The opportunistic human fungal pathogen, Candida albicans causes a wide range of serious disease manifestations, especially in individuals with an impaired immune system. The ability of C. albicans to successfully infect almost every anatomical niche of the human host is both a serious medical problem and an interesting biological property. It is known from in vitro transcriptional profiling that the organism rapidly alters gene expression in response to changing environments; however, very little is known of gene expression patterns in vivo. In addition, a significant proportion of C. albicans genes expressed during infection have no known function. This study will address these two problems in the following ways. Firstly, the transcriptional profile of C. albicans interaction with the host during three distinct models of infection (oral, liver and blood) will be analysed to determine whether C. albicans responds using general transcriptional mechanisms during infection or whether responses are specific depending on the anatomical niche. This transcriptional analysis will then form the basis of a systematic disruption strategy to elucidate the function and role of unknown function genes. Relevant deletion mutants will be generated using a rapid PCR based method and tested for host-interaction using established models of infection. This characterisation will elucidate the function of unknown function genes during infection and describe de novo properties of C. albicans biology. Furthermore, by testing mutants in more than one model of infection it will be shown whether a gene upregulated specifically during one type of infection has significance in another.
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