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Phil Sahm

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Jan 19, 2012 1:08 PM

(SALT LAKE CITY)—At the University of Utah, creativity has played a major role in countless discoveries—from the invention of the first implantable artificial heart to the development of gene targeting—and it is a cornerstone in the school’s research mission. The U of U’s rich history of encouraging and producing creative researchers has been recognized again through biochemistry professor Dana Carroll, Ph.D.
Carroll has been chosen for the 2012 Novitski Prize, an award from the Genetics Society of America (GSA) that recognizes “extraordinary creativity and intellectual ingenuity in solving significant problems.” He is being honored for developing a method that improves the efficiency of gene targeting, a technique pioneered at the University that revolutionized the study of mammalian biology and earned U of U human geneticist Mario R. Capecchi, Ph.D., a share in the 2007 Nobel Prize in physiology or medicine.

Carroll is one of five national scientists to receive GSA distinguished service awards this year, according to Philip Hieter, Ph.D., president of the group. “The individuals honored this year exemplify the seminal contributions that genetics makes to our fundamental understanding of living systems, helping point the way toward such applications a developing new treatments for human disease and increasing the yields of agricultural crops,” Hieter says.”We are delighted to honor these geneticists who have added so much not only to our field, but to society as a whole.”

Carroll, who in 2009 stepped down as Department of Biochemistry chairman after 24 years in the position, began studying proteins called zinc finger nucleases (ZFN) in the mid-1990s. ZFNs had just been developed by a Johns Hopkins University researcher, and Carroll realized their potential to make gene targeting much more efficient.  His work allows researchers to introduce engineered changes in genes of interest into living experimental organisms for the first time. The Novitisky award comes as a bit of a surprise to him.

“To me and the people in my lab at the time, investigating ZFNs as tools for genome engineering seemed like a pretty obvious path to try,” he says. “There was evidence that if you cou

Gene targeting allows researchers to manipulate gene sequences and produce mutations in virtually any gene. By doing this, they can study the functions of individual genes and create animal models to study countless human diseases. Carroll’s insight, which came in 1996, was that ZFNs could be used to break DNA at specific points in a sequence, exponentially increasing the success rate of gene targeting. “In the original method of gene targeting, the correct gene is altered about one in a million times,” he says. “Using ZFNs, researchers have achieved success rates as high as 10 percent or better, and in some cases up to 50 percent. We had no idea it would be this effective.”

Carroll’s discovery has many potential uses in research and medicine. Currently, a small clinical trial is under way at the University of Pennsylvania to see if using ZFNs can help protect the body from HIV. The goal of this trial is to eliminate a protein called CCR5 that HIV depends on to infect immune system cells.
Creativity is critical in scientific research, Carroll believes, but he says it rarely involves a brilliant idea coming from thin air.
“Most often breakthroughs involve the coming together of threads from several different research areas, and this was true of our development of ZFNs as tools for genome engineering,” he says. Unfortunately, the current grant review process discourages creativity, according to Carroll. “There is a strong tendency for review panels to favor projects that are guaranteed to succeed, rather than those that are innovative. Also, federal funding is declining in an era when we have the most powerful tools we have ever possessed to learn how the world works and to improve the human condition.”