Stochastic induction dynamics of the lac operon*

Gene regulation is paramount to bacterial survival in changing environment. Important aspects of gene regulation have been discovered through bulk experiments and allowed the development of predictive models. However, two aspects of gene regulation remain challenging to observe experimentally without well controlled growth conditions and single cell information: (i) the mechanism driving the stochastic triggering of rare molecular events and (ii) the dynamics of gene regulation in response to environmental fluctuations.

The Lac operon can be conveniently exploited to measure rare events. Indeed, the feedback loop is enabling experimental measurement in two ways: (i) the gene expression can be gradually tuned down using inducer molecule and (ii) rare gene expression event can be easily observed as they will trigger a feedback loop and irreversibly turn it ON [Novick & Wiener 1957].

By using microfluidic devices coupled with fluorescence microscopy we dynamically monitor the state of the feedback loop in controlled growth conditions. We can measure both the time required to initiate and the dynamics of the feedback loop activation process. We observe that the feedback loop activation is stochastic, and days can separate the activation of cells growing in separated chamber when gene expression is tuned down. This finding supports the idea that rare event triggering phenotypic change can be solely due to stochastic expression of a strongly repressed gene.