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Genomics revolution Cutting-edge research could lead to new breakthroughs By Kathleen Haughney Professor of Biological Science David Gilbert and his research team are examining how DNA replicates and whether that has a particular influence on cells that are found in pediatric leukemia patients. I n a lab at Florida State University, Professor of Biological Science David Gilbert is trying to solve a serious problem. He’s trying to figure out the causes of pediatric leukemia. The answer may lie in the cell’s DNA. With this particular experiment, Gilbert and his research team are examining how DNA replicates and whether that has a particular influence on cells that are found in pediatric leukemia patients. “We’ll look for clusters or patterns where the DNA replication did not work properly and then see how that matches up with cells of leukemia patients and cells of healthy patients,” Gilbert said. Gilbert is just one of many scientists at Florida State who are delving into the complicated area of genomics with the hope that a better understanding of our genetic material will lead to advances in diseases like diabetes or leukemia. It’s an enormous area of research that combines in-depth knowledge of biological systems with complex “big data” analysis. “I was in computer science in the 1970s and 1980s when it was the hot new thing,” said computer science Professor Gary Tyson, who last year helped undergraduate researchers sequence the manatee genome. “Genomics research is exploding at a faster rate than that.” And genomics is enveloping researchers from a number of disciplines. Scientists in the FSU Department of Biological Science, the Department of Computer Science, the Department of Scientific Computing and the College of Medicine are all working on genomics in some form or another. Take Hank Bass, an associate professor of biological science. He’s a plant biologist who spends a lot of time studying maize. Why corn, you ask? Well, corn is one of the most genetically diverse plants and it dates back thousands of years, making it a model genetic organism. Through the study of maize, Bass has discovered that plants share some interesting genetic similarities with humans. Or you might look at work by Bass’ colleague in the Department of Biological Science, Professor Kimberly A. Hughes. Last year, she found that a genetic rarity in male guppies that affects their color patterns plays a role in how often they mate. This genetic rarity makes a certain group of guppies far more colorful than the traditional male guppy. And as it happens, these colorful guppies mate more often. Then there is Peter Beerli, a professor of scientific computing. He writes open-source computer programs that can handle a wealth of genetic data and enables researchers to better understand their data. Right now, genomics research is in demand, and researchers are doing everything they can to keep up. “Genomics permeates almost everything we do,” Gilbert said. One of the reasons for this is recent advances in technology. Ten years ago, it cost hundreds of thousands of dollars to fully sequence the human genome, but today, with technology breakthroughs, the cost is less than $1,000. The burgeoning area of research also recently led Florida State to open a new Center for Genomics and Personalized Medicine. The idea behind the center is to bring together the expertise of biologists, who are asking 2
Ray Stanyard the traditional big questions about plant or animal biology, and computer scientists and mathematicians who are trained to handle big data. “Just managing that information and analyzing that data is beyond a lot of our expertise,” said Bass. “We know how to ask the questions. For example, you have a new strain of corn that is drought-resistant and you want to know what the difference is in the gene content. I can ask the question, but I don’t have the computational wherewithal to answer it. A lot of these questions we have are longstanding questions, and the tools are just becoming available for us to look at them.” The whole aspect of figuring out those answers is what led Beerli, who originally trained as a biologist, to start writing computer programs. During his graduate training at the University of Zurich in the early 1990s, he studied evolutionary genetics of frogs. “I had all these questions, but I couldn’t analyze the data the way I wanted,” Beerli said. “Sometimes, scientists are interested in how a population ended up on this island or why they crossed a certain geographic boundary, like a river,” Beerli said. With genomics research, the general idea is that understanding one species might help scientists understand another species and then another. The overall effect of this type of research is wide and varied. For researchers studying the human genome, the ultimate goal is to find ways to prevent diseases such as cancer or diabetes. For plant biologists, scientists might want to find out new ways for plants to thrive in adverse conditions — knowledge that would be a huge boon for the agriculture industry. Or it’s possible that knowledge about a plant might lead to knowledge about mammals, even humans. Bass is among the researchers heavily involved in genetics research. His lab has been searching for the similarities between plants and animals in how genetic structures form and then function. crucial area of research. But there remains little knowledge of the structures overall. So Bass, a plant biologist, believed that an analysis of maize might yield more answers. The general public thinks of DNA as two connected strands known as the double helix. But scientists also discovered over the years that those strands regularly separate so they can replicate the genetic material. That material can also twist into different shapes such as a G-quadruplex. In Bass’ work, he found not only that those same structures existed but that they were suspiciously prevalent at genes associated with energy metabolism, suggesting they have a specific function. The next step is to find out exactly how the G4s affect gene functions. Bass and Assistant Professor Elizabeth Stroupe, whose lab spearheaded a separate discovery about G4 DNA, are hoping to jointly conduct the first-ever computational screen of the G-quadruplex in the near future. Beerli authored MIGRATE, a computer program that helps scientists analyze genetic data. Using MIGRATE, scientists can see where different populations of species settled and how their genes adapted or didn’t adapt to suit those areas. Most recently, Bass has examined the role of a DNA structure called a G-quadruplex or G4 DNA. G4 structures regulate genes in humans that affect cancer and cell division, making it a Peter Beerli is a professor of scientific computing who writes open-source computer programs that can handle a wealth of genetic data and lets researchers better understand that data. Ray Stanyard artsandsciences.fsu.edu S P R I N G / S U M M E R 2 0 1 5 • 3
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