Modeling cellular regulation by pulsatile inputs

Cellular regulation, at the level of both signalling and gene expression, is frequently mediated by proteins whose activity changes over time, often in a pulsatile manner. Here we discuss how mathematical modelling is helping our understanding of how cells respond to changes in the characteristics of pulsing signals, namely their amplitude, frequency, and duration. We review recent work combining theory and experiments that show how cellular output can be modulated by tuning the dynamical features of input pulses. This results in different outcomes depending on the circuit architecture connecting the input sensor with the output layer, and on the corresponding kinetic parameters. Given the ubiquitous presence of pulsatile activity in many cellular signals, studies such as the ones reviewed here are bound to cast new light on the mechanisms underlying cellular regulation.