Sugar coated armour: exploring UDP galactopyranose mutase (UGM) as a potential antifungal target

现代医学治疗，包括癌症治疗和器官移植的进步，使患者由于免疫系统减弱而极易感染。真菌感染在这些患者中往往是致命的。烟曲霉是一种真菌，产生广泛存在于环境中的孢子。在健康人中，吸入的孢子是无害的，并被免疫系统消除，但在某些群体中，包括那些有肺部问题的人，它们会引起疾病。最严重的是“侵袭性真菌病”，它会导致危及生命的感染，而这种感染是出了名的难以诊断和治疗。我们对这一重要结构的了解仍有许多空白。这些问题需要科学家和临床医生使用新的实验室方法来解决。在MRC的帮助下，我试图提高我们对负责产生一种新型糖的蛋白质（酶）的结构和功能的理解，并设计一种识别小分子以阻止其功能的方法。这项工作是最终改善真菌感染日益加重的诊断测试和治疗的关键第一步。

Modern medical treatments including advances in cancer therapy and organ transplantation render patients highly susceptible to infection due to a weakened immune system. Fungal infections are often fatal in these patients. Aspergillus fumigatus is a fungus that produces spores found widely in the environment. In healthy people inhaled spores are harmless and eliminated by the immune system but in certain groups, including those with existing lung problems, they cause disease. The most serious, ‘invasive Aspergillosis‘, leads to life-threatening infections that are notoriously difficult to diagnose and treat.A shield of sugar-coated armour makes up the cell wall surrounding and protecting the fungus. There are still many gaps in our knowledge of this important structure. These need addressed by scientists and clinicians using novel laboratory based approaches. With assistance from the MRC, I seek to improve our understanding of the structure and function of a protein (enzyme) responsible for producing one of the novel sugars and to devise a way of identifying small molecules to block its function. This work is a crucial first step towards ultimately improving diagnostic tests and treatments for the increasing burden of fungal infections.