Team:TU Delft-Leiden/Modeling/Landmine

Landmine Module

An important part of our iGEM project is a promoter sensitive to landmines, first described by Yagur-Kroll et al. [1]. We will use two of the promoters described in this paper, ybiJ and ybiFB2A1, in our project. Of these promoters, not much is known other than the fact that they have a DNT/TNT-dependent response curve (see figure 1). Our goal was to find a model which would be able to reproduce the response curves of both promoters.

Our first approach was to solve a system of Ordinary Differential Equations (ODEs) resembling the transcription and translation of a gene activated by the DNT-sensitive promoter. The ODEs were derived from the following system of reactions: $$ P_{R} + DNT \ \overset{k_{on}}{\underset{k_{off}}{\rightleftharpoons}} \ P_{A} \tag{1} $$ $$ P_{A} \ \xrightarrow{s_{A}} \ P_{A} + mRNA \tag{2} $$ $$ P_{R} \ \xrightarrow{s_{R}} \ P_{R} + mRNA \tag{3} $$ $$ mRNA \ \xrightarrow{s_{P}} \ mRNA + R \tag{4} $$ $$ mRNA \ \xrightarrow{d_{M}} \ \emptyset \tag{5} $$ $$ R\ \xrightarrow{d_{P}} \ \emptyset \tag{6} $$ In these reaction equations, \(P_{R}\) and \(P_{A}\) indicate respectively repressed and active promoters. DNT indicates DNT molecules, mRNA stands for an mRNA molecule transcribed from the gene behind the promoter and R is the reporter protein which is translated from the mRNA. \(k_{on}\) and \(k_{off}\) are the rates at which a promoter goes from the repressed to the active state and vice versa. \(s_{A}\) is the transcription rate from an active promoter. \(s_{R}\) is the transcription rate from a repressed promoter; this is also referred to as leakage. \(s_{P}\) is the translation rate. \(d_{M}\) and \(d_{P}\) are the mRNA and protein degradation rates.