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

  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},
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… 

Optimizing enzymatic catalysts for rapid turnover of substrates with low enzyme sequestration

This article analyses the mechanism of enzyme-substrate catalysis from the perspective of minimizing the load on the enzymes through sequestration, while maintaining at least a minimum reaction flux and finds that the optimal design will saturate the bound on the minimal flux and reflects a basic trade-off in catalytic operation.

Implementing Non-Equilibrium Networks with Active Circuits of Duplex Catalysts

This work proposes a new framework for constructing catalytic DSD networks: Active Circuits of Duplex Catalysts (ACDC), and analyzes the capability of the framework to implement catalytic circuits analogous to phosphorylation networks in living cells.

Quasi-robust control of biochemical reaction networks via stochastic morphing

The stochastic morpher controller is put forward that can, under suitable timescale separations, morph the probability distribution of the target molecular species into a predefined form, allowing one to achieve desired multi-modality/multi-stability and arbitrary probability distributions.

Life efficiency does not always increase with the dissipation rate

This work uses examples of molecular motors, of circadian cycles and of sensory adaptation, whose performance in some regimes is indeed spoiled by increasing the dissipated power, to make claims about the relation between dissipation and the amount of time-reversal breaking.

26th International Conference on DNA Computing and Molecular Programming, DNA 26, September 14-17, 2020, Oxford, UK (Virtual Conference)

It is proved that if a graph admits an embedding in a torus that is not checkerboard colorable, then it can be re-embedded so that all its non-intersecting Eulerian circuits are knotted.



Modular cell biology: retroactivity and insulation

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.

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

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

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

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

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.

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.