No molecule in a living organism exists in a vacuum. Indeed, each interacts with thousands of other molecules. In any given organism, native interactions have been harnessed to achieve cellular objectives. Similarly, other interactions have been avoided. Thus, through evolution, genes and proteins have evolved to increase the chance that a given living system will be perpetuated (Lewis, et al. MSB, 2010). That is, each component has evolved in the context of all other components in the cell or organism and in the environment (Nam*, Lewis*, Science, 2012). Furthermore, their true function occurs in this complex cellular context, and this function may or may not be seen in vitro. While enzyme functions and biomolecular interactions have classically been studied in vitro or in artificial systems (e.g., enzyme assays or yeast 2-hybrid screens), technological and theoretical advances have recently arisen to elucidate the biochemistry of many individual enzymes in parallel in the context of the complex environment of the cell. Over the coming years, I aim to develop and apply systems analyses (Lewis, et al. Nat Rev Microb 2012) and multiplexed high throughput screening technologies for a few key applications to accelerate the characterization of individual proteins, improve the success of synthetic biology and metabolic engineering designs, and provide deep fundamental insights into the molecular basis of life. First, approaches will be developed and applied to characterize the functions of enzyme post-translational modifications and other enzyme-level properties. Second, systems modeling and genome editing will be harnessed to modulate and study complex post-translational modifications, such as glycosylation. Third, computational models of metabolism and protein secretion will be constructed an used for predictive modeling and omics data analysis to drive improvements in biotherapeutic development.

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