This work used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli, which periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells.
This work constructed strains of Escherichia coli that enable detection of noise and discrimination between the two mechanisms by which it is generated and reveals how low intracellular copy numbers of molecules can fundamentally limit the precision of gene regulation.
It is found that p53 was expressed in a series of discrete pulses after DNA damage, and it is suggested that the p53-Mdm2 feedback loop generates a 'digital' clock that releases well-timed quanta of p53 until damage is repaired or the cell dies.
Proceedings of the National Academy of Sciences…
17 September 2002
TLDR
It is shown how the total variation in the level of expression of a given gene can be decomposed into its intrinsic and extrinsic components and theoretically that simultaneous measurement of two identical genes per cell enables discrimination of these two types of noise.
It is found that protein production rates fluctuate over a time scale of about one cell cycle, while intrinsic noise decays rapidly, which can form a basis for quantitative modeling of natural gene circuits and for design of synthetic ones.
Noninvasive measurements of the apparent diffusion coefficient of green fluorescent protein (GFP) in the cytoplasm of Escherichia coli have implications for the understanding of intracellular biochemical networks.
An excitable core module containing positive and negative feedback loops can explain both entry into, and exit from, the competent state of Bacillus subtilis, and is found to provide an ideal mechanism for competence regulation.
Examples and emerging principles that connect noise, the architecture of the gene circuits in which it is present, and the biological functions it enables are reviewed.
It is shown that Crz1 exhibits short bursts of nuclear localization that occur stochastically in individual cells and propagate to the expression of downstream genes, and frequency-modulation regulation of localization bursts ensures proportional expression of multiple target genes across a wide dynamic range of expression levels, independent of promoter characteristics.
Proceedings of the National Academy of Sciences…
27 July 2004
TLDR
The effect of coupling through intercell signaling in a population of Escherichia coli cells expressing a synthetic biological clock is studied to predict that a diverse and noisy community of such genetic oscillators interacting through a quorum-sensing mechanism should self-synchronize in a robust way, leading to a substantially improved global rhythmicity in the system.