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Location

Disque Hall Room 919, 32 South 32nd Street, Philadelphia, PA 19104

Audience

  • Current Students
  • Faculty

Physics Colloquium: Molecular Structural Basis for Amyloid Formation, in Vitro and in Vivo

Thursday, March 6, 2014

3:30 PM-4:30 PM

Robert Tycko, PhD, senior investigator, Laboratory of Chemical Physics, National Institutes of Health

 

Numerous peptides and proteins are capable of forming amyloid fibrils, which are self-assembled filaments containing ribbon-like ß-sheets, typically 5-10 nm in diameter and microns in length. In amyloid diseases such as Alzheimer's disease (AD) and type 2 diabetes, amyloid formation by particular peptides (the ß-amyloid or Aß peptide in AD, the islet amyloid polypeptide in type 2 diabetes) causes or contributes to cell death in the affected tissue. Detailed molecular structural information is a requirement for understanding why peptides and proteins form amyloid fibrils, can contribute to our understanding of pathogenic mechanisms, and can guide drug development. The inherently noncrystalline, insoluble nature of amyloid fibrils makes such information difficult to obtain.

Fortunately, amyloid fibrils are ideally suited for solid state NMR methods, including advanced methods developed in our lab. In this lecture, I will review work, begun in 1998, in which we have investigated structures of Aß and other fibrils, providing the first experimentally-based insights into varous principles that govern amyloid formation, as well as the first detailed molecular structural models. Of central importance is the finding that amyloid structures are not determined uniquely by amino acid sequences, i.e., amyloid fibrils are polymorphic at the molecular level. Thus, our current work focuses on determining the molecular structures of Aß fibril polymorphs that develop in brain tissue of AD patients, and on examining possible correlations between fibril structure and the clinical or neuropathologic aspects of AD.

Contact Information

Professor Frank Ferrone
ferronfa@drexel.edu