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A combined nuclear magnetic resonance and mass spectrometry metabolomics study of Parkinson's disease and Staphylococcus aureus metabolism
Metabolism based research has experienced an exponential growth in interest due to the fact that human diseases are associated with metabolic perturbations. Metabolomics is a valuable approach to study the state of a biological system and obtain mechanistic insights about human diseases. This dissertation describes the development of a combined Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) metabolomics method, and the application of this method to study the mechanisms of Parkinson's disease and investigate the metabolic response of Staphylococcus aureus. Since NMR and MS have complementary strengths and weaknesses, NMR and MS were simultaneously applied to the analysis of the same set of metabolomics samples. Accordingly, sample preparation, data collection and data analysis have been optimized for the integration of NMR and MS metabolomics. Our results demonstrate that an integrated NMR and MS approach significantly improves the coverage, reliability and information content of a metabolomics study. Parkinson's disease (PD) is a multifactorial neurodegenerative disorder derived from interactions between genetic factors, aging and environmental risk factors. In this study, we have revealed that environmental risk factors, paraquat and manganese, impaired the energy metabolism of dopaminergic cells through distinct mechanisms involving the central carbon metabolism. In addition, we investigated the synergic toxicity between α-synuclein, the major component of lewy bodies, and paraquat or manganese. Staphylococcus aureus is a primary cause of hospital-acquired infections. The survivability of S. aureus arises from its capacity to adapt to environment stressors, such as the presence of antibiotics and nutrient limitation. We have illustrated that the transition of S. aureus from a daptomycin-susceptible to a nonsusceptible state was accompanied by a metabolic shift. We investigated the metabolic response of S. aureus when preferred carbon sources (glucose and pyruvate) were restricted, which are similar to the conditions found in staphylococcal abscess. Results from PD and S. aureus metabolomics studies clearly demonstrate that the combined application of NMR and MS is a valuable tool to study metabolism alterations, discover novel molecular mechanisms, and identify potential therapeutic targets for the development of new treatments.
Molecular biology|Toxicology|Surgery|Analytical chemistry
Lei, Shulei, "A combined nuclear magnetic resonance and mass spectrometry metabolomics study of Parkinson's disease and Staphylococcus aureus metabolism" (2016). ETD collection for University of Nebraska-Lincoln. AAI10183301.