Biochemical and structural studies of amyloid enhancing factor

• Applicant: Professor Dr. Marcus Fändrich
• Subject Area: Biochemistry
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260764931

Systemic AA amyloidosis is a protein misfolding disease that affects humans, mammals and birds. The disease is caused by the formation and deposition of AA amyloid fibrils in spleen, kidneys and liver. While AA amyloid fibrils are composed of fragments of the serum amyloid A (SAA) 1.1 protein, there is long-standing evidence that injection of crude spleen extracts, termed amyloid enhancing factor (AEF), into appropriate recipients accelerates amyloid deposition. As these partially enriched spleen extracts were found to often comprise at least small levels of AA fibrils, a prion-like mechanism of propagation was suggested, although the active species was never fully purified. Using modern biochemical methods and a cell model of SAA fibril formation we will isolate AEF from its native source to analyze its molecular properties with a battery of biophysical methodologies. Resulting hypotheses concerning the constitutional and conformational composition can then the tested by in vitro reconstitution. As spreading is an important feature of conformational diseases in general, expected data could be of broad scientific and public interest.

• DFG Programme: Research Grants