Subcellular sequestration of proteins within membrane bound compartments is widely acknowledged to be an important mode of enzymatic regulation. Recently a novel paradigm for metabolic enzyme compartmentalisation has become apparent with the identification of several proteins which are able to form filamentous structures in vivo. Multiple studies independently identified the essential de novo pyrimidine biosynthesis enzyme CTP synthetase as a major constituent of a novel filamentous structure which has been termed “the cytoophidium”. Cytoophidia have been observed to form in multiple organisms including bacteria (C. crescentus), yeast (S. cerevisiae) and fruit fly (D. melanogaster) as well as in human cultured cells. In this thesis I describe the development and results of a high throughput genomescale screen to identify factors involved in cytoophidia biogenesis. Observations of tissue specific CTPS distribution lead to the identification of the well-conserved growth regulator dm/dMyc as an essential factor for CTPS regulation in vivo. These results provide new insights into the coordination of cellular growth and metabolic regulation during normal development and indicate the potential of CTPS/cytoophidia as a future therapeutic target.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:618478 |
| Date | January 2014 |
| Creators | Aughey, Gabriel N. |
| Contributors | Liu, Ji-long |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:7561b71c-9824-4358-8175-2b8bb4a7196e |
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