TY - JOUR AB - Nonlinearresponses to signalsarewidespread natural phenomenathat affect various cellular processes. Nonlinearitycan bea desirable characteristic for engineering living organismsbecause it can lead to more switch-like responses, similar to those underlying the wiring inelectronics. Steeperfunctions are described as ultrasensitive, and can be applied in synthetic biologyby using various techniquesincludingreceptor decoys, multiple co-operative binding sites, and sequentialpositive feedbacks. Here, we explore the inherent non-linearity of a biological signaling system to identify functions that can potentially be exploited using cell genome engineering.For this,we performed genome-wide transcription profilingto identify genes with ultrasensitiveresponse functionsto Hepatocyte Growth Factor (HGF). Weidentified3,527genesthat react to increasing concentrations of HGF, in Madin-Darby canine kidney (MDCK) cells,grown as cystsin 3D collagen cell culture. By fitting a generic Hill function to the dose-responsesof these genes we obtained ameasure of the ultrasensitivityofHGF-responsive genes, identifying a subset with higher apparent Hill coefficients (e.g. MMP1, TIMP1,SNORD75, SNORD86 andERRFI1). The regulatory regions of these genes are potential candidates for future engineering of synthetic mammalian gene circuits requiring nonlinear responses to HGF signalling. AU - Senthivel,V AU - Sturrock,M AU - Piedrafita,G AU - Isalan,M DO - 10.1038/srep39178 PY - 2016/// SN - 2045-2322 TI - Identifying ultrasensitive HGF dose-response functions in a 3D mammalian system for synthetic morphogenesis T2 - Scientific Reports UR - http://dx.doi.org/10.1038/srep39178 UR - http://hdl.handle.net/10044/1/42705 VL - 6 ER -