Making and breaking the cell walls of fungal pathogens. (360G-Wellcome-101873_Z_13_Z)

The cell wall of fungal pathogens determines their pathobiology and immunological signature. It is the ideal target for chemotherapies and immunotherapies because all the major cell wall components are essential and fungal-specific. My vision is to innovate and inform therapeutic strategies through an understanding of how the cell wall is assembled and recognised by the immune system. My group are world leaders in the analysis of the major human pathogen Candida albicans, and have made fundam ental advances in cell wall biology. These foundations enable two major new research questions to be addressed, each with translatable outcomes. (i) What are the key assembly processes and functions of the extended gene families that articulate cell wall assembly? To answer this, I will exploit recent advances in C. albicans genetics to pioneer forward genetic methods using recently discovered haploid strains. Novel screens, phenotyping methods and in vitro synthetic biology approaches w ill be deployed to dissect the functions of key families of cell wall genes. (ii) What is the fine chemical structure of cell wall molecules that stimulate, attenuate and imprint the innate and adaptive responses of the immune system? I will use novel, bespoke reagents and combinations of host and pathogen functional analysis tools to study the key immunologically relevant cell wall glycoconjugates. These complementary research questions will result in major advances in our understanding of therapeutically tractable targets of the cell wall, and will inform the design of new generations of therapeutics and diagnostics.