UC San Diego

Each cell must achieve the dual tasks of replicating the genetic material and dividing its components into its daughters. This thesis is concerned with how the cell coordinates those fundamental requirements. It approaches this question from the perspective of bacterial physiology, looking at the global relationship between these processes and growth at large. The thesis aims to uncover and test quantitative principles which govern this physiological orchestration. We first review the early quantitative principles, or growth laws, and their modern expansions. This includes cell size control, its connection with the cell cycle, and homeostatic control of each. We then explore these principles in the context of the model organisms E. coli and B. subtilis. Despite their evolutionary distance, we find the two species to be fundamentally similar in their physiological control. Finally, we test the limits of replication and division coordination using single-cell measurements and nutrient-shift experiments. This leads us to reevaluate the canonical Helmstetter-Cooper cell cycle model. Instead of a strict dependency of division on replication initiation, we instead support the view that both processes are controlled by independent threshold mechanisms.