High resolution studies to examine the amyloid core and oligomeric intermediates

蛋白质是身体中几乎所有生物过程的基础，通常采用特定的三维结构才能发挥作用。偶尔，一些蛋白质改变其结构并错误折叠，这可能导致它们聚集或聚合形成细长的纤维。这种类型的过程与许多破坏性疾病有关，包括阿尔茨海默氏症和帕金森氏症以及牛海绵状脑病（MSE或“疯牛病”）。在这些疾病中，错误折叠的过程似乎与它们的进展有关。这些聚集体是由人体自身的蛋白质组成的，被称为淀粉样蛋白。这些淀粉样纤维积聚，导致周围身体组织的破坏。我们感兴趣的是什么原因导致正常可溶性蛋白质错误折叠和聚集。为了更好地理解这一点，我们正在研究最终聚集形式淀粉样蛋白的结构。这项工作是使用X射线，电子和计算机处理进行的。我们也在使用一些不同的实验技术来研究聚集的过程。目的是获得淀粉样纤维结构的清晰图像，这将有助于理解是什么导致纤维形成以及为什么它们如此稳定。我们也可以开始设计可以结合和防止纤维形成的药物。

Proteins are fundamental to almost every biological process in the body and usually adopt a specific three-dimensional structure in order to function. Occasionally, some proteins change their structure and misfold and this may lead to them aggregate or polymerise to form elongated fibres. This type of process is associated with a number of devastating diseases that include Alzheimer's and Parkinson's disease and Bovine spongiform encephalopathy (MSE or 'Mad Cow Disease'). In these diseases the process of misfolding appears to be linked to their progression. The aggregates are made of the body's own proteins and are called amyloid. These amyloid fibrils accumulate causing disruption to the surrounding body tissues. We are interested in what causes normally soluble protein to misfold and to aggregate. In order to understand this better, we are looking at the structure of the final aggregated form, the amyloid. This work is carried out using X-rays, electrons and computer processing. We are also looking at the process of aggregation using a number of different experimental techniques. The aim is to gain a clear picture of the architecture of the amyloid fibril and this will help to understand what causes the fibrils to form and why they are so stable. We can also start to design drugs that can bind and prevent fibril formation.