Uncovering principles of the central dogma of biology: noise, growth robustness, and overabundance

Abstract

The central dogma of biology describes the most essential processes for all living systems to function: the interactions between messenger RNA, DNA, and protein. Each process in the central dogma occurs on the scale of single molecules and is inherently stochastic, leading to noisy gene expression. Protein noise for eukaryotic and prokaryotic cells has been observed experimentally and modeled theoretically, but its significance has not been understood at the fundamental level. Furthermore, theories have not been able to explain the paradox of how gene expression should be optimal after millions of years of evolution, yet observed to be overabundant: produced in excess of what is required for function. This dissertation covers modeling to explore protein noise, and discusses the cellular strategy of overabundance. In addition, I document my development of OmniSegger, a package improving the accuracy of analyses of cellular timelapses and enabling analysis of unusual cell morphologies, which was critical to quantifying overabundance experimentally.