NOT Gate

Intro

NOT Gate is a genetic logic circuit, presented by Hasan Baig and Jan Madsen in [Baig2017].

The NOT Gate genetic circuit represents a gene regulatory network that is triggered by a combination of external input signals. More specifically, when TetR input protein is present in significant amounts within the cell, it inhibits promoter P2 to activate and subsequently to produce the output protein GFP (green fluorescent protein).

IBL Modelling

Outlined below is the resulted IBL representation, after importing the corresponding SBML model into IBW. The NOT Gate IBL file can be downloaded here.

     define Cell typeof CELL() {

             // Species
             Promoter_GFP = MOLECULE(concentration=2.0 molecules)
             TetR = MOLECULE(concentration=0.0 molecules)
             GFP = MOLECULE(concentration=0.0 molecules)

             // Rules
             RULE Degradation_GFP : GFP ->
             Degradation_GFP.forwardRate = '0.0075*[GFP]'

             RULE R_abstracted_production_Promoter_GFP :  -> GFP + GFP + GFP + GFP + GFP + GFP + GFP + GFP + GFP + GFP
             R_abstracted_production_Promoter_GFP.forwardRate = '0.05*2.0*0.033*30.0/((1+0.033*30.0)+(0.5*[TetR])^2.0)'

             EVENT [TetR = 10 molecules] WHEN [TIME >= 1900 s]
     }

     define not typeof REGION () {
             CELL Cell = new Cell()
     }

Simulation

In order to analyse the trends in the concentration of the various molecular species, stochastic simulation has been performed, using the following parameters:

• Max Time: 3,400 seconds;
• Interval: 10 seconds;
• Number of runs: 10;

As depicted in the screenshot below, the result of the stochastic simulation shows that, after TetR input is triggered to 10 molecules (the high threshold), the nunmber of GFP protein molecules drops below the 10 molecules (high) threshold, with respect to a propagation delay of approximately 350 seconds. This result confirms the behaviour of the NOT gate.