The major fungal pathogen, Candida albicans, has a significant impact upon the health of the European population. Candida frequently causes oral and vaginal thrush, and life-threatening infections in intensive care patients. These infections drain European finances through lost working days and extended patient hospitalization. A major goal is to understand how this fungus interacts with its human host and how these interactions contribute to pathogenesis. This will enhance efforts to develop accurate diagnostics for systemic candidiasis. Candida pathogenomics has advanced rapidly in the last decade. Nevertheless, our understanding of fungus-host interactions remains rudimentary. Therefore, our Grand Challenge is to exploit advanced new tools to accurately capture the spatial and temporal regulation of fungal molecular responses in lesions during disease progression. My laboratory is uniquely placed to address this challenge using a powerful combination of new, state-of-the-art technologies. Laser capture microscopy, ultrasensitive microarray technologies and 2D-MALDI-ToF mass spectrometry will be used to define the C. albicans transcriptome and infectome, both spatially and temporally, across fungal lesions during disease progression. C. albicans infections will be imaged with a novel ultrasensitive reporter to confirm the dynamic regulation of specific cellular processes during disease progression. Then precise molecular tools will be used to establish the relative contributions of these processes to the infection process, and to explore candidate diagnostic targets identified during this programme. This will dramatically advance our understanding of fungus-host interactions and will identify potentially novel biomarkers of deep-seated systemic candidiasis.
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