Nonlinear response s to signals are widespread natural phenomen a that affect vari ous cellular processes. Nonlinearity can be a desirable characteristic for engineering living organisms because it can lead to more switch - like responses, similar to those underlying the wiring in electronics. Steeper functions are described as ultrasensit ive , and can be applied in synthetic biology by using various techniques including receptor decoys, multiple co - operative binding sites, and sequential positive feedbacks . Here, we explore the inherent non - linearity of a biological signaling system to iden tify functions that can potentially be exploited using cell genome engineering . For this, we performed genome - wide transcription profiling to identify genes with ultrasensitive response function s to Hepatocyte Growth Factor (HGF) . We identified 3, 527 genes that react to increasing concentrations of HGF , in Madin - Darby canine kidney (MDCK) cells , grown as cysts in 3D collagen cell culture . By fitting a generic Hill function to the dose - response s of these genes we obtained a measure of the ultrasensitivity of HGF - responsive genes , identifying a subset with higher apparent Hill coefficients (e.g. MMP1, TIMP1 , SNORD75, SNORD86 and ERRFI1 ). The regulatory regions of these genes are potential candidates for future engineering of synthetic mammalian gene ci rcuits r equiring non linear responses to HGF signalling.