Abstract

Gene expression can be surprisingly dynamic and heterogeneous. This variability in gene expression, even in a clonal population of cells grown under the same condition, has been observed in diverse organisms, from mammalian stem cells to bacteria. It remains unclear how this variability is generated and what function it can serve.

We are using the B. subtilis general stress response regulator sigB as a model system to understand how heterogeneous cell states can be generated. By carrying out time-lapse microscopy of cells expressing a reporter of sigB activity, we discovered that sigB expression occurs in discrete pulses. The regulation of these pulses is input dependent. Energy stress causes sigB to be activated in continuous stochastic pulses. Environmental stress, however, results in a single pulse of sigB activation. By using a combination of mathematical modelling and synthetic biology techniques we were able to understand the mechanism of these two different dynamical regulation schemes. We are now testing the function and generality of pulsing as a regulatory strategy for the cell.