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Title: The assembly of CTP synthase into the cytoophidium in Schizosaccharomyces pombe
Author: Zhang, Jing
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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It is widely known that two factors can affect the activity of enzymes, the total molecular number in the cell or a subcellular compartment, or the activity of the molecule itself. Thus, spatial compartmentalization, such as sequestering enzymes in subcellular organelles, becomes an important method of regulating enzymes. Recently, several metabolic enzymes have been identified being able to form filamentous structures in vivo, indicating a new mode of enzymatic regulation. One of the representatives among these self-assembly enzymes is cytidine-5'triphosohate synthase (CTPS), a critical metabolic enzyme involved in de novo CTP synthesis. Although the catalytic function of CTPS has been well studied over decades, it is only recently observed that CTPS is able to self-assembly into filamentous structure, so called the cytoophidium (plural version as cytoophidia). The cytoophidium is evolutionarily conserved from bacteria (Caulobactor crescentus and Escherichia coli), yeast (Saccharomyces cerevisiae), fruit fly (Drosophila melanogaster) to rat (Genus Rattus) and human (Homo sapiens) cells. In this thesis I describe using Schizosaccharomyces pombe (shortened as S. pombe) as a model to study the cytoophidium. Taking advantages of the S. pombe easily manipulated genome, I developed a set of basic protocols of manipulating fission yeast in our lab and established several libraries including hundreds of primers, plasmids and S. pombe strains, and therefore starts the yeast research system in our lab. Primary observation was taken in S. pombe, including morphology observation, drug tests and live imaging, to have a general description for cytoophidia. The critical metabolic pathway, MAPK pathway and TOR pathway, were identified as the potential candidates involved in cytoophidia regulation. Several heat shock proteins were proved related with cytoophidia management. In addition, a novel phenomenon was observed that, unlike most other proteins, CTPS remain in filamentous form and are distributed asymmetrically during cytokinesis in S. pombe. All these experimental data can serve as a good primary exploration and provide a basic platform for future cytoophidia research in S. pombe.
Supervisor: Liu, Ji-Long ; Bassett, Andrew Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available