Team:NTNU Trondheim/Yeast

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<h1>Collaboration with RHiT; Yeast modelling <small>Stochastic simulations of the genetic circuit</small></h1>
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<span class="heading">Collaboration with RHiT; Yeast modelling<hr/></span>
 
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Our part of the collaboration with RHiT was helping them with stochastic modelling of the trigger system for mating in yeast. The full mechanism has been quite well studied, but it is very complicated[http://dx.doi.org/10.1002/yea.1122]. In RHiTs [[Team:RHIT/Modeling|model]], the final steps of the mechanism is activation of the Ste12 protein by the Fus3 enzyme. To simplify the model, production of Fus3 in the model was described by a sigmoid curve found in experiments[http://dx.doi.org/10.1038/nature08946] with respect to the concentration of &alpha;-pheromone. Inactive Ste12 was quickly activated by the presence of Fus3, so the outcome of active Ste12 followed a similar sigmoid curve, giving the expected switch behaviour. The resulting plot is shown in Figure 1. Each point is the average of 100 trajectories with the error bars indicating one standard deviation.
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[[File:NTNU_Trondheim_YeastAlpha.png|thumb|450px|Figure 1. Amount of activated Ste12 at steady state as a response to &alpha;-pheromone concentrations. Error bars show one standard deviation.]]
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[[File:NTNU_Trondheim_YeastAlpha.png|thumb|center|450px|Figure 1. Amount of activated Ste12 at steady state as a response to &alpha;-pheromone concentrations. Error bars show one standard deviation.]]
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Our part of the collaboration with RHiT was helping them with stochastic modelling of the trigger system for mating in yeast. The full mechanism has been quite well studied, but it is very complicated[http://dx.doi.org/10.1002/yea.1122]. In RHiTs [[Team:RHIT/Modeling|model]], the final steps of the mechanism is activation of the Ste12 protein by the Fus3 enzyme. To simplify the model, production of Fus3 in the model was described by a sigmoid curve found in experiments[http://dx.doi.org/10.1038/nature08946] with respect to the concentration of &alpha;-pheromone. Inactive Ste12 was quickly activated by the presence of Fus3, so the outcome of active Ste12 followed a similar sigmoid curve, giving the expected switch behaviour. The resulting plot is shown in Figure 1. Each point is the average of 100 trajectories with the error bars indicating one standard deviation.
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The equations used in the model are given in the table below. The parameters are taken from[http://dx.doi.org/10.1002/yea.1122 [1<nowiki>]</nowiki>] and are modelled using mass action solvers, except Fus3 &rarr; Fus3PP, which use a sigmoid function. Timesteps in the model are minutes.
The equations used in the model are given in the table below. The parameters are taken from[http://dx.doi.org/10.1002/yea.1122 [1<nowiki>]</nowiki>] and are modelled using mass action solvers, except Fus3 &rarr; Fus3PP, which use a sigmoid function. Timesteps in the model are minutes.
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''* The function for Fus3 activation is given by'' 200*&alpha;⁶/(&alpha;⁶ + 150⁶) ''where &alpha; is the concentration of &alpha;-phermone in nM''
''* The function for Fus3 activation is given by'' 200*&alpha;⁶/(&alpha;⁶ + 150⁶) ''where &alpha; is the concentration of &alpha;-phermone in nM''
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The initial amounts are given in the table below.
The initial amounts are given in the table below.
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A .zip file of the full model can be downloaded [[Media:NTNU_Trondheim_Yeast.zip|here]].
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A .zip file of the model can be downloaded [[Media:NTNU_Trondheim_Yeast.zip|here]]. The original file is in .xml format and can be opened with the Cain software[http://cain.sourceforge.net].
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Latest revision as of 23:23, 26 September 2012

NTNU IS B.A.C.K.
Bacterial Anti-Cancer-Kamikaze

Collaboration with RHiT; Yeast modelling Stochastic simulations of the genetic circuit

Our part of the collaboration with RHiT was helping them with stochastic modelling of the trigger system for mating in yeast. The full mechanism has been quite well studied, but it is very complicated[1]. In RHiTs model, the final steps of the mechanism is activation of the Ste12 protein by the Fus3 enzyme. To simplify the model, production of Fus3 in the model was described by a sigmoid curve found in experiments[2] with respect to the concentration of α-pheromone. Inactive Ste12 was quickly activated by the presence of Fus3, so the outcome of active Ste12 followed a similar sigmoid curve, giving the expected switch behaviour. The resulting plot is shown in Figure 1. Each point is the average of 100 trajectories with the error bars indicating one standard deviation.

Figure 1. Amount of activated Ste12 at steady state as a response to α-pheromone concentrations. Error bars show one standard deviation.

The equations used in the model are given in the table below. The parameters are taken from[1] and are modelled using mass action solvers, except Fus3 → Fus3PP, which use a sigmoid function. Timesteps in the model are minutes.

Reaction Propensity Comment
Fus3 → Fus3PP * Activation of Fus3
Fus3PP → Fus3 150 Deactivation of Fus3
Fus3PP + Ste12 → Fus3Ste12 18 Activation of Ste12 through complexation with Fus3
Fus3Ste12 → Fus3PP + Ste12 10 Deactivation of Ste12 by release of Fus3
Bar1 + Fus3Ste12 → aBar1 + Fus3Ste12 0.1 Activation of Bar1 enzyme
aBar1 → Bar1 0.1 Deactivation of Bar1
aBar1 → ø 0.01 Export of active Bar1

* The function for Fus3 activation is given by 200*α⁶/(α⁶ + 150⁶) where α is the concentration of α-phermone in nM

The initial amounts are given in the table below.

Species Amount
Fus3 200
Fus3PP 0
Ste12 200
Fus3Ste12 0
Bar1 200
aBar1 0

A .zip file of the model can be downloaded here. The original file is in .xml format and can be opened with the Cain software[3].



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