A multisystemic study of the Serum Amyloid A protein and Serum Amyloidosis disease

Systemic amyloidosis is a name for a group of diseases caused by protein misfolding. Serum amyloid A1 (SAA1) is the precursor protein of the amyloid fibrils present in systemic AA amyloidosis, a disease affecting the human spleen, kidney and liver and may lead to a fatal outcome. This protein is secreted as a part of the acute phase response to bacterial inflammation, and its primary role is to bind HDL in the serum, but to this day not much is known about its other roles nor the cause of misfolding and aggregation. No disease-modifying therapy is so far available to directly control the aggregation process in this disease and treatment is primarily based on reducing the blood SAA1 levels.

In this study, we aim to use a multisystemic approach to study the disease and its causes by understanding the purposes of the SAA secretion and its structure. While many of biophysical analyses of the mechanism underlying amyloid formation are conducted with pure polypeptide chains in simple chemical buffers, we aim to establish a cell culture model that will provide a native cellular environment, which is much more complex, for testing of our rationally designed compound inhibitors as well as compound libraries. In addition, we will focus on developing a novel antibacterial treatment in order to prevent the underlying cause of the upregulation of this protein - inflammation.