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2019 Alzheimer's Association Research Fellowship (AARF)

Disruption of 3D-genome structure in Alzheimer’s Disease

How is the organization of genes in nerve cells affected in Alzheimer’s disease?
 

Vishnu Dileep, Ph.D.
Massachusetts Institute of Technology
Cambridge, MA - United States



Background

All of the genes in a cell are programmed in the DNA, a long chain of molecules that is folded in a very specific way. The folding of DNA chains affects which genes in the chain are turned on or off, and the folding pattern changes depending on which genes are needed at any given time. In neurodegenerative diseases like Alzheimer’s disease, researchers have found “breaks” in the DNA chain that disrupt the normal folding pattern and that in turn affect which genes are turned on and off.
 

Research Plan

Dr. Vishnu Dileep proposes that breaks in the DNA chain inside nerve cells in Alzheimer’s brain can cause misfolding of the chain that impacts genes important for nerve cell function. To conduct their study, the researchers will compare the folding patterns of DNA in nerve cells from various types of genetically engineered Alzheimer’s-like mice and from people with Alzheimer’s disease. Dr. Dileep will create three-dimensional (3D) distribution of genes in the entire DNA chain to determine which genes are affected by the misfolding. The researchers will also test whether the breaks in the DNA chain are directly responsible for the misfolding by exposing nerve cells— taken from individuals with Alzheimer’s —to various chemicals that can either cause or prevent these breaks.
 

Impact

This study would be the first to lay out how the folding of DNA in nerve cells is impacted in Alzheimer’s disease, and which genes are altered because of DNA misfolding. If successful, the results may also lead to new therapies to reduce breaks in the DNA chain in Alzheimer’s disease.
 

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