Fig. 1: Alternative synthetic circuits for high-performance inducible gene expression.
From: Engineering a synthetic gene circuit for high-performance inducible expression in mammalian systems
a The dose response curve of an inducible gene expression system and its features. Leakiness: basal gene expression level in the absence of the inducer. Maximum expression: gene expression at saturating concentration of the inducer. Fold Induction: ratio between Maximum expression and Leakiness. b Schematics of the naïve configuration (NC) of an inducible gene expression system and of alternative circuits: CFFL-4, Coherent Feed Forward Loop 4; MI, Mutual Inhibition; CIL, Coherent Inhibitory Loop. Pointed arrows represent activation while blunt head arrows represent repression. The activity of species X can be modulated by an inducer molecule. c–e Numerical simulations of the level of species Z at different concentrations of the inducer molecules for the different circuits: CFFL-4 (blue), MI (red), and CIL (green) against the naïve TF (black). Simulated output values are shown either in a log-scale (top) to highlight differences in the absence of inducer molecule (leakiness), or as a linear-scale (middle) to highlight difference at the highest concentration of the inducer molecule (maximum expression), or as fold-induction values (bottom) computed as the ratio between each output value and its value in the absence of inducer molecule. f Numerical analysis of the Fold Induction (FI) in the three circuits for increasing levels of the inducer molecule (denoted as D) on the x-axis and for different numerical values of the parameter Kzy representing the repression strength of species Y over species Z. TF: Transcription-based inducible gene system; CFFL-4: Coherent Feed Forward Loop-4 circuit topology; MI: Mutually Inhibition circuit topology; CIL: Coherent Inhibitory Loop circuit topology.
