Distinct noise-controlling roles of multiple negative feedback mechanisms in a prokaryotic operon system

Nguyen, Lan K.; Kulasiri, Don

doi:10.1049/iet-syb.2010.0020

Cited by 5 publications

(3 citation statements)

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“…Negative feedbacks have been known to suppress noise [55,56], understanding the behaviour of noise in nested feedback structures is an interesting topic. In our recent work [12], we explored how noise is propagated and managed in the prokaryotic tryptophan operon system of E. coli, a model system governed by three nested negative-feedback loops. Interestingly, it was found that the individual loops in this system do not all reduce noise, but some actually enhance noise levels of the system output.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, multiple negative-feedback structures are prominent in the synthesis pathways of many common amino acids, where the amino acids regulate their own production by concurrently inhibiting multiple upstream reaction steps [9,10]. For instance, the tryptophan operon has evolved seemingly redundant negative-feedback loops, but which appear to be providing distinct dynamical and noise-related functions [11][12][13]. The cooperative feedback structures exemplified above often underline intricate connections between molecular components within cellular pathways as well as crosstalks between them.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of oscillation dynamics in biochemical systems with dual negative feedback loops

Nguyen

2012

J. R. Soc. Interface.

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Feedback controls are central to cellular regulation. Negative-feedback mechanisms are well known to underline oscillatory dynamics. However, the presence of multiple negativefeedback mechanisms is common in oscillatory cellular systems, raising intriguing questions of how they cooperate to regulate oscillations. In this work, we studied the dynamical properties of a set of general biochemical motifs with dual, nested negative-feedback structures. We showed analytically and then confirmed numerically that, in these motifs, each negativefeedback loop exhibits distinctly different oscillation-controlling functions. The longer, outer feedback loop was found to promote oscillations, whereas the short, inner loop suppresses and can even eliminate oscillations. We found that the position of the inner loop within the coupled motifs affects its repression strength towards oscillatory dynamics. Bifurcation analysis indicated that emergence of oscillations may be a strict parametric requirement and thus evolutionarily tricky. Investigation of the quantitative features of oscillations (i.e. frequency, amplitude and mean value) revealed that coupling negative feedback provides robust tuning of the oscillation dynamics. Finally, we demonstrated that the mitogen-activated protein kinase (MAPK) cascades also display properties seen in the general nested feedback motifs. The findings and implications in this study provide novel understanding of biochemical negative-feedback regulation in a mixed wiring context.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of oscillation dynamics in biochemical systems with dual negative feedback loops

Nguyen

2012

J. R. Soc. Interface.

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“…Furthermore, it is known that negative feedback is the most common noise-attenuation regulatory mechanism. For example, Becskei and Serrano (2000) and Thattai and Oudenaarden (2001) demonstrated that negative feedback decreases the noise level in gene circuits with one Nguyen and Kulasiri (2011) demonstrated that the feedback loops of the trp operon of E. coli possess distinct, even opposing noise-controlling effects. Finally, while the enzymes and pathway of tryptophan biosynthesis are identical in B. subtilis and E. coli, the operon organizations differ in these bacteria: the number of feedback loops is different, as are the regulatory molecular mechanisms .…”

Section: Introductionmentioning

confidence: 99%