Team:Wageningen UR/menutest

Quorum sensing and cell lysis

We developed a mathematical model of the quorum sensing and cell lysis system. The goals of the mathematical model are the following. To characterize the theoretical properties of the system. To identify which kinetic parameters dictate the behavior of the system. To determine which parameter, that can be changed in the lab, can be varied to obtain a system with the correct behavior. To achieve this goal, the Simple model was first developed. The Simple model was used to sample the global parameter space. The second model that we used is the Spatial Model. This model was used to test hypothesis and to guide wet-lab experiments.
With the modeling of the quorum sensing and cell lysis system we had the following goals.

  • Characterize system behavior
  • Sample global parameter space
  • Identify parameters with high sensitivity
  • Find lab-tunable parameters
  • Test hypothesis

Summary

We developed a mathematical model of our quorum sensing & cell lysis module. In this model, both LuxR and LuxI are positively regulated by the [AHL-LuxR] dimer. Our model predicts that by changing the degradation rate of LuxR, a bad parameter set may be recovered into a good parameter set. In case of spontaneos auto-activation, the degradation rate of LuxR should be increased. For a system unresponsive to the AHL-signaling by antigen-activated cells, the degradation of LuxR should be decreased.

For the system to function properly, it needs the following behaviors.

Bistability:
Cells must be able to switch from an OFF-state to an ON-state. This requires that the system of ODE equations has equilibrium state solutions.
Cell signaling:
Cells in the ON-state should be able to signal cells in the OFF-state to also transition to the ON-state.
Delayed cell lysis:
Cells in the ON-state should lyse to release their split fluorescent protein. But they should do so only after singaling cells still in the OFF-state.