Dissection of the Leishmania mannogen biosynthetic pathway: beta 1-2 mannan in pathogens and beyond

大多数生物体以葡萄糖基多糖的形式储存能量储备；比如人体中的糖原，植物中的淀粉。但有些生物使用更不寻常的碳水化合物储存形式。作为一个国际团队的一部分，我们刚刚发现了利什曼原虫——例如，白蛉传播利什曼病的病原体——以一种被称为“甘露聚糖”的不寻常多糖的形式储存能量。这种能量储存的形成对寄生虫的传染性至关重要。这笔拨款将用于调查利什曼原虫是如何制造和分解甘露聚糖的。我们将详细分析酶（自然界的催化剂）是如何被用来储存这种能量的，并看看酶是否可以被抑制，以便为潜在的新型抗寄生虫剂提供学术基础。每年约有200万人感染这种使人衰弱的疾病，其中约7万人将死亡。我们的研究将为了解这种世界主要寄生虫的新陈代谢提供见解。除此之外，我们的工作表明细菌中存在类似的酶，我们的工作将探索它们的结构和功能，并有望在一系列细菌中发现新的生化途径。

Most living organisms store energy reserves in the form of glucose-based polysaccharides; glycogen in humans, and starch in plants, for example. But some organisms use more unusual forms of carbohydrate storage. As part of an international team, we have just discovered the Leishmanial parasite - the causative agent of the sandfly-transmitted Leishmaniases, for example, stores energy in the form of an unusual polysaccharide termed 'mannogen'. Formation of this energy store is essential for the parasite infectivity. This grant will investigate how mannogen is made and broken down by Leishmania. We will dissect exactly how enzymes, nature's catalysts, are used to make this energy store and see if the enzymes can be inhibited in order to provide the academic foundation for potential new anti-parasite agents. Around two million people each year contract this debilitating disease and around seventy thousand will die. Our research will provide insights into the metabolism into this major world parasite. Beyond this, our work shows that similar enzymes exist across bacteria, our work will probe their structure and function and hopefully identify new biochemical pathways in a range of bacteria.