Create Huygens pendulum clocks in bacteria using engineered gene network and microfluidic devices

Synthetic biology is a fascinating field! One example is described in the following paper.

Nature. 2010 Jan 21;463(7279):326-30.
A synchronized quorum of genetic clocks.
Danino T, Mondragón-Palomino O, Tsimring L, Hasty J.

Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.

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.

PMID: 20090747

This clock – synchronized oscillator – design is based the quorum sensing machineries. “We placed the luxI (from V. fischeri), aiiA (from B. Thurigensis) and yemGFP genes under the control of three identical copies of the luxI promoter. The LuxI synthase enzymatically produces an acyl-homoserine lactone (AHL), which is a small molecule that can diffuse across the cell membrane and mediates intercellular coupling. It binds intracellularly to the constitutively produced LuxR, and the LuxR–AHL complex is a transcriptional activator for the luxI pro-moter 36. AiiA negatively regulates the promoter by catalysing the degradation of AHL 37.”

To maintain the critical cell density required by the quorum sensing systems, the authors elegantly used microfluidic devices, which has rectangular trapping chambers and uses various flow to adjust cell density and supply nutrient for long term experiments. By tuning the flow rates, the authors could either increase or deceases the environment AHL concentration which affects the luxI promoter activity and the output of this genetic oscillator.

With slow flow rate, the authors observed the waving propagation pattern of this oscillator inside the microfluidic chambers, which can be modeled with spatiotemporal precision!

“We have shown how quorum sensing can be used to couple genetic clocks, leading to synchronized oscillations at the colony level. Given the single-cell variability and intrinsic stochasticity of most synthetic gene networks 27,30,31,45,46, the use of quorum sensing is a promising approach to increasing the sensitivity and robustness of the dynamic response to external signals.”