Organisms exist in complex and dynamic environments. Facing numerous challenges, microorganisms must continuously monitor environmental changes and adapt to these if they are to survive. For example, the major fungal pathogen of humans, Candida albicans experiences diverse stresses, including temperature fluctuations, oxidative stress and enzymic processes, that cause molecular damage. Post-translational modifications such as phosphorylation play major roles in stress adaptation, for example through activation of MAP kinase pathways and transcription factors such as the heat shock transcription factor, Hsf1. However, other post-translational modifications such as ubiquitination and sumoylation have been relatively understudied. Nevertheless, they are believed to play crucial regulatory roles in many cellular processes including stress adaptation. Therefore, in this study the roles of ubiquitin and SUMO (small ubiquitin-like modifier) have been investigated in C. albicans. Proteomics was used to identify ubiquitination and sumoylation targets, and this was combined with molecular analyses of the UBI4 and SMT3 genes, which encode polyubiquitin and SUMO, respectively. Both ubiquitination and sumoylation were shown to play important roles in morphogenesis, cell division and stress adaptation in C. albicans, including adaptation to heat and oxidative stresses. In addition, the dynamics of heat shock adaptation were examined in C. albicans using a systems biology approach. Hsf1 is known to activate HSP90. In this study, Hsf1 was found to be transiently phosphorylated in response to heat shock, and Hsp90 was found to down-regulate this Hsf1 phosphorylation. This led to the identification of an autoregulatory loop that controls thermal adaptation in C. albicans. A mathematical model of heat shock regulation (constructed in collaboration with Katarzyna Tyc and Edda Klipp) provided novel insights into the regulation of this evolutionarily conserved environmental response and the significance of thermal adaptation during systemic Candida infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:553804 |
| Date | January 2011 |
| Creators | Leach, Michelle D. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=167804 |
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