Spatial analysis of gene expression in fungal infections

About This Grant

Summary This research proposal seeks to incorporate spatial transcriptional analysis into the study of host- pathogen interactions, with a focus on fungal infection biology. Currently, most gene expression analyses of organs infected with fungal pathogens rely on `bulk' approaches, i.e. measurements derived from homogenized tissue samples. Cell-to-cell variability in gene expression, a rampant phenomenon observed in populations of clonal cells from all domains of life, cannot be recorded with such approaches. Likewise, critical information on the spatial configuration of the infection site is lost with these methods. The proposal leverages a method recently developed in my laboratory which enables the visualization and quantification of fungal mRNA molecules in infected mouse organs at single-cell resolution. We propose to apply and expand this technique to investigate pathogenesis-related traits in the human fungal pathogen Candida albicans. Specifically, the project will examine how host tissue microenvironments influence the expression of C. albicans virulence genes. By providing single-cell resolution to fungal virulence gene expression analyses, the proposal introduces a platform to address long-standing questions on the role of fungal cell heterogeneity in colonization and infection of the mammalian host.