# High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits

@article{Deshpande2017HighRO,
title={High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits},
author={Abhishek Deshpande and Thomas E. Ouldridge},
journal={arXiv: Molecular Networks},
year={2017}
}
• Published 5 August 2017
• Physics
• arXiv: Molecular Networks
Retroactivity arises when the coupling of a molecular network $\mathcal{U}$ to a downstream network $\mathcal{D}$ results in signal propagation back from $\mathcal{D}$ to $\mathcal{U}$. The phenomenon represents a breakdown in modularity of biochemical circuits and hampers the rational design of complex functional networks. Considering simple models of signal-transduction architectures, we demonstrate the strong dependence of retroactivity on the properties of the upstream system, and explore…
5 Citations

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## References

SHOWING 1-10 OF 66 REFERENCES

### Modular cell biology: retroactivity and insulation

• Biology
Molecular systems biology
• 2008
Here, the effect of interconnections on the input–output dynamic characteristics of transcriptional components are studied, focusing on a property, which is called ‘retroactivity’, that plays a role analogous to non‐zero output impedance in electrical systems.

### Retroactivity controls the temporal dynamics of gene transcription.

• Biology
ACS synthetic biology
• 2013
The experimental results and mathematical formulas make it possible to predict the extent of the change in the dynamic behavior of a module after interconnection, and can be employed to both recover the predictive power of a modular approach to understand systems or as an additional design tool to shape the temporal behavior of gene transcription.

### Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity

• Biology
BMC Systems Biology
• 2011
The results indicate that within physiologically and therapeutically relevant ranges for all parameters, a targeted inhibitor can naturally induce an off-target effect via retroactivity, and support the position that characterizations should consider retroactivity as a robust potential source of off- target effects induced by kinase inhibitors and other targeted therapies.

### Retroactive Signaling in Short Signaling Pathways

• Biology
PloS one
• 2012
This paper explores the possibility of a new type of signaling called retroactive signaling, offered by the recently demonstrated property of retroactivity in signaling cascades, and predicts the characteristic ranges of the downstream protein, or of the upstream phosphatase, for which a retroactive effect can be observed on the upstream cycle variables.

### A load driver device for engineering modularity in biological networks

• Engineering
Nature Biotechnology
• 2014
A genetic device named a load driver is devised that mitigates the impact of load on circuit function, and its behavior is demonstrated in Saccharomyces cerevisiae.

### Retroactivity in the Context of Modularly Structured Biomolecular Systems

• Biology
Front. Bioeng. Biotechnol.
• 2015
By discussing the modules interconnection in natural and synthetic biomolecular systems, it is proposed that such systems should be considered as quasi-modular.

### Stochastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations.

• Biology
Proceedings of the National Academy of Sciences of the United States of America
• 2005
This work shows by using both analytical and numerical investigation that at least in one ubiquitous class of (bio)chemical-reaction mechanisms, enzymatic futile cycles, the external noise may induce a bistable oscillatory (dynamic switching) behavior that is both quantitatively and qualitatively different from what is predicted or possible deterministically.

### Cell signaling pathways as control modules: complexity for simplicity?

• D. Lauffenburger
• Biology
Proceedings of the National Academy of Sciences of the United States of America
• 2000
As biology begins to move into the “postgenomic” era, a key emerging question is how to approach the understanding of how complex biomolecular networks function as dynamical systems, with an intermediate concept suggesting a “modular” framework.