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Network Design - Part 3


Synchronizing the oscillations at a population level

In order to make our system easier to observe, we need to extend and synchronize the oscillations at a population scale. The best way to do so is to insert a check-point that can be overcome only if the major part of the population has reached it. The phenomenon of quorum-sensing is the way bacteria synchronize the expression of genes when the density of bacteria is important enough.

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The Hawaiian bobtail squid have a symbiotic relationship with Vibrio fischeri

Presentation of the phenomenon of quorum-sensing : intercellular communication in bacterias

The phenomenon of quorum sensing was first discovered in Vibrio fischeri. This bacteria only expresses luciferase when the density of bacteria is very high (1011bact/mL). Typically, the bacteria does not express bioluminescence when they are free living in the ocean. At the contrary, they express luciferase when they are highly concentrated in the photophore of Hawaiian bobtail squid.

Fig 1 : Quorum sensing in V. fischeri. (Red triangle represent AHL produced by LuxI. OM : Outer Membrane, IM : Inner Membrane

The genetic cascade

In this system, LuxI and LuxR control the expression of luciferase operon luxICDABE, necessary to produce bioluminescence. LuxI synthesize small diffusible molecules called Acyl Homoserin Lactone (AHL). LuxR is the intracellular receptor to AHL.

The AHL freely diffuses into the extracellular medium. Its concentration increases as the population gets more dense. When the concentration reaches a critical level, those small molecules bind to their receptor. LuxR bound to AHL and the complex activate the operon that code for luciferase (Figure 1.).

Quorum Sensing and Synthetic biology

This system has already been used in the field of synthetic biology to create new behaviors. For instance, Lingchong YOU et al. (2004) designed a bacteria that regulates the maximum density of bacteria inducing a controlled suicide via intercellular communication. With this system, even if the population is stable the genome is expressed as if they were in exponential growth.

Fig 2 : Structure of two different AHL. In orange the common part to all AHL. A : 3OC6-HSL synthesized by LuxI. B : 3OC1-HSL synthesized by LasI

Other quorum sensing systems has been described in different species of baceteria such as Pseudomonas aeruginosa. The system has the same architecture with protein LasI that synthesize the AHL that binds to LasR, the intracellular receptor. One of the differences between those to systems is the structure of the AHL (Figure 2.)

The use of two quorum sensing system is possible. This is one of the challenges that Frederick K. BALAGADDE et al. (2008) carried out successfully. They constructed a synthetic ecosystem that imitates the prey-predator relationship in two different strains of E. coli.


The existence of this intercellular communication system causes another delay at the end of each cycle. According to our models, this delay creates good quality oscillations. The global system is represented on the following network.

Global genetic network