Building New Tools to Study the Epigenome

Overview of Epigenome Project Design

Most people know genetics is the study of genes, and think of genes as the blueprint for living things. But it’s not quite that simple.

Inside of living cells, genes are made up of DNA, and the DNA is formed into strands in the shape of a double helix. In higher organisms, like humans, the double helix is wrapped around proteins, which help pack the DNA into tight bundles and can help regulate whether a gene is expressed (turned “on” or “off”).

Professor Albert Keung
Professor Albert Keung

When people talk about the “epigenome,” they’re referring to the collection of proteins and chemical modifications that are bound to either the DNA itself or to the proteins that DNA is wrapped around inside a cell. These proteins and chemical modifications play a key role in determining the extent to which a gene is expressed.

Changes in the epigenome can lead to a wide variety of health problems – from cancers to autoimmune disorders. But not only is there a lot we still don’t know about the epigenome, we don’t even have the tools to find out.

At present, researchers who study the epigenome have to harvest the DNA and related epigenetic material from hundreds of thousands of cells to get one sample. The sample is then subjected to biochemical analysis to determine what epigenetic material is present.

Professor Bala Rao
Professor Bala Rao

Researchers can learn a lot from this work, such as identifying differences in the epigenome between healthy and diseased cells. But it has limits.

For example, there’s currently no way to monitor changes to the epigenome in living cells. And there’s no way to alter many properties of the epigenome in a living cell – which could help determine the precise role that a specific protein or chemical modification plays in regulating DNA expression.

CBE professors Albert Keung (principal investigator), Bala Rao (co-principal investigator), and their colleague professor Caroline Laplante (co-principal investigator) in the Department of Molecular Biomedical Sciences are working on that. The team has received a 4-year, $2 million grant, “Ascribing function to chromatin with coordinated live-cell epigenomic sensors and scalpels,” from the National Science Foundation to develop molecular-scale tools that can monitor and/or modify the epigenome.

The resulting tools could advance the entire field of epigenetics.

“The early versions of the molecular tools we have built have offered a glimpse into the previously invisible nanoscale universe of the epigenome,” Keung says. “It’s exciting not only to make tools allowing us to peer into this unknown part of our own cells, but to anticipate its broad potential benefit to human health.”

As part of the project, underrepresented student groups from local high school and undergraduate institutions will be directly involved in the research activities supporting the scientific aims of the project, with the ultimate goal of informing, inspiring, and mentoring students to pursue successful careers in Engineering or Engineering Research.

Congratulations to professors Keung, Rao, and Laplante for your exceptional success in obtaining this funding!

The original version of this article was written by Matt Shipman, Research Lead in University Communications at NC State.