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Elucidating the Driving Forces from Tau Molecules to Droplet
- Lin, Yanxian
- Advisor(s): Han, Songi
Abstract
Tau protein binds and stabilizes microtubules in the neurons of human brain. Its aggregation into amyloid fibrils is a hallmark of Alzheimer’s disease and associated with many other neurodegenerative diseases. Revealing its aggregation mechanism is key to understanding the disease progress and developing therapies. Tau is recently found by us and others to form droplet, a condense, fluidic and dynamic structure resulting from liquid-liquid phase separation of proteins, RNA and other molecules. Droplet has been shown to promote amyloid aggregation of several other neurodegenerative disease-associated proteins including FUS and hnRNPA1. In the case of tau droplet, however, its principles and its relationship with tau aggregation are still unclear. This dissertation will guide you through a tour to build physical models that explain the driving forces of tau forming droplets, and to use these models to inform our new understandings of tau aggregation.
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