Einstein Researcher Receives NIH Grant to Develop Technologies for Exploring Epigenetic Regulation of the Human Genome
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A researcher at the Albert Einstein College of Medicine has been awarded a $1.5 million, three-year technology development grant from the National Human Genome Research Institute (NHGRI) of the National Institutes of Health.
Dr. John Greally, associate professor of medicine and of molecular genetics at Einstein, received one of six technology development grants awarded by the NHGRI as part of its ENCyclopedia Of DNA Elements (ENCODE) project.
Dr. Greally studies epigenetics, an emerging field that involves changes in gene expression that do not result from changes in DNA sequence. These epigenetic changes can be passed on from one cell generation to the next. The epigenetic regulation of genes—turning them on and off—is crucially important: Glitches in epigenetic control mechanisms, for example, have been found in every type of cancer that researchers have examined to date.
During his three-year project, Dr. Greally plans to develop new means of identifying patterns of epigenetic regulators in the human genome, gaining insights into how these epigenetic mechanisms control genes. Dr. Greally will team with Brad Bernstein, M.D., of Massachusetts General Hospital and Andi Gnirke, Ph.D., of Boston’s Broad Institute to develop these new assays that are based on the use of high-throughput sequencing.
“The high-throughput sequencer will allow us to generate billions of base pairs of DNA sequence information in each experiment, allowing us to study the epigenome at a level of resolution that has never previously been possible,” said Dr. Greally, who is principal investigator for the team. “We’ll be able to view things in greater detail and with greater accuracy than ever before.”
The researchers will be developing high-throughput methods to analyze and map the two principal epigenetic control mechanisms: methylation of cytosine (one of four nucleic acids found in DNA) and modifications of histones (proteins that help to package DNA into chromosomes). The methylation (addition of a methyl group, CH3) of cytosine switches genes off, which can be associated with certain diseases such as cancer. The second key epigenetic mechanism—modifying histone proteins—also helps to control whether or not a gene is expressed.
“The technology we’re using will allow us to identify the genetic mutations responsible for the epigenetic dysregulation that results in human disease,” added Dr. Greally. “In doing so, we can then develop potential targets for treatment.”
