell signaling
The ability to design and construct synthetic gene regulatory networks offers the prospect of studying issues related to cellular function in a simplified context; such networks also have many
A synthetic gene–metabolic oscillator
TLDR
This work designed and constructed a synthetic circuit in Escherichia coli K12, using glycolytic flux to generate oscillation through the signalling metabolite acetyl phosphate, and demonstrates the possibility of using metabolic flux as a control factor in system-wide oscillation, as well as the predictability of a de novo gene–metabolic circuit designed using nonlinear dynamic analysis.
Dynamical modelling of feedback gene regulatory networks
TLDR
It has been revealed that the multiple negative feedback loops employed by the tryptophan operon are not redundant and have evolved to concertedly give rise to a much more efficient, adaptive and stable system, than any single mechanism would provide.
Reliability of Transcriptional Cycles and the Yeast Cell-Cycle Oscillator
TLDR
A continuous-time Boolean model is constructed of the transcriptional oscillator in yeast, which permits the modeling of noise through small fluctuations in the timing of events, and shows that it can sustain stable oscillations.
Model-driven designs of an oscillating gene network.
TLDR
Simulating the designed lac-tet-ara gene network using a hybrid stochastic-discrete and stochastically-continuous algorithm, this work seeks to elucidate the relationship between the strength and type of specific connections in the gene network and the oscillatory nature of the protein product.
Cell-cycle-synchronized, oscillatory expression of a negatively autoregulated gene in E. coli
TLDR
The results show that cell-cycle effects must be accounted for in accurate, predictive models for even simple gene circuits, andCell-cycle-periodic expression of {\lambda} Cro also suggests an explanation for cell-size dependence in lysis probability and an evolutionary basis for site-specific {\ lambda} integration.
...
...

References

SHOWING 1-10 OF 21 REFERENCES
Biochemical oscillations and cellular rhythms
TLDR
A model for circadian oscillations in the Drosophila period protein (PER) is proposed, which combines the periodic synthesis and relay of camp signals in Dictyostelium with the mitotic oscillator driving the cell division cycle.
Molecular Bases for Circadian Clocks
It's a noisy business! Genetic regulation at the nanomolar scale.
Circadian Rhythms in Rapidly Dividing Cyanobacteria
TLDR
The long-standing supposition that the biological clock cannot function in cells that divide more rapidly than the circadian cycle was investigated and some messenger RNAs showed a circadian rhythm in abundance during continuous exponential growth.
Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements.
TLDR
Controlling the expression of the genes encoding luciferase, the low abundance E.coli protein DnaJ and restriction endonuclease Cfr9I not only demonstrates that high levels of expression can be achieved but also suggests that under conditions of optimal repression only around one mRNA every 3rd generation is produced.
Biological rhythms: Circadian clocks limited by noise
TLDR
It is proposed that the ability to resist such perturbations imposes strict constraints on the oscillation mechanisms underlying circadian periodicity in vivo.
Protein molecules as computational elements in living cells
Many proteins in living cells appear to have as their primary function the transfer and processing of information, rather than the chemical transformation of metabolic intermediates or the building
Protein Design: A Hierarchic Approach
The de novo design of peptides and proteins has recently emerged as an approach for investigating protein structure and function. Designed, helical peptides provide model systems for dissecting and
Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH).
TLDR
It is shown that the ATP-dependent zinc protease HflB (FtsH) is involved in the degradation of four unstable derivatives of the amino-terminal domain of the lambdacI repressor: three with nonpolar pentapeptide tails and one with the SsrA tag (cI-SsrA).
...
...