MRes in Medical Mycology and Fungal Immunology

项目摘要-真菌感染对人类健康造成了巨大的负担，特别是在免疫系统改变的个体中。如果我们要利用这些知识来开发对抗这些感染的新疗法，对免疫系统如何提供对真菌疾病的保护有更深入的了解是至关重要的。我们之前发现，在免疫细胞表面表达的一种关键分子，称为Dectin-1，在抗真菌免疫中起着核心作用。我们随后的研究表明，Dectin-1保护胃肠道免受白色念珠菌感染，白色念珠菌是一种真菌生物，通常与人类有关，但在免疫功能受损的个体中可能导致毁灭性的疾病。值得注意的是，我们发现Dectin-1的缺失导致白色念珠菌感染后的异常免疫反应，导致感染胃肠道中重要功能细胞（称为t细胞）的损失。我们最近确定Dectin-1控制着一组新分子的表达，这些分子参与了这些关键t细胞反应的发展。在这个应用中，我们建议表征这些令人兴奋的新分子的表达和功能，并确定它们如何在胃肠道中促进抗真菌免疫。项目二：适应性预测对一种主要真菌病原体的影响。适应性预测是一种进化机制，微生物在遇到连续的环境条件时已经学会了事件的顺序。当微生物遇到主要的环境输入时，它已经进化到在遇到第二输入之前预先激活针对第二输入的适应性反应。这种机制可以赋予病原微生物显著的选择优势，因为它们为未来的营养变化和免疫附着做好了准备。主要的人类真菌病原体白色念珠菌似乎已经进化出适应性预测，以增强其在人类某些生态位定居的能力。例如，当白色念珠菌细胞接触到血液蒸汽时，它们就暴露在葡萄糖中，葡萄糖会激活氧化应激反应，为随后的吞噬攻击做好准备。此外，酵母菌丝形态的诱导触发了锌和铁清除和毒素念珠菌素合成的激活，从而为真菌在这些必需微量营养素有限的宿主组织中觅食做好了准备。

Project 1: The role of novel C-type lectin receptors in adaptive anti-fungal immunityProject summary - Fungal infections pose an enormous burden on human health, particularly in individuals with altered immune systems. Developing a greater understanding of how the immune system actually provides protection against fungal diseases is critical if we are to use this knowledge to develop novel therapies to combat these infections. We previously discovered that a key molecule expressed on the surface of immune cells, called Dectin-1, plays a central role in antifungal immunity. Our subsequent research revealed that Dectin-1 protects the gastrointestinal (GI) tract from infection with Candida albicans, a fungal organism that is commonly associated with humans, but that can cause devastating diseases in individuals whose immune functions are compromised. Notably, we found that absence of Dectin-1 led to aberrant immune responses following infection with C. albicans, which resulted in a loss of important functional cells, called T-cells, in the infected GI tract. We have recently determined that Dectin-1 controls expression of a novel group of molecules that are involved in the development of these critical T-cell responses. In this application, we propose to characterise the expression and function of these exciting new molecules and establish how they contribute to antifungal immunity in the GI tract.Project 2: : Impact of Adaptive prediction in a major fungal pathogen.Adaptive prediction is an evolutionary mechanism where the microbes that encounter sequential environmental conditions have learned the sequence of events. When the microorganism encounters a primary environmental input, it has evolved to pre-activate the adaptive response against the second input, before it is encountered. This mechanism can confer significant selective advantage to pathogenic microbes as they become primed for future nutritional changes and immune attach. The major human fungal pathogen Candida albicans appears to have evolved adaptive prediction to enhance its ability to colonise certain niches in humans. For example, when C. albicans cells contact the bloodsteam they are exposed to glucose which activates an oxidative stress response that prepares them for subsequent phagocytic attack. Also, the induction of yeast-hypha morphologies triggers the activation of zinc and iron scavenging and toxin candidalysin synthesis, thereby preparing the fungus for foraging in host tissues where these essential micronutrients are limiting.