To view an abstract, select an author from the vertical list on the left.
2014 Grants - Fowler
Large-Scale Mutagenesis to Probe ABeta Aggregation and Chaperone Interactions
Douglas McKay Fowler, Ph.D.
University of Washington
2014 New Investigator Research Grant
Abeta, also known as beta-amyloid, is a protein fragment that forms clumps known as amyloid plaques, one of the characteristic features of Alzheimer’s disease in the brain. Our understanding of how beta-amyloid behaves in the brain is limited and questions remain regarding how the amyloid plaques form and what factors may be involved in the initiation of this process.
Douglas McKay Fowler, Ph.D., and colleagues have developed a new technique for studying how beta-amyloid behaves in living cells. The researchers induce misspellings – known as mutagenesis – in the beta-amyloid, then study how each change affects the molecular properties and toxicity of the altered protein. By combining this technique with computer modeling of protein properties, the researchers can construct a comprehensive model of how the beta-amyloid protein functions and abnormally clumps into the amyloid plaques.
Dr. Fowler and colleagues have proposed to use this method to understand how beta-amyloid forms clumps – or aggregates – and then determine which types of aggregates may contribute to the brain changes associated with Alzheimer’s disease. Because beta-amyloid can bind to other proteins called chaperones, which may also be involved in the aggregation process, the researchers plan to study how mutations of beta-amyloid affect these interactions. These studies may lead to new insights into the mechanisms of beta-amyloid aggregation, and to new strategies for preventing the formation of amyloid plaques and their detrimental effects in Alzheimer’s disease.