Creation and Use of Software for Analysis of Kinetic Proteomic Experiments

Creation and Use of Software for Analysis of Kinetic Proteomic Experiments Bradley C. Naylor Department of Chemistry and Biochemistry, BYU Doctor of Philosophy Proteins are constantly synthesized and destroyed to ensure sufficient functioning proteins to meet cellular needs, a process called protein turnover. Synthesis and degradation are carefully balanced over time to ensure that average protein concentrations do not change drastically. The status quo of the cell, or protein homeostasis, is required for the health of the organism. If protein homeostasis breaks down, serious diseases, such as Alzheimer’s, can result when proteins aggregate instead of being degraded properly. Because protein turnover is the means to maintain protein homeostasis while keeping sufficient functioning proteins, measuring protein turnover is critical to understanding biological processes and disease states. Measuring protein turnover rates on a broad scale is possible using a method called kinetic proteomics, and the improvement of kinetic proteomics is where I have focused the work for this dissertation. In this dissertation, I will review the history and general strategies for performing kinetic proteomics. I will then demonstrate that I have published an open source, user-friendly program for other scientists to use to perform kinetic proteomics data analysis, as well as publishing a novel discovery of key ribosomal subunits being replaced within the lifetime of the ribosome, which was discovered through use of kinetic proteomics. Finally, I will discuss work that is ongoing to improve my software tool for use in human subjects, and work being done to combine kinetic proteomics with other global analysis methods to make novel biological discoveries.

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