Modeling heterogeneity in the microbial world

Stochastic gene expression, metabolism

Cole, Jr., John Andrew

关键词: Stochastic gene expression, metabolism;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/99301/COLEJR-DISSERTATION-2017.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

No two living cells are identical. Like tiny, squishy snowflakes, even seemingly identical cells (belonging to isogenic populations, and living under macroscopically similar conditions), will experience variations in their local microenvironments and in the numbers of gene copies, messenger RNAs, proteins, and other macromolecules that constitute their make up, and importantly, dictate their behavior. In this thesis I will employ the methods of systems biology, stochastic simulation, and mathematical analysis to investigate some of the causes and outcomes of this type of biological variability in the microbial world. This document is divided into four main chapters. The first focuses on how the stochastic expression of metabolic enzymes affects the growth and metabolic pathway usage of individual Escherichia coli cells. The second chapter deals with how E. coli cells in colonies diverge behaviorally as a function of their location, and how they naturally tend to cooperate in a previously unknown form of crossfeeding. Finally, the third and fourth chapters deal with details of how gene expression stochasticity itself arises, with an eye toward the effects that DNA replication have on mRNA and protein statistics (and what that means for interpreting single molecule experiments).