Abstract

BackgroundThe ultimate goal of synthetic biology is the conception and construction of genetic circuits that are reliable with respect to their designed function (e.g. oscillators, switches). This task remains still to be attained due to the inherent synergy of the biological building blocks and to an insufficient feedback between experiments and mathematical models. Nevertheless, the progress in these directions has been substantial.ResultsIt has been emphasized in the literature that the architecture of a genetic oscillator must include positive (activating) and negative (inhibiting) genetic interactions in order to yield robust oscillations. Our results point out that the oscillatory capacity is not only affected by the interaction polarity but by how it is implemented at promoter level. For a chosen oscillator architecture, we show by means of numerical simulations that the existence or lack of competition between activator and inhibitor at promoter level affects the probability of producing oscillations and also leaves characteristic fingerprints on the associated period/amplitude features.ConclusionsIn comparison with non-competitive binding at promoters, competition drastically reduces the region of the parameters space characterized by oscillatory solutions. Moreover, while competition leads to pulse-like oscillations with long-tail distribution in period and amplitude for various parameters or noisy conditions, the non-competitive scenario shows a characteristic frequency and confined amplitude values. Our study also situates the competition mechanism in the context of existing genetic oscillators, with emphasis on the Atkinson oscillator.

Highlights

  • Introduction to Nonlinear Science Cambridge UniversityPress; 1995.67

  • In the relatively young field of synthetic biology [1,2], there is increasing interest in the conception and construction of genetic circuits that are reliable with respect to their designed function

  • On two-component genetic oscillators To achieve the goal of reliable synthetic circuits, several strategies have been employed by the community

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Summary

Introduction

Introduction to Nonlinear Science Cambridge UniversityPress; 1995.67. Izhikevich EMDynamical Systems in Neuroscience. The ultimate goal of synthetic biology is the conception and construction of genetic circuits that are reliable with respect to their designed function (e.g. oscillators, switches). This task remains still to be attained due to the inherent synergy of the biological building blocks and to an insufficient feedback between experiments and mathematical models. In the relatively young field of synthetic biology [1,2], there is increasing interest in the conception and construction of genetic circuits that are reliable with respect to their designed function. Having given the first step with the implementation of biological switches [3], the step for synthetic biology was the construction of biological oscillators. Intuition alone cannot grasp the effects of multiple regulatory interactions and mathematical models are well suited for unraveling the implications of the underlying nonlinear interactions [10,11,12,13,14]

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