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Title: Freethinkers, a novel, and 'Inventing history: how do research, imagination and memory fuse creatively in the writing of an historical novel?'
Author: Richardson, Heather Evelyn
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2014
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The eukaryotic cell cycle is the central molecular oscillator underlying tissue growth. Although previous studies have analyzed global cell cycle-associated transcription using unicellular systems, precisely how cell cycle-dependent processes are integrated in multicellular development in vivo remains unclear. One multicellular context-specific cell cycle event is the Interkinetic Nuclear Migration (IKNM), a conserved process by which proliferating nuclei translocate to the apical epithelial surface ofthe epithelium to execute mitosis. How c,ell cycle progression is linked with IKNM remains poorly understood. Here, I report the global cell cycle-associated transcriptomes of Drosophila wing disc epithelial cells (multicellular system) and cultured S2 cells (unicellular system). With an integrative F ACS-microarray technique, we identified over 600 genes with periodic express ion profiles in each context. Intriguingly, despite the common periodic genes identified, we also identified 200 genes 'periodically expressed only in the wing disc cells, including many core cell cycle components. I further explored the function of those wing disc periodic genes by tissue-specific RNAi knockdown. Combining flow cytometry and confocal imaging, I defined 107 pe:rl'odk genes that control wing growth, wherein 35 periodic genes control cell cycle progression in the developing wing but not in S2 cells (compared with results from S2 RNAi screens). In addition to several novel regulators of mitotic cell size and chromosome segregation, I also identified two novel wing disc-speCific periodic genes, knockdown of which disrupt IKNM. Strikingly, in both cases, disconnecting nuclei positioning with mitosis does not disrupt cell cycle progression per se. One of the IKNM genes is a potential lincRNA, which may regulate the expression of kinesin-like protein, Klp54D, and is required for normal centriole function. Taken together, my study provided a global functional perspective on cell cycle regulation in vivo, and identified numerous novel periodic genes that control growth, cell proliferation and IKNM in the epithelial context. IV ..
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available