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Item An omics-based interrogation of disparate microbial systems: multi-omics analysis of a bio-mining archaeon and the effects of arsenic on the E. coli Lipidome(Montana State University - Bozeman, College of Letters & Science, 2023) Fausset, Hunter Lee; Chairperson, Graduate Committee: Brian Bothner; This is a manuscript style paper that includes co-authored chapters.Systems biology represents the next frontier in the elucidation of biochemical mechanisms, disease states, and microorganisms. Rather than approaching individual parts of an organism, such as a specific protein, molecule, or mRNA, a systems biology or "omics" investigation seeks to characterize all proteins, molecules, or RNA simultaneously. This is crucial, because all macromolecules in a lifeform exist in dynamic equilibria with those around them; no one biological process occurs in a vacuum. Omics investigations have ballooned in usage over the last decades due to scientists realizing their power in characterizing complex biological phenomena. This has also been spurred on by advances in technologies enabling the robust elucidation of thousands of molecules at once, particularly benefitting from the modernization of mass spectrometry. This technique can be used to study any number of biological problems including those presented here; a multi-omics investigation into a mineral- eating methanogen and a lipidomic characterization of arsenic exposure in a key member of the gut microbiome, E.coli. Methanosarcina barkeri, a widespread methanogen found in marine sediments, is able to reductively dissolve minerals such as pyrite (FeS2) to satisfy their iron and sulfur requirements. Presented here are two investigations containing transcriptomic, proteomic, metabolomic, and lipidomic analyses, performed in parallel on the same biomass. Together, these experiments suggest that the organism undergoes a significant phenotypic shift in response to changes in just two elements, Fe and S. Overall inferences are echoed in the small molecule analyses; the metabolomes and lipidome of the organism change similarly in to the proteome. Key sulfur equilibria are implied in the process, as are specific lipids, choline, and dethiobiotin. A similar approach was applied to E.coli treated with arsenic, as a proxy for understanding the detoxifcation that takes place in the gut microbiome after ingestion. Marked lipidomic changes were observed in E.coli resulting from treatment, which were dependent both on species of arsenic as well as presence of the Ars operon. As a foundational study, this work answered some and generated many more hypotheses on the biochemical fate of As in microorganisms in the gut microbiome.