MRes in Medical Mycology and Fungal Immunology

医学真菌学和真菌免疫学硕士

• 批准号: 2304742
• 金额: --
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2304742
• 关键词: MRes; Medical; Mycology; Fungal; Immunology

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.

项目一：新型C型凝集素受体在适应性抗真菌免疫中的作用项目摘要-真菌感染对人类健康造成巨大负担，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新的治疗方法来对抗这些感染，那么更好地了解免疫系统实际上如何提供对真菌疾病的保护至关重要。我们之前发现，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可以保护胃肠道（GI）免受白色念珠菌的感染，白色念珠菌是一种通常与人类相关的真菌，但可能会导致免疫功能受损的个体发生毁灭性疾病。值得注意的是，我们发现Dectin-1的缺失导致感染C.白色念珠菌，这导致在感染的胃肠道中的重要功能细胞，称为T细胞的损失。我们最近确定，Dectin-1控制一组新分子的表达，这些分子参与这些关键T细胞反应的发展。在这个应用中，我们提出研究这些令人兴奋的新分子的表达和功能，并确定它们如何有助于胃肠道中的抗真菌免疫。项目2：：适应性预测在主要真菌病原体中的影响适应性预测是一种进化机制，在这种机制中，遇到连续环境条件的微生物已经学习了事件的顺序。当微生物遇到主要环境输入时，它已经进化为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。人类主要的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壁龛中定植的能力。例如，当C.白色念珠菌细胞接触血流，它们暴露于葡萄糖，葡萄糖激活氧化应激反应，使它们为随后的吞噬攻击做准备。此外，酵母菌丝形态的诱导触发锌和铁清除和毒素candidalysin合成的激活，从而准备在宿主组织中觅食，这些必需的微量营养素是有限的真菌。