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Design principles for robust oscillatory behavior

  • Research Article
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Systems and Synthetic Biology

Abstract

Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions. We then identify network motifs, whose presence in more complex topologies is a necessary condition for obtaining oscillatory responses. Finally, we pinpoint a series of simple architectural patterns that progressively render more robust oscillators. Together, these findings can help in the design of more reliable synthetic biomolecular networks and may also have implications in the understanding of other oscillatory systems.

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Acknowledgments

The authors gratefully acknowledge the generous funding and support of Instituto de Investigación de Facultad de Ingeniería Mecánica (INIFIM), Instituto General de Investigación (IGI), Centro de Tecnologías de Información y Comunicaciones (CTIC), all part of Universidad Nacional de Ingeniería (UNI), Lima, Perú.

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Authors and Affiliations

  1. Faculty of Mechanical Engineering, Universidad Nacional de Ingeniería, Av. Túpac Amaru s/n - Puerta 3, Pabellón A, 25, Lima, Peru

    Sebastian M. Castillo-Hair, Elizabeth R. Villota & Alberto M. Coronado

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  1. Sebastian M. Castillo-Hair
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  2. Elizabeth R. Villota
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  3. Alberto M. Coronado
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Correspondence to Elizabeth R. Villota.

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Castillo-Hair, S.M., Villota, E.R. & Coronado, A.M. Design principles for robust oscillatory behavior. Syst Synth Biol 9, 125–133 (2015). https://doi.org/10.1007/s11693-015-9178-6

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  • DOI: https://doi.org/10.1007/s11693-015-9178-6

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