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

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  |<html>Graphs showing the simulation using [TEV]<sub>0</sub> = 4x10<sup>-4</sup> mol/dm<sup>3</sup>. The graph on the right hand-side<br/> bottom shows that the AIP threshold (red line) is reached after 22 s.</html>
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  |<html>Graphs showing the simulation using [TEV]<sub>0</sub> = 4&times;10<sup>-4</sup> mol/dm<sup>3</sup>. The graph on the right hand-side<br/> bottom shows that the AIP threshold (red line) is reached after 22 s.</html>
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<li>Changing initial concentration of TEV</li>
<li>Changing initial concentration of TEV</li>
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Whether the threshold concentration of AIP is reached is highly dependent on the initial concentration of TEV. The smallest initial concentration of TEV, [TEV>]<sub0</sub>, for which the threshold is reached is 6.0x10<sup>-6</sup>mol/dm<sup>3</sup>. On the grap below it can be seen that the optimal [TEV]<sub>0</sub> is a concentration higher than 10<sup>-4</sup>mol/dm<sup>3</sup>, which corresponds to the threshold being reached within 1.5 minutes.
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Whether the threshold concentration of AIP is reached is highly dependent on the initial concentration of TEV. The smallest initial concentration of TEV, [TEV>]<sub0</sub>, for which the threshold is reached is 6.0&times;10<sup>-6</sup>mol/dm<sup>3</sup>. On the grap below it can be seen that the optimal [TEV]<sub>0</sub> is a concentration higher than 10<sup>-4</sup>mol/dm<sup>3</sup>, which corresponds to the threshold being reached within 1.5 minutes.
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Revision as of 12:23, 22 October 2010

Temporary sub-menu:

Objectives; Detailed Description; Parameters & Constants; Results & Conclusion;Download MatLab Files;

Surface Protein Model
IC Protein display.png
Graphs showing the simulation using [TEV]0 = 4×10-4 mol/dm3. The graph on the right hand-side
bottom shows that the AIP threshold (red line) is reached after 22 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. The smallest initial concentration of TEV, [TEV>], for which the threshold is reached is 6.0×10-6mol/dm3. On the grap below it can be seen that the optimal [TEV]0 is a concentration higher than 10-4mol/dm3, which corresponds to the threshold being reached within 1.5 minutes.

    IC AIP Threshold concentration.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.

  • Changing production rate
    • Changing the production rate influences the time duration of the AIP concentration above the threshold level. The higher it is, the shorter the receptor will be activated (at extreme values, AIP concentration does not reach the threshold). However, the production rate has not much influence on how fast the threshold will be reached.

  • Changing control volume
    • Our model is extremely sensitive to this factor. One order of magnitude change in CV results in several orders of magnitude change in AIP concentration. Hence, special care should be taken in determination of this value. If the model is to be compared with the experimental results, the CFU/ml has to be the same as the one used in the model. Otherwise, the CV has to be readjusted.

Risk of False positives
It was pointed out that we should assess the risk of false positive activation of the receptor. We are particularly concerned about the display protein not binding to the cell wall, but instead diffusing into the extra-cellular environment. 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 transmembrane 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 transmembrane space. Understanding this concept could give us an idea of what could go wrong.

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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