Abstract
BackgroundA practical problem during the analysis of natural networks is their complexity, thus the use of synthetic circuits would allow to unveil the natural mechanisms of operation. Autocatalytic gene regulatory networks play an important role in shaping the development of multicellular organisms, whereas oscillatory circuits are used to control gene expression under variable environments such as the light-dark cycle.ResultsWe propose a new mechanism to generate developmental patterns and oscillations using a minimal number of genes. For this, we design a synthetic gene circuit with an antagonistic self-regulation to study the spatio-temporal control of protein expression. Here, we show that our minimal system can behave as a biological clock or memory, and it exhibites an inherent robustness due to a quorum sensing mechanism. We analyze this property by accounting for molecular noise in an heterogeneous population. We also show how the period of the oscillations is tunable by environmental signals, and we study the bifurcations of the system by constructing different phase diagrams.ConclusionsAs this minimal circuit is based on a single transcriptional unit, it provides a new mechanism based on post-translational interactions to generate targeted spatio-temporal behavior.
Highlights
A practical problem during the analysis of natural networks is their complexity, the use of synthetic circuits would allow to unveil the natural mechanisms of operation
The system, a single transcriptional unit, consists in a combinatorial promoter, lactose-luciferase, which controls the expression of two transcription factors (TFs) LacI and LuxR, and the enzyme LuxI
The models including the spatial dimension require the use of several genes with uncoupled dynamics
Summary
A practical problem during the analysis of natural networks is their complexity, the use of synthetic circuits would allow to unveil the natural mechanisms of operation. Synthetic Biology aims to engineer genetic networks with defined dynamics [1] It usually relies on the use of design principles derived from the analysis of natural genetic networks. Those networks are large and complex systems with many unknown interactions that can dramatically affect the system dynamics. For a complete understanding of the mechanisms underlying gene networks it is valuable the engineering of synthetic circuits that have a minimal complexity. Such small circuits would allow the modular design of complex hierarchical structures with targeted spatial and temporal behaviors. The extreme case being the design of a genetic network composed of a single transcriptional unit showing a specified spatio-temporal
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