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Abstract

Small molecule metabolites are the last, often underappreciated level in the central dogma of molecular biology. Small molecules have become more appreciated for both their functional role and as a readout of the phenotype of a biological system. Metabolomics is the approach by which we identify and measure these small molecules. Nuclear Magnetic Resonance (NMR) is a common technique for performing metabolomics studies that possess several unique advantages for making such measurements. As the field of metabolomics has grown, so has the application of metabolomics in cell models of disease. Additionally, recent developments in cell-based therapeutics have also created a need for understanding and predicting function and product quality, which metabolomics of cell cultures is also well suited to provide. In this dissertation I will introduce the concepts and utility of NMR metabolomics to cell systems, then show how I have leveraged NMR metabolomics to gain a novel understanding of metabolic adaptations in cell models of cancer and rare genetic disease, as well as the measurement of culture media metabolites by NMR to develop a platform for predicting functional outputs of therapeutic cell products.

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