Discovering How Cells Get the Right Chromosomes
Sue Biggins, Director of Basic Sciences Division
As a newly minted researcher, Dr. Sue Biggins chose Fred Hutchinson Cancer Center because of what it isn’t: It isn’t about playing it safe or working alone. It isn’t about empire building. It’s not full of policies and politics to trip over. It’s all about having the freedom, she said, to do the best, most unconventional science possible.
“Definitely more home runs are hit here because there’s an unspoken expectation that you should do something big, stuff that’s really going to be a game-changer,” said Biggins, who directs the Basic Sciences Division. “Good fundamental science is inherently risky.”
That risk is allayed by a division-wide spirit of collegiality in which colleagues champion each other’s success. In her new role, Biggins aims to maintain this spirit and continue fostering it in the next generation of Basic scientists.
Before she became a researcher, Biggins thought the mechanics of cell division were completely understood. It didn’t take her long to figure out that many questions remained, and she sought to answer some of them. In the Hutch’s Basic Sciences Division, she made an important contribution to the study of cell division by figuring out how specialized “cellular machines” known as kinetochores allow cells to separate and distribute their chromosomes accurately.
For decades, researchers had tried and failed to isolate or assemble whole, functioning kinetochores to better understand how they help chromosomes separate and end up in the right daughter cell. If this goes awry, entire chromosomes are gained or lost, a hallmark of most cancer tumors, hereditary birth defects and miscarriages.
Biggins’ team, stepping away from genetic methods and borrowing from biochemists’ playbook, succeeded in separating the kinetochores from dividing yeast cells and studying them in test tubes for the first time. During cell division, kinetochores act like handles on chromosomes and are under tremendous pressure as fibers pull on these handles to move the chromosomes within the dividing cell. If chromosomes fall off in the midst of this process, they don’t end up in the daughter cell. Biggins and colleagues found that the harder the kinetochores are pulled, the harder they attach, like a finger-trap toy. This counterintuitive characteristic explains why the process works correctly so often.
This advance also made further findings possible, including the first close-up pictures of an assembled kinetochore, using a technique called electron microscopy, or EM. The structure is now included in fundamental biology classes taught to college students.
“Definitely more home runs are hit here because there’s an unspoken expectation that you should do something big, stuff that’s really going to be a game-changer."
What’s true in yeast is also true in human cells. Because kinetochores play such an important role in chromosome segregation, knowing how they work turns them into very large therapeutic targets. If research leads to drugs that disrupt kinetochores from doing their job in unhealthy cells, they would be unable to divide and propagate at all, stopping a disease such as cancer.
Biggins’ kinetochore breakthrough came with help from Basic Sciences colleague Dr. Toshio Tsukiyama, who took time to teach her biochemistry methods. “I had absolutely no experience with biochemistry, but it was clear to me that for the field to progress, someone had to figure out how to pull the kinetochore out of the cell,” she said, noting that Tsukiyama’s assistance is commonplace at the Hutch, and in particular the Basic Sciences Division, where collegiality is prized.
Division director is merely Biggins’ latest leadership role. She has served on numerous national scientific committees and review groups including the Next Generation of Science committee of the National Academy of Science, which aims to improve science for early stage U.S. investigators. She has also been actively involved in editing for journals including the Proceedings of the National Academy of Sciences. She is currently a member of the Coalition of Life Sciences, a national alliance that fosters policies to promote research in the US.
She is an elected member or fellow of several science academies, including the American Academy of Arts and Sciences and the National Academy of Sciences. Her awards include the 2015 Edward Novitski Prize from the Genetics Society of America and the 2013 National Academy of Sciences Molecular Biology Award. In 2015 she became a Howard Hughes Medical Institute Investigator.
As director of the Basic Sciences Division, she continues to encourage the collegial ethos to which she credits her own success.
“I’m surrounded by unselfish colleagues willing to make other labs as successful as their own,” said Biggins.
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