THE ROLE OF EXTRACELLULAR VESICLES IN REGULATING DIVISION OF LABOUR IN FUNGI

点击翻译按钮获取中文摘要

Many animal species use teamwork in order to maximize fitness through Division of Labour: for instance, via the allocation of guard duties and food gathering duties to different individuals in social insects. However, a recent and surprising discovery has been that single-celled microbes are also capable of Division of Labour. Moreover, such behaviours often underlie important processes such as antimicrobial resistance in bacteria.We have recently discovered a novel Division of Labour behaviour in the fatal fungal pathogen Cryptococcus gattii. Upon entry into the host, individual fungal cells communicate in order to adopt two different fates: some individuals stop growing and become quiescent "guard cells", which then protect the other "proliferative" individuals from being killed by the host. This enables the fungus to grow rapidly and overwhelm the host; something that neither fungal cell type can achieve alone.The mechanism by which this Division of Labour occurs at the molecular level is completely unknown. However, we have recent data demonstrating that the cell-to-cell communication it entails is carried out by extracellular vesicles, which act as long-distance "carrier pigeons" to enable fungal cells to coordinate their behaviour over large distances. The aim of this proposal is therefore to dissect, for the first time, the nature of this novel virulence mechanism by:1. discovering how extracellular vesicles coordinate fungal behaviour2. characterizing the contents of these vesicles3. identifying how these vesicles are transported between fungi and their surrounding host cells4. revealing how host cells respond to this fungal manipulation.In doing so, we aim to reveal a completely new type of pathogenesis mechanism in an important human and animal disease. In addition, since i) Division of Labour mechanisms operate in a diverse range of microbes, and ii) extracellular vesicles are known to be shed by a large number of bacterial and fungal species, it is possible that the processes we will unveil within this project may provide a broad paradigm for understanding Division of Labour across the full breadth of microbiology.