BioModel Engineering for Systems and Synthetic Biology
Lab 1

David Gilbert
Centre for Systems and Synthetic Biology
Brunel University, London, UK


Pratical exercises for Workshop on "BioModel Engineering for Systems and Synthetic Biology" at Modelling in systems biology and synthetic biology (10-21 June 2013)

Aim

The aim of this laboratory is to give you some familiarity with building Petri net models: qualitative, and quantitative (both continuous and stochastic), and to gain experience with constructing such models from basic components.

Exercises

  1. Ensure that you have installed Snoopy on your computer.

  2. Construct a qualitative Petri net model for an enzymatic reaction, of type MA1 (simple mass action), and explore the behaviour of this model using token game. Play with the relationship between the number of tokens for the substrate and for the enzyme.

  3. Extend your qualitative model to enzymatic reaction type MA2, and explore the behaviour.

  4. Extend your qualitative model to enzymatic reaction type MA3, and explore the behaviour.

  5. Can you use any of your simple enzymatic models to construct a model of a reaction with two substrates? I.e. A1 + A2 + E ---> B + E. Hint: You may need to expand the stages indicated by the `--->' arrow. If you base your model on MA1, then call it M2A1 (likewise M2A2 or M2A3 for MA2 and MA3 respectively).

  6. Convert your MA1 qualitative model into a continuous quantitative model. You will need to make some assumptions about the rates. Explore the behaviour of this model on Snoopy, using different ODE solvers. Play with the relationship between the concentrations for the substrate and for the enzyme.

  7. Convert your MA1 continuous model into a stochastic quantitative model. You will need to make some assumptions about the rates. Explore the behaviour of this model on Snoopy.

  8. Create continuous and stochastic versions of your MA2, MA3, and M2A[1,2,3] models, and explore their behaviours.

  9. Create a model for a template metabolic pathway. You can have any number of stages -- try 3 stages. You can create qualitative, continuous and stochastic versions.

  10. Create a model for an template 3-stage signal transduction pathway (no dephosphorylation). You can create qualitative, continuous and stochastic versions.

  11. Create a model for one phosphoylation-dephosphorylation stage in a signal transduction pathway.

  12. Use your phosphoylation-dephosphorylation stage as a building block to create a 3-stage phosphorylation-dephosphorylation signal transduction cascade.

  13. Add a negative feedback loop to your 3-stage phosphorylation-dephosphorylation signal transduction cascade. This will produce a negative feedback amplifier (NFA).

  14. Insert a drug inhibitor on the second stage of your 3-stage phosphorylation-dephosphorylation signal transduction cascade (optionally include the negative feedback loop from the pervious exercise).

  15. In theory you should be able to obtain oscillations from your negative feedback amplifier (why?). You could try to get it to oscillate by modifying the rate constants -- but this is hard and you will take a lot of time to explore the solution space!