Team:Grenoble/Modeling/Amplification

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iGEM Grenoble 2012

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Introduction


In this part we will model the amplification module. Our work in this module is subdivided in three main parts: A deterministic model of the reactions at the local scale, another version of the former taking into account some random noise/perturbations, and a model of the signal's diffusion in space.

In the deterministic model, we checked the sensitivity of our system, in the diffusion part we checked if our system had a fast answer. Eventually in the random perturbations model, we checked that it was robust to perturbations.

Overview


We wanted to create a detector, thus we could have designed it like following:





Where X is the molecule to detect, and Z the fluorescent signal. However, with this design, the communication between the bacteria (quorum sensing) wouldn’t have worked really well, we would have needed an important quantity of X at the initial time to be able to obtain an important diffusion that we could actually see. Indeed, the evolution of X would have been like following:



Thus, the next idea was to amplify X:



Like this, as soon as it would be detected, by a bacterium, the bacterium would re-create some X, and the quorum sensing would work, as we would have this evolution of X:



Thanks to the quorum sensing if we detect X, we can easily measure it.

Now, we had a last problem: the false positives. Indeed, we have a detector, so we don’t want to have a signal if there is nothing to detect. Thus, we decided to add a classic feed forward loop, because it is known to reduce the false positives. Finally, we got our system:



X is a molecule that has the ability to be transmitted from bacterium to an other. It is a quorum-sensing molecule. Y, and Z are 2 genes. X is the transcription factor of Y. Thus when it is introduced, the gene Y is expressed. Then, the molecule X and the protein Y together will be the transcription factor of Z. When Z is expressed it creates more X.

Conclusion:

Now that we designed our system, we wanted to really study the behavior of this topology before going further in this project.