I. Chromosome Segregation
II. Investigating Kinetochore Function
Part I: Chromosome Segregation
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Proper chromosome segregation during cell division is critical to ensure that daughter cells inherit the correct number of chromosomes. Microtubules emanating from the spindle poles pull on sister chromatids to move one chromosome to each pole. The kinetochore, a protein complex on the chromosome, is key to regulating chromosome segregation. Kinetochores form attachments to microtubule ends (no easy feat since microtubules are constantly growing and shrinking), they sense tension to ensure that sister chromatids are connected to microtubules from opposite poles, and they signal the cell to stop cell division if attachment is not correct. Biggins gives an excellent overview of kinetochore structure and its critical functions in chromosome segregation.
When Biggins began working on kinetochores, the experiments that she could do were limited by the lack of a method to purify intact kinetochores. In Part 2 of her talk, Biggins explains how her lab purified kinetochores from yeast (for the first time ever!). They showed that the purified protein complex functioned in the same manner in vitro as endogenous kinetochores. Using electron microscopy and other techniques, Biggins and her collaborators were able to visualize the structure of the kinetochore-microtubule attachment and demonstrate, surprisingly, that tension directly stabilizes the attachment.
Dr. Sue Biggins studied biology as an undergraduate at Stanford University and initially thought she would apply to medical school after receiving her degree. However, after a summer working in a research lab, she changed her mind and decided to apply to graduate school. Biggins received her PhD in molecular biology from Princeton and was a post-doctoral fellow with Andrew Murray at the University of California, San Francisco.
Currently, Biggins is a Principal Investigator in the Division of Basic Sciences at the Fred Hutchinson Cancer Research Center and an Investigator of the Howard Hughes Medical Institute. Her lab studies the kinetochore and how it regulates chromosome segregation. Chromosome mis-segregation results in aneuploidy, a common hallmark of cancer as well hereditary birth defects.
Biggins’ groundbreaking research has been recognized with numerous honors. In 2013, Biggins received the National Academy of Sciences Award in Molecular Biology and the Hutchinson Center McDougall Mentoring Award. In 2015, she was awarded the Novitski Prize from the Genetics Society of America, and was elected to the National Academy of Sciences.
Learn more about Dr. Biggins’ research here: http://research.fhcrc.org/biggins/en.html
- Angelika Amon iBioSeminar: Consequences of Aneuploidy
- Richard McIntosh iBioSeminar: Cell Division in Eukaryotes
- Abby Dernburg iBioSeminar: Chromosome Dynamics during Meiosis
- David Morgan iBioSeminar: Controlling the Cell Cycle
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Asbury CL, Tien JF, & Davis TN. (2011) Kinetochores' gripping feat: conformational wave or biased diffusion? Trends Cell Biol. 21, 38-46
Alushin G & Nogales E. (2011) Visualizing kinetochore architecture. Curr Opin Struct Biol. 21(5):661-9
Musacchio A. (2015) The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics. Curr Biol 25, R1002-18
Gonen S, Akiyoshi B, Iadanza MG, et al. (2012) The structure of purified kinetochores reveals multiple microtubule-attachment sites. Nature Struct Mol Bio 19, 925-929
Akiyoshi B, Sarangapani KK, Powers AF, et al. (2010) Tension directly stabilizes reconstituted kinetochore-microtubule attachments. Nature 438, 576-579