Models of microbial cell cycles

Abstract

Cell division is a fundamental process of life, yet how the timing of cell division is regulated in microorganisms remain unclear. In this dissertation, I use mathematical models to investigate the problem at the single-cell and molecular, as well as the phenomenological and mechanistic levels. First, I show how stochastic models similar to those used to describe random walks can describe the timing of divisions for diverse microbes. Together with analysis of single-cell data, the models showed that microbes in all three domains of life follow the same regulation strategy, despite drastic differences in their cell cycles. In particular, I show how different modes of coupling between DNA replication and cell division can coordinate the two processes when they occur in parallel to generate the same strategy for timing divisions in different microbes. I then proceed to the molecular level, and provide a progress report on the construction of a biophysical model for the mechanism underlying the regulation of the initiation of DNA replication in bacteria. Finally, I conclude by proposing a mechanistic model for how the circadian clock affects division timing in cyanobacteria. As a whole, the dissertation provides a step towards a quantitative and multi-scale understanding of microbial cell cycles.