Frank P. Shewmaker, Ph.D.

Profile

• B.S., Biochemistry, Auburn University
• Ph.D., Biochemistry, Tulane University
• Post-Doctoral Training, National Institutes of Health

Amyloid is a highly-ordered filamentous protein aggregate that is notorious for its association with terrible human disorders such as Parkinson's and Alzheimer's diseases. The formation of amyloid is generally regarded as a misfolding event in which proteins that are normally soluble accumulate into fibrous structures. The determinants of amyloid formation and toxicity are largely unknown, and determining the atomic-level structure of amyloid is challenging because it is not amenable to the conventional structural techniques of x-ray crystallography and solution NMR. Much of the focus of our laboratory is on fundamental issues concerning amyloid formation, structure and toxicity.

Prions

Prions (infectious proteins) of the yeast Saccharomyces cerevisiae represent a special case of amyloid. While most amyloids are not considered infectious, many yeast prions are based on a self-propagating amyloid that is passed between cells during mating or from mother to daughter cells during replication. Because yeast prions are not infectious to people, they offer an easy and safe way to study the fundamentals of amyloid propagation and transmission. Also, the yeast prions are an excellent example of an epigenetic phenomenon; in this case, heritable information is structurally encoded in cytoplasmic proteins instead of within the sequence of DNA. Our laboratory is pursuing issues of prion structure, initiation and propagation.

Electron micrographs of various amyloids: