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2015 Grants - Goldsmith
Exploring Tau Behavior in a Microfluidic Trap
Randall Goldsmith, Ph.D.
University of Wisconsin-Madison
2015 New Investigator Research Grant
Can molecular movies help reveal how the tau protein forms tangles in the brains of people with Alzheimer’s disease?
In healthy nerve cells the tau protein helps maintain cell structure and transport nutrients. However, in the brains of individuals with Alzheimer’s disease, tau proteins become abnormal and clump together forming tau tangles, one of the characteristic features of the disease. Tau tangles can be toxic to nerve cells and may contribute to nerve cell death in Alzheimer’s disease.
Randall Goldsmith, Ph.D., and colleagues are focused on understanding how tau tangles form in Alzheimer’s disease. They plan to use cutting-edge technology to produce movies of individual tau proteins, documenting how they clump together. The researchers will use an instrument known as a microfluidic device that contains a molecular trap which can constrain a single tau protein. This key feature allows the researchers to isolate and image one tau protein for an extended amount of time. The researchers propose that molecular movies of single tau proteins will allow them to identify short-lived or transient forms of tau that may be toxic or trigger clumping. Additionally, Dr. Goldsmith’s team will use these movies to characterize how the tau protein responds to chemicals that are known to cause protein clumping.
The studies proposed by Dr. Goldsmith and colleagues will improve our understanding of how tau tangles form, and may be a key first step toward developing new drugs to slow or stop Alzheimer’s disease progression.