Structural investigation of protein:protein interactions within the membrane attack complex of complement

我们的目的是找出为什么有些人容易受到细菌感染，比如脑膜炎。当我们的免疫系统检测到感染生物体的存在时，它会触发快速反应，发现、杀死并清除这些生物体。补体是我们免疫系统的一个分支的名称，补体反应的一个显著特征是它能够通过在细胞膜上穿出许多大洞，使它们渗漏，从而杀死生物体。这些孔是由五种不同的蛋白质组成的，它们以有组织的方式快速自组装，形成管状的孔，称为膜攻击复合物（MAC），穿过细胞膜。我们正在分别制造MAC蛋白的组成部分，以确定它们各自的形状和化学特性，并研究它们如何组合在一起。我们的目标是发现哪些特征对MAC组装过程和保持稳定的孔隙是重要的。然后我们可以确定如何刺激或抑制毛孔的组装和稳定性。这些知识可以用来指导药物的设计，以对抗细菌感染或防止不必要的补体攻击，例如在自身免疫性疾病中，一个人的免疫系统攻击自己的身体，或移植手术后防止器官排斥。

Our aim is to find out why some people are susceptible to bacterial infections, such as meningitis.When our immune system detects the presence of infecting organisms, it triggers a rapid response to find, kill and remove the organisms. Complement is the name of one arm of our immune system and a remarkable feature of the complement response is its ability to kill organisms by piercing their cell membranes with many large holes, causing them to leak. These holes are made of five different proteins that rapidly self-assemble in an organised manner to form tube-like pores, called Membrane Attack Complexes (MAC), that pass through the cell membranes.We are making the component parts of MAC proteins separately to determine their individual shapes and chemical characteristics, and to work out how they fit together. We aim to discover what features are important for the process of the MAC assembly and for maintaining a stable pore. Then we can determine how to stimulate, or to suppress, the assembly and stability of the pores.This knowledge can be used to guide the design of drugs either to fight bacterial infections or to prevent unwanted complement attack, for example in auto-immune diseases, where a person’s immune system attacks their own body, or after transplant surgery to prevent organ rejection.