From ‘molecular pattern’ to ligand structure and function – the origins of antifungal immunity

We aim to resolve the chemical identity of molecular patterns that trigger antifungal immunity, and to exploit this information to understand immune evasion during disease progression and inform the future development of improved antifungal diagnostics. Our collaborative team will address this critical challenge through our complementary expertise in state-of-the-art high throughput approaches involving carbohydrate chemistry, antifungal immunobiology, genomics and precision reverse genetics. Our immune defences provide protection against the constant threat of infection by opportunistic fungal pathogens, and pathogen recognition is a vital first step in these defences. We previously defined the relative contributions of major pathogen-associated molecular patterns (PAMPs) in the cell wall of Candida albicans that are recognised by pattern recognition receptors (PRRs) to illicit immune responses. We also discovered that this major fungal pathogen exploits host signals to activate PAMP masking strategies and evade immune recognition. Critical questions emerge from these studies. (1) What are the chemical identities of the actual PRR-ligands within PAMPs? (2) How does the fungus modulate PRR-ligand exposure as it adapts to host niches? (3) How does this modulation impact fungal virulence and anti-fungal immune responses? Answering these questions, which underlie fungal recognition phenomena, will provide invaluable opportunities for diagnostic and therapeutic developments.