Book Description

How do we respond to our environment? How much does our environment drive our very form, our physical shape? These are fundamental questions that biology must grapple with on all scales of life. Understanding how the shape of an organism is formed, how it is maintained, and how it interacts with external stresses is key to understanding its strengths, limitations, and what it could become. My thesis examines a portion of the complex relationship between organism and environment by studying the physical changes bacteria undergo in both friendly and hostile environments, using the well-studied model organism Escherichia coli. In Chapter one, I will introduce the relevant bacterial physiology necessary for understanding cellular growth and division. I will also define the structural and molecular determinants of cell shape in bacteria, and then examine what is known about how environmental conditions impact cell shape. In chapter two, I will start at the protein level, examining a key protein in the cell division machinery, FtsZ, and its relationship to inhibitors that induce cell death. In chapter three, four and five, I will move to larger cellular structures and discuss how genetic or external perturbations effect the integrity of the bacterial cell wall, the key macromolecule in cell shape determination. In chapter six, I will move from single molecules to molecular networks: I will examine a stress response pathway, the Rcs pathway, and its connection with perturbations to cell width and its influence on cell length. I will show how these observations again relate to the interaction and regulation of the cell wall synthesis machinery governed by cytoskeletal proteins MreB and FtsZ, respectively. In chapter seven, I move finally from single cell behavior to the behavior of cell populations under stress. Specifically, I will utilize previous work examining the relationship between increased cell size and fitness as the basis for generating a cell shape mutant library. I then used this library in a high-throughput chemical genomics screen to further characterize the types of stressful environments in which size plays a key role in fitness, revealing evolutionary pressures on cell shape. I will conclude in chapter eight by re-examining the fundamental questions posed at the beginning of this chapter and reflect on how this work moves us a step forward in illuminating the complex and varied ways in which organisms interact and are changed by their environment.