ELUCIDATING GENES AND PATHWAYS REQUIRED FOR MEIOSIS IN YEAST AND MAMMALS
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Meiosis is an important developmental program that determines the quality and quantity of the next generation. The process is conserved in a range of organisms from unicellular budding yeast to multi-cellular mammals. Errors during this process can lead to infertility, miscarriages, or birth defect.The main goal of the dissertation is to develop new mathematical models and machine learning tools to study the biological networks and pathways involved in meiosis. These tools would be further used to indentify important genes and cellular interactions controlling meiosis. The potential meiosis specific genes would be studied further and experimentally verified to solve problems related to infertility. The study would enhance better understanding of meiosis and open up avenues for pathway and genetic engineering. My thesis addresses four related projects on meiotic process in yeast and mammals:1.A metabolic network specific for the Saccharomyces cerevisiae meiosis is constructed and used to indentify the cellular objective of the cell. Novel sporulation deficient genes were indentified that contribute to the efficiency of the meiosis process. 2.The genetic regulation is an important factor that controls the precise expression of important gene that initiate the meiosis process. Feedback loops forms a robust mechanism that assures a rapid and complete transition into meiosis. We formulated a dynamic model to understand how feedback loops control yeast meiotic initiation. 3.The expression and localization of potential meiosis specific genes were identified using support vector machine learning methods. Groups of novel genes associated with male and female meiosis process were correctly identified.4.The cellular behaviors in mammalian germ cells are coordinated to produce testicular morphology and generate male gametes. We aim to identify the cellular behaviors that have major influence on the developmental process. We can understand cellular processes in normal spermatogenesis and predict the casual cellular events in the various spermatogenic defects. Overall, this thesis work contributes to the development of nethodology to indentify important genes and processes that contribute to the success of meiosis process.