The metabolism in cancer cells is well known to be reprogrammed to adapt the requirement of rapid growth, such as that glucose and glutamine are two largely consumed nutrients for building blocks. Therefore, interior cancer cells of tumors are facing the glutamine deprivation stress which regulates the compartmentalization/polymerization of CTP synthase to maintenance homeostasis through modulating the enzymatic activity. CTP synthase is crucial for cell growth and functions at the rate-limiting step of pyrimidine biosynthesis, and is involving the production of DNA, RNA, and phospholipid. The elevated expression of CTP synthase is associated with the progression of several types of cancer. Recently, assembly of CTP synthase into polymers as filamentous structure was revealed under several physiological conditions in various species, including human cancer cells, bacteria, yeast, and Drosophila. My laboratory has demonstrated that filamentous structure prevents CTP synthase protein from degradation under glutamine deprivation which allows cancer cells obtaining growth advantage after stress relief. Furthermore, histidine-mediated methylation and ubiquitination play crucial roles in the regulation of CTP synthase assembly and the cytokeratin network serves as a depositing compartment for CTP synthase filament in cancer cells. During Drosophila oogenesis, CTP synthase assembly is essential for endo-replication in follicle cells, and CTP synthase activity is required for border cell migration, a collective directional cell migration. Through APEX proximity labeling, we have also revealed many components involving the assembly system, and details of molecular mechanism is under investigation. Here in this grant proposal, we would like to determine the roles of above components involving in CTP synthase assembly by knockdown assay and immunostaining approaches to determine their effects on CTP synthase processes. The molecular mechanisms of CTPS filament formation by these components will be determined. Furthermore, the effects of disruption of CTP synthase assembly by above conditions on cancer metabolism will be investigated by metabolomics analysis. Major in Biology or Chemistry related language proficiency in English online interview is required