High resolution studies to examine the amyloid core and oligomeric intermediates

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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.