Cross-Linking Amyloid Forming Proteins for Improved Understanding of Early Aggregation

Student: Gram Booth

Mentor: Dr. Christa Hestekin

Institution: University of Arkansas

Title of Project: Cross-linking amyloid forming proteins for improved understanding of early aggregation

Project Summary:

Misfolding of human amylin protein leads to aggregation, or interactions of proteins into a group, which is involved in a variety of diseases including Alzheimer’s and type II diabetes. The around five million Americans that have developed Alzheimer’s disease continues to increase with the aging population. In the U.S. alone, over 29 million people had been diagnosed with diabetes by 2014, most of which representing type II. In order to properly treat these diseases, understanding of the underlying mechanism for protein aggregation has been an important topic of study. Our project focusses on the difficult to analyze early stages of aggregation. Photo-induced cross-linking of unmodified proteins (PICUP) was used to study these early, unstable stages of protein aggregation by allowing us to take “snapshots” of the protein aggregation as it progresses. PICUP allows researchers to collect data about the smaller, more toxic stages that are still soluble and therefore more maneuverable in the body. PICUP allows these early protein aggregates to be analyzed for characteristics including: size distribution, relative abundance of the different sizes, and hydrophobicity. Results from this project may allow for the creation of better models to represent aggregation in diseases such as type II diabetes and Alzheimer’s. The improved understanding of the aggregation mechanism could also lead to treatments for the reduction or inhibition of aggregation.