Systems level decomposition of adaptation to metabolic perturbation
Much progress has been made in establishing the causality of mutations that occur during adaptive laboratory evolution (ALE) on organism physiology. In contrast, little progress has been made in detailing the mechanisms and overarching principles of evolution that govern the adaptive process. This dissertation describes the following three aims that sought to address the technical and scientific challenges required to better understand adaptive evolution in micro-organisms. First, an improved method to quantify intracellular metabolites from sampling and extraction to acquisition and quantitation was developed and validated. Second, an improved method to measure intracellular fluxes from sampling and extraction to acquisition and modeling was developed and validated. And finally, aims 1 and 2 were applied in order to uncover system level principles and mechanistic level network functions that were required to adapt to major metabolic perturbation.