A synchronized quorum of genetic clocks

By Tal Danino, O. Mondragón-Palomino, Lev S. Tsimring, Jeff Hasty. Nature, 2010

1,019 citations recorded by the source corpus.

The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic biology. This focus was elegantly set in motion a decade ago with the design and construction of a genetic toggle switch and an oscillator, with subsequent highlights that have included circuits capable of pattern generation, noise shaping, edge detection and event counting. Here we describe an engineered gene network with global intercellular coupling that is capable of generating synchronized oscillations in a growing population of cells. Using microfluidic devices tailored for cellular populations at differing length scales, we investigate the collective synchronization properties along with spatiotemporal waves occurring at millimetre scales. We use computational modelling to describe quantitatively the observed dependence of the period and amplitude of the bulk oscillations on the flow rate. The synchronized genetic clock sets the stage for the use of microbes in the creation of a macroscopic biosensor with an oscillatory output. Furthermore, it provides a specific model system for the generation of a mechanistic description of emergent coordinated behaviour at the colony level.

Subfields: Biomedical Engineering, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/7dc793e01d9bd0dbc5d7c15c694b8bc2f1a4db15

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Citations in the corpus

Oscillation quenching mechanisms: Amplitude vs. oscillation death (2013, background): “Therefore, several theoretical [70,71,43,72,59] and experimental models [68,73,74] of distinct synthetic oscillators or populations have been investigated in the literature.”
Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’ (2010, background): “As layered computation becomes more critical to the design of genetic programs, this will either require the implementation of a genetic clock 27 or the design of programs that are robust to asynchronous computation 28 .”
Synchronized cycles of bacterial lysis for in vivo delivery (2016, methodology): “In order to control population levels and facilitate drug delivery using bacteria, we engineered a synchronized lysis circuit (SLC) using coupled positive and negative feedback loops that have previously been used to generate robust oscillatory dynamics 12,13 .”
Nonequilibrium physics in biology (2019, methodology): “coli to generate synchronous population oscillations (Danino et al., 2010).”