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Lena's journey: Achievement is every step

Russian-born researcher, grad student, mother of four breaksground with explanation of chromosome duplication, transfer
Elena Linardopoulou
Elena Linardopoulou is the lead author of a study showing that subtelomeres — the regions just before the tops of chromosomes — are more dynamic and variable than previously thought. Her study explains, for the first time, the mechanism by which these chromosomal segments duplicate and transfer. Understanding the process of DNA breakage and repair will provide clues to the causes of genetic disorders. Photo by Todd McNaught

Elena Linardopoulou has to be an early riser if she wants to stay on top of her life. After eight years of getting up at 5 a.m. to work on her doctorate in bioengineering, raise four children and become more familiar with the English language, Russian-born Linardopoulou has written a paper worthy of publication in Nature, and her work could help researchers better understand causes of genetic disorders.

Linardopoulou's findings fit in with a group of papers in the Sept. 1 issue of the journal, which features the sequencing of the chimpanzee genome. The international research organization, Chimpanzee Sequencing and Analysis Consortium, recently completed the daunting task. And while Linardopoulou's work focuses on human genetics, her findings may point scientists to early answers in further understanding of the chimp genome.

Chromosomal exchange

Hutchinson Center genomics scientist Dr. Barbara Trask, along with Linardopoulou and other team members, report that subtelomeres — the regions just before the tips of chromosomes — are much more dynamic and variable than previously thought. "The significance is how recent and how much exchange activity there is between chromosomes. Most of us think of a DNA sequence being on a given chromosome pair that you inherit, and acquiring subtle mutations to change slowly over time," Trask said. But those changes stay on the maternal or paternal copies of that chromosome. In subtelomeric regions, a sequence moves from one chromosome to another and maybe even moves back again, shuffling the contents. "So you end up with a patchwork of pieces that are not on a single pair of chromosomes, but on multiple chromosomes," she said.

Since humans and chimpanzees diverged more than 6 million years ago, the transfers and duplications have been happening at a remarkable rate. Despite the fact that the subtelomeric regions represent only one one-thousandth of the whole genomic landscape, about half of the interchromosomal duplications happen there, which means the area is very active. "We never realized before how much of the sequence has been generated after we diverged from chimpanzees and how much variation we have," Linardopoulou said. "Based on our findings we suggest an existence of a general cycle between DNA segment variation and genomic rearrangements."

Linardopoulou's work in the Trask lab also supports the idea that the difference in gene content between humans and chimpanzees could be much greater than previously understood. Using a technique to fluorescently tag specific DNA sequences, called fluorescence in situ hybridization, or FISH, researchers in the Trask lab are able to quickly scan subtelomeres for similar sequences. Despite the fact that not much is known about chimp subtelomeres, researchers could compare the locations and numbers of copies within the chimpanzee and human genomes to assess how much change had occurred. Linardopoulou could also look at the human sequences on different chromosomes, compare them, and infer when duplications happened. "If a sequence duplicated just yesterday, the copies will be identical. However, as time passes, each copy accumulates mutations, and since we know the speed with which mutations accumulate, we can calculate how far back the copies are related," Linardopoulou said.

Bad DNA breaks

This is the first time the mechanism by which these chromosomal segments duplicate and transfer has been explained. When DNA breaks, it must be repaired. Linardopoulou's paper indicates that most of the repairs that create the subtelomeric patchworks happen by joining the end of one broken DNA molecule with another DNA break, even if it doesn't contain the same sequences. By understanding this process, researchers can have a better understanding of the causes of genetic disorders.

But perhaps what's most remarkable of all of the findings is the fact that Linardopoulou was the prime mover of the study, Trask said. Linardopoulou grew up in a small town outside of Moscow. After earning her undergraduate and master's degrees in Moscow, she left Russia and eventually made her way, via Greece, to Seattle with her daughter to start her doctorate work at the University of Washington (UW). "What's so amazing is that when Lena first came to my lab, her English was not great," Trask said. "She had a hard time explaining things and organizing her thoughts." Now, Linardopoulou has gained the confidence and the ability to easily explain complex material.

"She's very intense, and she gets very excited about DNA sequence analysis and has done an amazing job of keeping an enormous amount of detailed information in her head," said Trask, who was once concerned that Linardopoulou, who speaks four languages, would get frustrated and leave graduate school, taking all of that knowledge with her.

Life lessons

But Linardopoulou said she can't imagine life without her work. "Working here in the lab is one of the best parts of my day," she said. "It's an amazing time now to be working in this field when so much information comes in and so many tools are available to analyze it from all possible angles." Being able to think creatively about the research is a big part of the appeal for her. "I think that's why it's so interesting. It's a puzzle and it has very interesting consequences."

Figuring out all these puzzles and raising a family doesn't leave much room for spare time — or boredom — Linardopoulou said. Her youngest is a year and a half old, and her oldest daughter is taking college courses in England. At 41, Linardopoulou said she has learned some valuable lessons in the wake of the difficulties she has faced. "Accepting life as it comes is very important, trying to see all the good things that are happening as much as you can, and pass by the bad things and hope they won't be there tomorrow." Linardopoulou credits her husband, also a graduate student at the UW, for being a tremendous help to her during the long days and nights of research in the lab. "You need support, that's very important," she said.

Linardopoulou will defend her thesis in the fall and plans to continue research in the Trask lab for another year before deciding what to do next. And although the next year promises to continue at this breathtaking pace, she says, "Celebrate life because you realize that it's not endless."

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Last Modified, October 28, 2019