Bowler, Jeannette
Jeannette is in the Biochemistry, Biophysics, and Structural Biology home area of the MBIDP. She joined the training program in 2015. Her research mentor is Dr. David Eisenberg. She received a B.S. degree in 2014 from San Francisco State University.
Mentor: Dr. David Eisenberg
Amyloid proteins are associated with a variety of diseases including Alzheimer’s, Parkinson’s, and type II diabetes. These proteins can form oligomers and fibrils, and eventually fibrous aggregates seen in the histology of affected tissue. Alpha-synuclein (α-syn), the neuronal protein implicated in Parkinson’s disease, is the primary component of Lewy bodies, protein aggregates found in the brain tissue of Parkinson’s disease patients. Althoughinsoluble aggregates are the hallmark of the disease, recent evidence indicates that the oligomeric species is likely to be the pathogenic form. The structural basis for oligomer and fibril formation, as well as the mechanism of toxicity, is unclear. A deeper understanding of this mechanism would be invaluable for the development of treatments for Parkinson’s disease and other synucleinopathies.
Previous studies have shown that the interaction of α-syn with lipid membranes accelerates β-sheet rich fibril formation. The core of this fibril is formed by a segment of 11 hydrophobic amino acids, termed the NACore, which is necessary for aggregation and cytotoxicity. I am interested in characterizing the interaction of the NACore with lipid membranes, as well as understanding the mechanism of oligomer formation and cytotoxicity of α-syn. I am currently working towards determining the structure of the NACore in complex with lipids, using x-ray crystallography and other biophysical methods. Characterizing this interaction would be a major step forward in understanding the molecular mechanisms involved in Parkinson’s disease progression, including the transition of α-syn from the monomeric to oligomeric form.
