Proteomic and metallomic responses of Saccharomyces cerevisiae to perturbations of environmental metal availability

Abstract

Metal ions are essential for many biochemical processes inside all living cells. Although decades of careful experimentation in various model systems has led to the discovery of numerous functions of the essential metals, systematic studies that investigate the interactions of metal ions with various components of living cells remain scarce. Therefore, this work was designed and conducted as a systems-scale experiment to determine the consequences of a perturbation in extracellular metal availability on the growth rate, intracellular metal concentration and protein abundance of a simple eukaryote - Saccharomyces cerevisiae. The results reveal novel inter-dependencies of the concentration of each essential metal on the availability of the others and system-wide changes in protein abundance that are specific enough to separate most proteome samples in accordance with the perturbation caused and can be used to generate novel hypotheses about protein function and protein-protein interactions. The data generated by this work comprise a novel resource of high quality and impact that will be immensely useful in the design and interpretation of future investigations of the role of each essential metal in various cellular processes. It paves the way for the inclusion of metal ions and their interactions with other biomolecules in standard models (and pedagogy) of cellular biochemistry. This thesis describes the discovery that perturbations in metal availability of essential metals can have a system-wide impact on cellular physiology, as exemplified by the differential expression of numerous metal-binding proteins, proteins mapping to multiple metabolic pathways, and the identification of ohnolog pairs that show negatively correlated abundance patterns when S. cerevisiae cells are cultivated in a range of perturbed environmental metal concentrations