Team:TU-Delft/Modeling/SingleCellModel

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Team:TUDelft/CSSLaksh Menu

Human Outreach


The single-cell pathway model of our system is composed of 4 modules, which are responsible for routing the signal from the receptor to the GFP sythesis. The mathematical models were developed on a scheme favoring the temporal order of processes, based on the current understanding of the pheromone signalling pathway from [1][2][3] and also on the feedback received from the experimentalists on the expected behaviour of the pathway, taking into consideration the aspects relevant to our project.

Assumptions

In all of the models developed certain assumptions were made due to the lack of data available on the new modified pathway and also due to the time constraints which limit the range of experiments that can be carried out. The assumptions made are listed below.

  • The rate constants and initial concentrations obtained from the literature are assumed to be the same for the new modified pathway.
  • The behaviour of the Ligand is assumed to be similar to the behaviour of the alpha pheromone.
  • The tuberculosis receptor is assumed to behave similar to the alpha-pheromone receptor.

Model of the G - Protein cycle

The concentration of free G-beta-gamma dimer is crucial for the activation of the MAP kinase cascade which in turn activates the
Figure 1: Reaction diagram of heterotrimeric G protein cycle[1]. The individual reactions comprising the key dynamics of heterotrimeric G proteins in yeast are represented along with the rate constants
expression of the GFP. The promoter used for the receptor and the initial concentration of the ligand were thus crucial parameters for the activation of the G-Protein Cycle. A model of the G-Protein cycle by Yi et al [1] was used to analyze the effects of the different promoter strengths of the receptor.

It can be seen that as the concentration of G-alpha-GDP increases the concentration of free G-beta-gamma dimer reduces, which motivates the use of a promoter which is weak or medium strength compared to a strong promoter.

File:PromoterStrengthAnalysis.gif
Figure 2: Effect of varying the strength of the promoter.



References

Source
[1] Tau-Mu Yi, Hiroaki Kitano, and Melvin I. Simon,
A quantitative characterization of the yeast heterotrimeric G protein cycle,
PNAS September 16, 2003 vol. 100 no. 19
[2] Kofahl B, Klipp E,
Modelling the dynamics of the yeast pheromone pathway,
Yeast 2004; 21: 831–850



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