Team:Imperial College London/Modelling/Protein Display/Results and Conclusion

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Modelling Overview | Detection Model | Signaling Model | Fast Response Model | Interactions
A major part of the project consisted of modelling each module. This enabled us to decide which ideas we should implement. Look at the Fast Response page for a great example of how modelling has made a major impact on our design!
Objectives | Description | Results | Constants | MATLAB Code
Results and Conclusion
The graph below presents standard output of our model. It shows how concentration of each of the species varies with time.
IC Protein display.png
Graphs showing the simulation using [TEV]0 = 400 nM. The graph on the right hand-side
bottom shows that the AIP threshold (red line) is reached after 11 s!


Sensitivity of our model

  • Changing initial concentration of TEV
    • Whether the threshold concentration of AIP is reached is highly dependent on the initial concentration of TEV. On the graph below it can be seen that the optimal [TEV]0 is a concentration higher than 10nM, which corresponds to the threshold being reached within 9 minutes.

    IC AIP threshold.png
    Graph showing when threshold AIP concentration is reached
    (for different initial TEV concentrations). Notice log-log scale.


  • Changing the production rate
    • One order of magnitude change in the production rate results in at least 50s delay of the AIP concentration reaching the threshold concentration.


Risk of False positives
It was pointed out that we should assess the risk of false positive activation of the receptor, but only areas of research were determined. We are particularly concerned about the display protein not binding to the cell wall, but instead diffusing into the extra-cellular environment and maybe attaching to receptor. In order to be able to assess the risk of false positives, we need to do further research into the affinity of AIP with attached linker and trans-membrane proteins for the receptor as compared to the affinity of the AIP itself for the receptor.
This paper [1] might have some information on affinity comparison. We need to know how proteins are being transported from intracellular to trans-membrane space. Understanding of this concept could give us an idea of what could go wrong and on what modelling would need to focus on.

References

  1. Knutsen, E., Ween, O. & Havarstein, L. (2003) Two Separate Quorum-Sensing Systems Upregulate Transcription of the Same ABC Transporter in Streptococcus pneumoniae. Journal of Bacteriology. [Online] 186(10), 3078-3085. Available from: http://jb.asm.org/cgi/reprint/186/10/3078 [Accessed 1st September 2010]

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