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Title: MicroRNA biogenesis and cytoophidia in Drosophila melanogaster
Author: Azzam, Mohd Ghows Bin Mohd
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2012
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This thesis contains two separate projects. The first project involves the study of Argonaute 1 (Ago l) which is a member of the ArgonautelPIWI protein family involved in small RNA-mediated gene regulation. In Drosophila, Agol plays a specific role in microRNA (miRNA) function. Previous studies have demonstrated that Ago 1 regulates the fate of germline stem cells. However, the function of Ago 1 in other aspects of oogenesis is still elusive. Here, the function of Ago 1 was analysed in the female germline and follicle cells. The Ago 1 protein is enriched in the oocyte and also highly expressed in the cytoplasm of follicle cells. Clonal analysis of multiple ago1 mutant alleles shows that mutant egg chambers often contain only eight nurse cells and lack an oocyte which is phenocopied in dicer-I , pasha and drosha mutants. This implies a general role of miRNAs in this process. Further analysis of the clones shows that Agol, Dicer-l, Drosha and miR-l24a play a role in maintaining follicle cell integrity. Additionally, it was found that Ago 1 protein levels were lowered when miRNAs were not present and that overexpression of miR-124a increased the steady state level of Ago 1 proteins. These were believed to be the effect of Ago 1 protein stability. In the meantime, a second project was carried studying a novel filamentous structure called cytoophidia which contains CTP synthase (CTPS) was analysed. Previous studies have shown that the cytoophidia is prominent in the egg chambers but how and why CTPS forms cytoophidia is still unclear. Here, the different CTPS isoforms were analysed and only CTPS isoform C was found to form cytoophidia. This isoform could also induce cytoophidia formation in other tissues that does not have obvious cytoophidia formation. Then, it was identified that the first 56 amino acid of CTPS isoform C is the important region for cytoophidia formation. Furthermore, ctps mutants were generated and analysed. CTPS mutations caused lethality during the larval stage and when maternal contribution was removed, lethality was seen during embryogenesis.
Supervisor: Liu, Ji-Long Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available