Getting Gardner2000's toggle switch to toggle

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Sara Kalvala

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Feb 14, 2023, 8:05:19 AM2/14/23
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Hi all - the genetic toggle switch is frequently used as an example of why stochastic simulation is important, see for example the excellent tutorial at https://www.math.uwaterloo.ca/~mscott/NoiseTutorial.pdf

I was hoping I could demonstrate this behaviour using the Biomodel called Gardner2000, but try as much as I have I haven't been able to obtain a time series that gets U and V quantities to flip. 

Does anyone know how I can tweak the parameters to get the nice textbook toggling behaviour?

(Do you have another nice example of the marked effect of stochastic simulations?)

Thanks in advance! Sara

Frank Bergmann

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Feb 14, 2023, 8:55:38 AM2/14/23
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Hello Sarah, 

the first thing you could do, is what the biomodels team did as well, they ran a steady state scan over the IPTG concentration: 

image.png

the other thing would be to: 

* change the model units or compartment size (since there are way too many elements in the original model for stochastic simulations)
* set a time course to use a stochastic method
* add a plot and run a couple of times, and you will see the switch behavior. 

copasi files attached

I hope this helps, 

best
Frank


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Gardner_Stoch.cps
Gardner_Scan.cps

Sara Kalvala

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Feb 14, 2023, 11:21:47 AM2/14/23
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Many thanks Frank, that is very helpful. I did play with volume and species quantities which makes the time course a bit more understandable. I think what I need to do is add a production rule for IPTG and see if it causes a toggle in the time graph. I can see this will be my learning Copasi challenge...

Thanks, - Sara

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