To (i) extend and refine existing in vitro and ex vivo commensal and infection models for C. albicans and C. glabrata; (ii) to dissect the different stages of infection; (iii) to characterize the fungal and host transcriptional profiles during infection; (iv) to identify stage-specific marker genes of C. albicans and C. glabrata infection; (v) to identify and characterize genes that are required for pathogenicity of C. albicans and C. glabrata.
In collaboration with ESR5 and 6 (P3), ESR9 will monitor the interaction of C. albicans and C. glabrata with vaginal and intestinal epithelial, endothelial cells and blood cells, and will dissect the infection process. RNA-seq will be used to determine the stage-specific transcriptional profile of the pathogen and the host. Genes associated with the different stages of infection will be identified using RNA-seq and compared to data obtained during infections with other species (P3) to identify common and species-specific signatures. QRT-PCR will be used to validate results. Candidate marker genes will be developed into prototype diagnostic tools. Candidate genes will be disrupted and their roles in infection analysed. Furthermore, to identify genes crucial for pathogenicity, mutant strains from a collection of >1800 C. albicans and > 1000 C. glabrata knock out strains (available at P6) will be monitored in the established infection models.