Impact of the amyloid in atherosclerotic plaques

Amyloid is insoluble fibrillar protein deposited in the extra cellular space. The resulting heterogeneous group of disorders is called amyloidosis. The fibril formation may be lethal through organ failure because of the persistence and accumulation of the deposits or by a toxic mechanism. Today about 20 different proteins are deposited in tissues as amyloid and associated with disease, for example Alzheimer´s disease and type-2-diabetes. My project is an investigation of the impact of the apolipoprotein A-1 amyloid in atherosclerotic plaques. Understanding the relationship between amyloidosis, atherosclerosis and inflammation may give rise to new knowledge of the pathogenesis of an important disease and perhaps to new medicines for treatment of vascular diseases in the future.

An investigation of apolipoprotein A-1 (apo A-1) as an amyloid protein can give insight to other amyloid diseases. Because this is a new PhD project a lot of different experiments have to be performed for example we would like help with understanding the fibril formation of Apo A-1. It is not known how normal proteins are cleaved to smaller fragments that starts making fibrils and later forms amyloid plaques. An investigation of the factors involved in this transformation of apo A-1 to an amyloidogenic protein will be an exciting task for an interested student! Another important project is
isolation and characterisation of apo A-1 from blood. The methods will be various protein techniques like ultra centrifugation, gel chromatography, HPLC, Western blot, immunohistochemistry, electron microscopy with others.

The work will be performed in the funniest group at the Rudbeck laboratory-the amyloid group.