Award-winning geneticist Leonid Kruglyak, PhD, didn't start his career in a biology lab. He trained in theoretical physics and honed computational skills that served him well when he switched to human genetics research in 1993.
"The Human Genome Project was just ramping up, and it was really interesting stuff," says Dr. Kruglyak, professor of human genetics and biological chemistry in the David Geffen School of Medicine at UCLA and investigator in the Howard Hughes Medical Institute. "It was clear the field would need more mathematical and quantitative expertise, and I thought I could make a real contribution."
Kruglyak was right; in the past 20 years, his work has been cited more than 40,000 times in scientific literature. He personally has received numerous awards as well. Most recently, the American Society of Human Genetics honored him with the 2015 Curt Stern Award for outstanding scientific achievements over the past decade.
Receiving this award has been gratifying and humbling for Dr. Kruglyak. "Scientists spend many years doing work we hope is having an impact," he explains. "But we know lots of other people are doing important work, too. Being singled out by my colleagues means a lot to me."
Here's why Dr. Kruglyak is considered a pioneer in human genetics, and what's next for this award-winning researcher.
From providing answers to asking questions
Dr. Kruglyak has devoted his career to understanding how changes in genes lead to differences between individuals, and how genetic information ultimately passes through generations. His earliest achievements weren't about asking those questions, but about giving other scientists the tools to answer them.
In the mid-1990s, he developed algorithms for GENEHUNTER, a computer program that allowed geneticists to analyze complex data sets from human families that carry genetic diseases. He published several key papers on this concept, including a controversial prediction about the number of genetic markers required for genome-wide association studies in humans.
"My number was much higher than people thought was necessary or practical at the time," Dr. Kruglyak says. "Some insisted I was wrong. Others thought that even if I was right, putting such a daunting number out there might slow down the field. But the opposite happened. A number of practical projects sprang up. My prediction was largely validated, and the types of studies that people thought would be impossible based on that number are now routine in the field."
Although Dr. Kruglyak lists these among his proudest accomplishments, he eventually shifted focus and opened his first experimental lab at the Fred Hutchinson Cancer Research Center in Seattle. In 2002, he published the results of his groundbreaking work on gene expression (eQTL analysis).
"I originally considered myself a technology guy," Dr. Kruglyak admits. "I had the skill set to attack problems mathematically in a way that would help other geneticists who were asking scientific questions. This was really a shift in my career — from thinking about how I could help other people answer questions, to thinking about what questions I wanted to ask."
The Kruglyak Lab at UCLA
Today, Dr. Kruglyak asks questions in his laboratory at UCLA, where he's using the baker's yeast "Saccharomyces cerevisiae" and the roundworm "Caenorhabditis elegans" as models for studying complex genetic variation.
"One of the maxims in physics is to study phenomena in the simplest possible system," Dr. Kruglyak explains. "All the complex inheritance patterns we want to understand in people also take place in yeast, but its genome is 300 times smaller than the human genome, and the biology of its genes is better understood, so we can make more sense of the information."
Dr. Kruglyak's team is trying to get the most comprehensive picture possible of how genetic inheritance works, using state-of-the-art technology. "This has been a golden age in technology development, and UCLA has made significant investments in human genetics and genomics. We can do experiments today that five years ago would have been pure science fiction, and we'll be able to do even more far-out ones in the next five years," he says.
By Taylor Mallory Holland