One of the challenges of learning more about the human brain is understanding how it functions in the first place. Ours is one of the most elegant and complex in the animal kingdom, and unlocking its secrets could lead to untold discoveries about the human nervous system, memory, and learning.

A new grant awarded by the National Institutes of Health to Biocomplexity Institute of Virginia Tech’s David Xie will help researchers understand how transcription factors regulate certain key processes through DNA methylation within the brain. With this information, researchers will understand more about long-term memory and possibly even how to regain or retrain functions that some patients have lost.

Think of the brain as a smartphone with a basic operating system that everyone receives at birth. After a certain amount of time and development, everyone’s phone will be different — loaded with different apps, photos, music, and games. But how and when did they become different? How do the environment and other factors shape each individual version of the phone?

“It’s very much the same with the brain — some genes are activated and some not. Why? That’s what we hope to find out,” Xie said.

As researchers have found in previous studies, certain abilities, like learning a new language, are more easily available at certain developmental stages. It is far easier for a toddler to become bilingual than a full-grown adult, for example. These windows open and close at certain stages of life, but researchers are not entirely sure why.

“At key points, your brain is not programmed to receive certain kinds of information,” Xie notes. “When is the right time for certain brain functions to occur? We don’t understand why the ability window is open at some moments and not others. What if we could retrain the brain to regain function?”

However, some of the clues may be held in the “brain methylome,” an umbrella term for the genes in the brain controlled or altered by DNA methylation, which operates like a series of often-conjoined switches that either activate or suppress gene function. Understanding DNA methylation is key to the budding field of epigenetics, which focuses on the inheritance of the methylome. Since DNA methylation is important in the maturation of neurons in the brain, it’s important to know how it occurs and how it affects development of synaptic connections as the brain develops after birth.

Xie’s lab has developed strategies to explore how transcription factors involved in DNA methylation help open the window to learning. The techniques used by Xie’s team were developed in his laboratory after years of research in pediatric neurology and can be applied to other parts and systems of the body, such as immunity.

“We know how brain cells code differently, but now we need to know how transcription factors turn on the switch,” Xie said.

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