Project Description

Background

The Type-I Incoherent Feed-Forward Loop and Fold-Change Detection

The type-I incoherent feedforward loop (I1-FFL) is a gene network in which protein X activates a gene Z while simultaneously activating the production of a repressor of gene Z, labeled Y.

For this year’s project, we are aiming to construct an I1-FFL that can detect fold-changes in the levels of protein X. In other words, the expression of Z would be reliant on the relative change in X as opposed to absolute values of X. For example, if X changes from an arbitrary concentration of 1 to an arbitrary concentration of 5, the level of expression of gene Z would be exactly the same as that resulting from a change from a concentration of 5 to a concentration of 25 of X (a fold-change by a factor of 5 in both cases).

How Fold-Change Detection is Achieved

This fold-change detection is enabled through the repressor Y. Take the case when activator X, repressor Y, and protein Z each have an arbitrary concentration of 1in the cell (1:1:1 ratio). If the concentration of X is doubled, the ratio between X and Y now becomes 2:1. X immediately activates Z, but since the repressor Y takes time to fold, it lags behind, and the concentration of Z spikes to 2 due to the activation. When Y folds into its active form and carries out its repressive activity, the concentration of Z returns to its initial concentration of 1. This is because at this point, X and Y return to a 1:1 ratio in the cell. In order for the concentration of Z to reach 2 once again, the X:Y ratio must first return to 2:1 - thus, X has to reach a concentration of 4 before the same output of Z is produced. In this way, fold-change detection is achieved.