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

越来越多的证据支持使用蜡蛾幼虫作为体内动物部分替代模型，特别是在感染、免疫和炎症相关领域。虽然它们是昆虫，但它们的免疫系统与人类非常相似。如果Galeria能够被优化为模式生物，那么将对科学研究中使用的啮齿动物的数量产生巨大的潜在影响。然而，目前，幼虫在注射细菌或真菌病原体后的健康状况仅通过对它们是否/何时变黑和死亡的粗略评估来监测。在这个项目的第一部分，我们将使转基因幼虫在压力、感染、免疫挑战或炎症状态下发出不同的荧光。我们将点燃他们的巨噬细胞，即免疫系统中四处游荡的细胞，寻找外来病原体并将其吃掉。这将使我们能够测量这种重要类型的细胞在感染前后的运动，从而彻底改变我们可以获得的关于动物和我们对感染的反应方式的信息的数量和类型。该项目的第二个目标是利用这些荧光Galeria幼虫来了解世界上最常见的人类真菌疾病的原因，一种名为白色念珠菌的病原体是如何隐藏自己的免疫系统的。我们知道假丝酵母菌的细胞表面有免疫系统正常识别的东西，但在某些情况下，他们的环境触发了变化，最终掩盖了这一信号。我们将把假丝酵母菌暴露在许多这样的环境中，并询问发光的Galeria巨噬细胞在识别真菌方面的有效性。因此，我们的工作不仅将找出使念珠菌免受免疫系统影响的关键分子信号，有可能确定新的抗真菌药物的候选分子，而且还有可能彻底使用Galeria作为小鼠的替代模型，使数以千计的小鼠免于在未来的科学研究中使用。

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.