Structure and regulation of the cytoplasmic membrane complexes formed during signal transduction by the Toll-like receptors

人类已经进化出复杂而有效的方法来对抗由细菌和病毒等微生物引起的感染，免疫系统。有时免疫系统会出错，这可能会导致严重的疾病，如类风湿性关节炎和糖尿病。我们的研究旨在从分子水平上了解免疫系统的细胞如何识别微生物，以及这些细胞对引起发烧和疲劳等感染的常见症状作出反应的方式，并产生对抗入侵微生物的特异性抗体。在这个项目中，我们将研究免疫系统细胞对感染期间某些类型细菌释放的强大毒素（如内毒素或LPS）的反应方式。虽然对内毒素的正常反应是对抗感染的重要组成部分，但它可在严重败血症患者中引起称为内毒素休克的高度危险的状况，并且这种病理反应经常导致器官衰竭和死亡。事实上，仅在欧洲，内毒素休克每年就造成约135000人死亡。拟议的研究应该阐明为什么内毒素可以在某些条件下产生有益的反应，而在其他条件下产生破坏性反应。

Humans have evolved complex and effective ways of fighting infections caused by microbes such as bacteria and viruses, the immune system. Sometimes the immune system goes wrong and this can cause serious diseases such as rheumatoid arthritis and diabetes. Our research aims to understand at a molecular level how the cells of the immune system are able to recognise microbes and the ways in which these cells respond to cause the familiar symptoms of an infection such as fever and tiredness, and to generate specific antibodies that fight the invading microbes. In this project we will study the way in which immune system cells respond to a powerful toxins, such as endotoxin or LPS, released by certain types of bacteria during an infection. Although normal responses to endotoxin are an important part of the fight against infection, it can cause a highly dangerous condition called endotoxic shock in patients with severe septicaemia and this pathological response frequently causes organ failure and death. In fact endotoxin shock is responsible for about 135000 deaths every year in Europe alone. The proposed studies should shed light on why endotoxin can produce a beneficial reaction in some conditions and a damaging response in others.