UConn Health Center Researcher Awarded $9.3 Million Grant for Human Genome Study

Brenton Graveley, professor of genetics and developmental biology. (Lanny Nagler for UConn Health Center)

Brenton Graveley, professor of genetics and developmental biology. (Lanny Nagler for UConn Health Center)

A prominent University of Connecticut Health Center researcher has been awarded a $9.3 million grant from the National Institutes of Health (NIH) to expand scientific understanding of the role that the human genome plays in health and disease.

The research of Brenton Graveley, professor of genetics and developmental biology, will help expand the ENCyclopedia Of DNA Elements (ENCODE), a comprehensive catalog of functional elements that control the expression of genetic information in a cell. Graveley is the lead investigator of the project that also includes scientists from the Massachusetts Institute of Technology and the University of California, San Diego.

“Most of the changes that affect disease do not lie within the parts of genes that we thought they did,” Graveley explains. Instead, they lie in regions of the genome that act as genetic “switches” that turn genes on or off in particular cells or tissues or at particular times. The ultimate goal of the immense ENCODE project is to learn how human diseases such as diabetes, lupus, and cancer can be linked to genetic changes that appear to be turned on and off within DNA by specific mechanisms.

“It turns out that the part of genes that are used to make protein make up only 1 percent of human DNA,” Graveley says. “The rest of the genome is what is clearly important for controlling genes.” In the past, researchers believed only 5 to 10 percent of a person’s DNA was being used. But researchers now realize that almost all of the DNA is used and that a large proportion of it is gene switches.

ENCODE was launched in 2003 to carry out an ambitious project to identify all functional elements of the human genome sequence. Graveley’s team will analyze human RNA transcripts to identify protein binding sites within the RNA and investigate their function. This work represents ENCODE’s first production scale effort to map protein binding sites in RNA.

Graveley’s research, which began with the study of the DNA and RNA of fruit flies and has extended to humans, builds upon his years of experience and has a goal of making a direct impact on human health. “The idea is to identify every place in the entire genome where proteins bind to either DNA, or in our case RNA,” Graveley says. “We hope to gain insight into proteins that have never before been studied. By learning how they work, we hope to better understand why a person develops a particular disease, and from there how to cure it.”

State and federal grant funding in the millions, collaborations with premier institutions such as MIT and UCSD, and the commitment of Maine-based Jackson Laboratory to build a $1.1 billion research facility on the Health Center’s campus are combining to put Connecticut squarely on the map as a hub of genomics and personalized medicine.

The benefits of this recognition are both economic and medical. The rising stature of UConn research and the Jackson Labs collaboration is expected to bring thousands of jobs and more high-profile experts to Connecticut. But the research also promises huge strides toward conquering disease by unlocking the mysteries of how the human genome works.

The goal one day is for genome mapping to become so accurate and inexpensive that labs can perform a complete analysis of each person’s genome, and from there doctors can precisely diagnose a disease and understand the best way to treat it.

All of the data generated by the ENCODE project will be deposited into public databases as soon as they are experimentally verified. Free and rapid access to these data will enable researchers around the world to pose new questions and gain new insights into how the human genome functions.

Graveley, who joined the UConn Health Center in 1999 and is respected throughout the world for his research, is the lead investigator for the study being funded by the highly competitive NIH grant. The other principal investigators are Christopher Burge from MIT, and Xiang-Dong Fu and Eugene Yeo from the University of California, San Diego. The four researchers work in various aspects of RNA biology.

Graveley was a co-investigator in previous RNA research studies. “He has gone from co-investigator to lead investigator, and it’s a feather in UConn’s cap to have someone here with this kind of stature,” says Marc Lalande, professor and chairman of the Health Center’s Department of Genetics and Developmental Biology. “He has had great success, and I am especially proud that he’s in my department.”

The ENCODE grant is an important step for UConn as it prepares to team up with Jackson Labs, experts in genomic medicine. “We are poised to really bring this collaboration together and have a synergy between the two institutions,” Lalande says. “Brent Graveley is one example of the genomics excellence we have here. There is a lot of exciting work to be done in this area. The grant for this research is just the tip of the iceberg.”

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