Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) will receive $10 million over the next 6 years to find the genetic causes of congenital heart disease. Congenital heart disease affects 1 percent of all children and often leads to death or long-term illness. The team of investigators, led by Benoit Bruneau, PhD, will focus on the gene networks that underlie the disease and the regulatory factors that turn on and off genes related to congenital heart defects (CHDs). GICD was one of four national centers awarded this highly competitive grant to address CHD at a genome-wide level.
"We know that specific genes have to be turned on and off during a relatively narrow developmental window to correctly build a human heart," said Dr. Bruneau, who is the William H.Younger, Jr. Investigator at Gladstone. "But so far we only understand how a handful of genes change during heart formation. Our study will look at all of the 25,000 genes in the genome to get a full picture of how the entire system is regulated. Understanding the all of the regulatory networks that control heart development will have important implications for preventing and curing congenital heart disease."
According to Bruneau, the research team will use cutting-edge genome-mapping techniques to identify and define the function of transcription factors with known roles cardiac development and human disease, and so-called epigenetic regulators, the factors that open up chromosomes to allow the transcription factors to reach their targets.
Transcription factors are the "master regulators" of a cell, acting to turn on or off other genes; they function by directly interacting with DNA, but it isn't known how they function in concert with epigenetic regulators.