Engineering Galleria Mellonella as a model for infection, immunity and inflammation

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Growing evidence supports the use of the larvae of the waxmoth, Galleria Mellonella, as an in vivo animal partial replacement model, particularly in the related fields of infection, immunity and inflammation. Although they are insects, their immune system is very similar to humans. There is huge potential impact on the number of rodents used in scientific research, if Galleria can be optimised as a model organism. However, currently, the health of larvae after injection with bacteria or fungal pathogens is monitored only by a crude assessment of whether/when they turn black and die. In the first part of this project, we will make transgenic larvae that glow (fluoresce) differentially under stress, infection, immune challenge or inflammatory status. We will light up their macrophages, the cells in the immune system that wander around, looking for foreign pathogens and "eating them". This will allow us to measure the movement of this important type of cell before and after infection, revolutionising the amount and type of information we can obtain about the way animals, and we, respond to infection.The second aim of the project is to use these fluorescent Galleria larvae to understand how the most common cause of human fungal disease in the world, a pathogen called Candida albicans, hides itself from our immune system. We know that Candida has something on their cell surface that the immune system normally recognises but that, in some cases, their environment triggers a change that ends up masking this signal. We will expose Candida to many of these sorts of environments and ask how effective the glowing Galleria macrophages are at recognising the fungus. Our work will therefore not only figure out the key molecular signals that mask Candida from the immune system, potentially identifying candidate molecules for new anti-fungal agents, but also has the potential to revolutionise the use of Galleria as mouse replacement model, saving many thousands of mice from being used in scientific research in the future.