In Practical 2, we have explored how gene expression can be controlled (positively or negatively) by other proteins. Here, we start to assemble genetic circuit by connecting genes. The model studied here is a simple genetic cascade, where a Gene_1 produces a protein which repressed the expression of Gene_2. Additionally, you are able to induce the expression of Gene_1 thanks to an inducer.
To start, launch the CellDesigner Application: Double Click on the Icon found on your Desktop.
Then follow the instructions below to build the model.
Define the topology of the reaction network:
Open a NEW document: File -> New.
Following the Law of Mass action, the dynamic of the system is described as:
Using the default kinetics parameters, build the following 3 transfer functions:
first, between the [inducer] concentration, and the Protein_1 steady-state expression level. Take the inducer level to vary between [0, 10000]. Comment on the behaviour observed (Illustrations)
second, between the Protein_1 concentration (to be kept constant during the simulations), and the Protein_2 steady-state expression level. Make sure that the range covered by the concentration of Protein_1 helps to explore the full dynamic range of system behaviour.
third, between the [inducer] concentration, and the Protein_2 steady-state expression level. Take the inducer level to vary between [0, 10000]. Comment on the behaviour observed (Illustrations)
We want to tune this cascade so that when using our maximal [inducer] concentration we are able to completely shut-down the expression of Protein_2. Suggest 2 independent strategies to achieve that result.
Suggest a strategy to characterise this model (Establish clear simulation scenarii to illustrate the properties of this genetic circuit. Tip: The cell designer function related to 'Change Amount' might be handy)
From your characterisation, how would you call this device ?
Imagine an application where this genetic device would be useful.