2010 January 21 | Tal Danino, Octavio Mondragón-Palomino, Lev Tsimring, and Jeff Hasty
A synchronized genetic clock is described in a study published in Nature (2010). The research focuses on engineered gene networks that generate synchronized oscillations in a growing population of cells. The study uses microfluidic devices to investigate collective synchronization properties and spatiotemporal waves on millimeter scales. Computational modeling is used to describe the dependence of the period and amplitude of the bulk oscillations on the flow rate. The synchronized genetic clock has potential applications in creating macroscopic biosensors with oscillatory outputs and provides a model system for understanding emergent coordinated behavior at the colony level.
Synchronized clocks are important for coordinating rhythmic behavior among individual elements in a community or complex system. In physics and engineering, the Huygens paradigm of coupled pendulum clocks has influenced various fields, including the development of arrays of lasers and GPS. In biology, synchronized oscillators govern fundamental physiological processes such as somitogenesis, cardiac function, respiration, insulin secretion, and circadian rhythms. Synchronization helps stabilize desired behaviors arising from networks of intrinsically noisy and unreliable elements.
The study describes a synchronized oscillator design based on elements of quorum sensing mechanisms in Vibrio fisheri and Bacillus thuringiensis. The luxI promoter drives the production of luxI, aiiA, and yemGFP genes in three identical transcriptional modules. LuxI produces an acyl-homoserine lactone (AHL), which diffuses across the cell membrane and mediates intercellular coupling. AiiA negatively regulates the circuit by degrading AHL. This network architecture is similar to motifs used in other synthetic oscillator designs and forms the core regulatory module for many circadian clock networks.
The study uses microfluidic devices to monitor the bulk oscillations and investigate spatiotemporal dynamics. The TDQS1 cells exhibit stable synchronized oscillations after an initial transient period. The dynamics of the oscillations are influenced by the flow rate, with higher flow rates leading to longer periods and lower amplitudes. The study also observes spatial propagation of the fluorescence signal across the chamber and spatiotemporal dynamics in a three-dimensional colony.
The study develops a computational model using delayed differential equations to describe the mechanisms driving bulk synchronization and wave propagation. The model includes the coupling of individual oscillators through extracellular AHL and shows how the velocity of the front propagation depends on the external AHL diffusion coefficient. The study also investigates how cell density plays a role in wave propagation and how oscillations are suppressed by high cell density in the middle of the colony.
The study shows that synchronized oscillations represent an emergent property of the colony that can be mechanistically explained in terms of the circuit design. Oscillations arise because the small molecule AHL plays a dual role, both enabling activation of the genes necessary for intracellular oscillations and mediating the coupling between cells. The study also shows that individual cells oscillate independently when decoupled from the environment and each other.
TheA synchronized genetic clock is described in a study published in Nature (2010). The research focuses on engineered gene networks that generate synchronized oscillations in a growing population of cells. The study uses microfluidic devices to investigate collective synchronization properties and spatiotemporal waves on millimeter scales. Computational modeling is used to describe the dependence of the period and amplitude of the bulk oscillations on the flow rate. The synchronized genetic clock has potential applications in creating macroscopic biosensors with oscillatory outputs and provides a model system for understanding emergent coordinated behavior at the colony level.
Synchronized clocks are important for coordinating rhythmic behavior among individual elements in a community or complex system. In physics and engineering, the Huygens paradigm of coupled pendulum clocks has influenced various fields, including the development of arrays of lasers and GPS. In biology, synchronized oscillators govern fundamental physiological processes such as somitogenesis, cardiac function, respiration, insulin secretion, and circadian rhythms. Synchronization helps stabilize desired behaviors arising from networks of intrinsically noisy and unreliable elements.
The study describes a synchronized oscillator design based on elements of quorum sensing mechanisms in Vibrio fisheri and Bacillus thuringiensis. The luxI promoter drives the production of luxI, aiiA, and yemGFP genes in three identical transcriptional modules. LuxI produces an acyl-homoserine lactone (AHL), which diffuses across the cell membrane and mediates intercellular coupling. AiiA negatively regulates the circuit by degrading AHL. This network architecture is similar to motifs used in other synthetic oscillator designs and forms the core regulatory module for many circadian clock networks.
The study uses microfluidic devices to monitor the bulk oscillations and investigate spatiotemporal dynamics. The TDQS1 cells exhibit stable synchronized oscillations after an initial transient period. The dynamics of the oscillations are influenced by the flow rate, with higher flow rates leading to longer periods and lower amplitudes. The study also observes spatial propagation of the fluorescence signal across the chamber and spatiotemporal dynamics in a three-dimensional colony.
The study develops a computational model using delayed differential equations to describe the mechanisms driving bulk synchronization and wave propagation. The model includes the coupling of individual oscillators through extracellular AHL and shows how the velocity of the front propagation depends on the external AHL diffusion coefficient. The study also investigates how cell density plays a role in wave propagation and how oscillations are suppressed by high cell density in the middle of the colony.
The study shows that synchronized oscillations represent an emergent property of the colony that can be mechanistically explained in terms of the circuit design. Oscillations arise because the small molecule AHL plays a dual role, both enabling activation of the genes necessary for intracellular oscillations and mediating the coupling between cells. The study also shows that individual cells oscillate independently when decoupled from the environment and each other.
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