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Can we observe changes to the tau protein in live brain cells?
Yongku Cho, Ph.D.
University of Connecticut
Storrs, CT - United States
Background
The brain cell’s energy and nutrient transport system is organized in parallel strands like railroad tracks. These tracks allow nutrients to travel across the cell, delivering key materials to the cells, providing them with energy and keeping them healthy. The tau protein helps keep these tracks straight. However, in Alzheimer’s and other brain diseases like frontotemporal dementia and Pick’s disease the shape of tau protein becomes modified and this could contribute to tau tangles (a hallmark of these diseases) and subsequent nerve cell damage. Researchers are trying to understand the modifications that the tau protein undergoes over time, in the brain and how they may impact tau’s behavior. However, studies show that these changes to the tau protein can be challenging to detect in living brain cells, because the tau protein accumulates inside them. Dr. Yongku Cho and colleagues will develop new tools to detect modified tau in live nerve cells in the brain.
Research Plan
Bringing a unique expertise in chemistry, Dr. Cho’s team will create a protein that attaches to modified tau (tau that was modified at a specific location, known to cause tangles). Dr. Cho’s team will develop and test the new protein using genetically engineered Alzheimer’s-like mouse brain cells. The protein will be able to enter the cells to help researchers observe modified tau inside living cells.
The protein will contain a label, similar to a dye, that can be seen under specialized microscopes. Dr. Cho’s team will control the protein’s levels inside the cell by adding chemicals or exposing the cells to “light” that destroys the label, but does not harm the cells. Dr. Cho believes that this technique will overcome some past hurdles and allow the researchers to measure modified tau in the brain cells.
Dr. Cho’s team will also apply a new method for measuring the intensity of the protein labels once attached to modified tau. This will help the researchers to determine whether or not the new protein label has specifically attached to the correct form of modified tau. Dr. Cho believes that a direct visualization of the attached protein label to the modified tau will enable them to better understand its role in contributing to brain changes observed in Alzheimer’s and other brain diseases.
Impact
Tools developed in this study could have widespread benefit for Alzheimer’s research. If successful, Dr. Cho’s novel protein label may enable direct observation of modified tau inside living brain cells and could potentially deliver new insights about observing other protein changes in live cells. By visualizing tau in living cells, researchers can study what happens as disease changes initiate and progress in the brain. It also gives a tool for measuring the impact of potential drugs as they are being developed.
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