Single cell growth and division models

Abstract

Cells coordinate their growth and division to maintain a finite size. They undertake important processes within a cell cycle such as DNA replication. How these processes such as cell growth, DNA replication, and cell division are coordinated with each other remains an open question. Advancements in experimental techniques in the last decade have allowed us to obtain high-throughput data at the single-cell level. In this dissertation, I analyze the cell length data from these experiments to find how single-cell bacteria grow and what controls the start of DNA replication and the cell division event. First, I explain why cell length is an appropriate cell characteristic to study cell division. Next, I test various data analysis methods used to probe the mode of growth of a single cell. I apply these validated methods to experimental data in Escherichia coli and Mycobacterium tuberculosis and find that these bacterial species have different forms of growth- E. coli grows super-exponentially while M. tuberculosis grows predominantly linearly. Further, I hypothesize cell cycle models that differ in whether the DNA replication process plays a role in determining when the cell divides. I find that DNA replication’s role in determining when cell division happens in E. coli is growth rate dependent. I also discuss the molecular basis of these processes that affect cell division. The dissertation aims to forward the phenomenological understanding and serves as a foundation for a molecular understanding of the bacterial cell cycle.