Dr. Sue Biggins

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Fred Hutchinson Cancer Research Center
Basic Sciences Division
Associate MemberAppointed: 2005
University of Washington
School of Medicine
Biochemistry
Affiliate Associate ProfessorAppointed: 2005
Fred Hutchinson Cancer Research Center
Basic Sciences Division
Assistant MemberAppointed: 2000
Professional Headshot of Sue  Biggins

Mailing Address

1100 Fairview Ave. N.
Mailstop A2-168
P.O. Box 19024
Seattle, Washington 98109
United States

Contact Information

Phone: (206) 667-1351
Fax: (206) 667-6526
sbiggins@fhcrc.org

Qualifications

Ph.D., Princeton University, Molecular Biology, 1995.
B.S., Stanford University, Biology, 1990.

Expertise and Research Interests

Regulation of chromosome segregation.

How do cells faithfully inherit a complete set of chromosomes during every cell division? My laboratory is focused on elucidating the mechanisms that govern chromosome segregation. Because aneuploidy is a hallmark of all cancers and many birth defects, studies on chromosome segregation are critical to understanding how cells maintain genomic stability and prevent disease. Chromosomes segregate using their kinetochores, the specialized protein structures that are assembled on centromeric DNA sequences and attach to dynamic spindle microtubules. Sister kinetochores must make bioriented attachments to microtubules from opposite poles. Defects in making bioriented kinetochore attachments are detected by the spindle checkpoint that halts the cell cycle until the errors are corrected. My lab is studying many key questions about chromosome segregation, including how kinetochores assemble, how kinetochores make bioriented microtubule attachments, and how the spindle checkpoint detects and corrects defects in these processes.

One of our interests is a key regulator of chromosome segregation in all eukaryotes, the Ipl1/Aurora protein kinase. Because the Aurora kinases are oncogenes, studies on the budding yeast Ipl1 protein are critical to understanding both chromosome segregation and the maintenance of genomic stability. We previously found that Ipl1 leads to the detachment of kinetochores that are not bioriented, giving the cell another chance to make proper bioriented attachments to kinetochores. We are also studying the opposing phosphatase, Glc7, and have recently found that it silences the spindle checkpoint. Current projects in the lab are directed at identifying key substrates for Ipl1 and Glc7 as well as understanding the precise temporal and spatial regulation of the enzymes.

We are also studying the specialized centromeric chromatin structure that is critical for kinetochore assembly and function. All eukaryotic kinetochores contain a centromeric histone H3 variant (CenH3) that forms a specialized centromeric nucleosome and appears to be the epigenetic mark that specifies the site of kinetochore assembly. We previously discovered that CenH3 is regulated by ubiquitin-mediated proteolysis to restrict CenH3 localization to kinetochores. We have recently identified a ubiquitin ligase that degrades CenH3 that mislocalizes to euchromatin and are currently studying its regulation. We also have a number of projects studying histone modifications that are important for centromeric function.

We have recently developed a method to purify the kinetochore and are using this for a number of structural, biophysical and biochemical studies of kinetochores. In collaboration with Chip Asbury's lab, we are performing biophysical experiments to understand how kinetochores maintain load bearing attachments to dynamic microtubules. We are also collaborating with Tamir Gonen to elucidate structural details about kinetochores and their mode of attachment to microtubules. Finally, we are using this assay to identifiy novel post-translational modifications on kinetochores and to reconstitute the spindle checkpoint in vitro. Taken together, these studies should continue to elucidate new details about the mechanisms of chromosome segregation and thus aid in understanding the generation of aneuploidy and disease progression.

Keywords

COS Keywords:

Cell Biology, Cell Cycle, Genetics, Mitosis, Molecular Biology, Natural Processes Health Safety Medical.

Additional Terms:

Cell Biology, Cell Cycle, Chromosomes, Genetics, Kinetochores, Yeast.

Memberships

American Society for Cell Biology
Genetics Society of America

Honors and Awards

2005-2010, LLS Scholar, LLS
2003-2006, Beckman Young Investigator, Beckman Foundation
2000-2003, Sidney Kimmel Scholar, Sidney Kimmel
1998-2000, ACS Senior Postdoctoral Fellow, ACS
1995-1998, Jane Coffin Childs Postdoctoral Fellow, JCC

Funding Received

  • NIH: Regulation of Centromeric Chromatin, 2007 to 2011.
  • Beckman Foundation: Beckman Award, 2003 to 2006.
  • NIH: Regulation of Chromosome Segregation, 2001 to 2011.
  • Sidney Kimmel Foundation: Kimmel Award, 2000 to 2003.

Publications

  • Ng TM, Waples WG, Lavoie BD, Biggins S (Sep 2009) Pericentromeric sister chromatid cohesion promotes kinetochore biorientation., Molecular biology of the cell, 20 (17), 3818-27 Abstract
  • Pinsky BA, Nelson CR, Biggins S (Jul 2009) Protein phosphatase 1 regulates exit from the spindle checkpoint in budding yeast., Current biology : CB, 19 (14), 1182-7 Abstract
  • Kotwaliwale CV, Frei SB, Stern BM, Biggins S (Sep 2007) A pathway containing the Ipl1/aurora protein kinase and the spindle midzone protein Ase1 regulates yeast spindle assembly., Developmental cell, 13 (3), 433-45 Abstract
  • Furuyama S, Biggins S (Sep 2007) Centromere identity is specified by a single centromeric nucleosome in budding yeast., Proceedings of the National Academy of Sciences of the United States of America, 104 (37), 14706-11 Abstract
  • Collins KA, Camahort R, Seidel C, Gerton JL, Biggins S (Feb 2007) The overexpression of a Saccharomyces cerevisiae centromeric histone H3 variant mutant protein leads to a defect in kinetochore biorientation., Genetics, 175 (2), 513-25 Abstract
  • Kotwaliwale C, Biggins S (Dec 2006) Microtubule capture: a concerted effort., Cell, 127 (6), 1105-8 Abstract
  • Norden C, Mendoza M, Dobbelaere J, Kotwaliwale CV, Biggins S, Barral Y (Apr 2006) The NoCut pathway links completion of cytokinesis to spindle midzone function to prevent chromosome breakage., Cell, 125 (1), 85-98 Abstract
  • Pinsky BA, Kotwaliwale CV, Tatsutani SY, Breed CA, Biggins S (Apr 2006) Glc7/protein phosphatase 1 regulatory subunits can oppose the Ipl1/aurora protein kinase by redistributing Glc7., Molecular and cellular biology, 26 (7), 2648-60 Abstract
  • Pinsky BA, Kung C, Shokat KM, Biggins S (Jan 2006) The Ipl1-Aurora protein kinase activates the spindle checkpoint by creating unattached kinetochores., Nature cell biology, 8 (1), 78-83 Abstract
  • Collins KA, Castillo AR, Tatsutani SY, Biggins S (Dec 2005) De novo kinetochore assembly requires the centromeric histone H3 variant., Molecular biology of the cell, 16 (12), 5649-60 Abstract
  • Pinsky BA, Biggins S (Sep 2005) The spindle checkpoint: tension versus attachment., Trends in cell biology, 15 (9), 486-93 Abstract
  • Kamakaka RT, Biggins S, Histone Variants: Deviants?, Genes & Development, 19(3), 295-310, Feb 2005 Abstract
  • Collins KA, Furuyama S, Biggins S, Proteolysis Contributes to the Exclusive Centromere Localization of The Yeast Cse4/CENP-A Histone H3 Variant, Current Biology : Cb, 14(21), 1968-72, Nov 2004
  • Biggins S, Correcting SYNful Attachments, Nature Cell Biology, 6(3), 181-3, Mar 2004
  • Pinsky BA, Tatsutani SY, Collins KA, Biggins S, An Mtw1 Complex Promotes Kinetochore Biorientation that Is Monitored by the Ipl1/Aurora Protein Kinase, Developmental Cell, 5(5), 735-45, November 2003 Abstract
  • Biggins S, How to successfully start a lab, Cell, 114(1), 16-7, July 2003 Abstract
  • Biggins S, Walczak CE, Captivating capture: how microtubules attach to kinetochores, Current Biology : Cb, 13(11), R449-60, May 2003 Abstract
  • Buvelot S, Tatsutani SY, Vermaak D, Biggins S, The budding yeast Ipl1/Aurora protein kinase regulates mitotic spindle disassembly, Journal of Cell Biology, 160(3), 329-39, February 2003 Abstract
  • Pinsky BA, Biggins S, Top-SUMO wrestles centromeric cohesion, Developmental Cell, 3(1), 4-6, July 2002 Abstract
  • Bhalla N, Biggins S, Murray AW, Mutation of YCS4, a budding yeast condensin subunit, affects mitotic and nonmitotic chromosome behavior, Molecular Biology of the Cell, 13(2), 632-45, February 2002 Abstract
  • Biggins S, Murray AW, The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint, Genes and Development, 15(23), 3118-29, December 2001 Abstract
  • Biggins S, Bhalla N, Chang A, Smith DL, Murray AW, Genes involved in sister chromatid separation and segregation in the budding yeast Saccharomyces cerevisiae, Genetics, 159(2), 453-70, October 2001 Abstract
  • Biggins S, Murray AW, Sister chromatid cohesion in mitosis, Current Opinion in Genetics and Development, 9(2), 230-6, April 1999 Abstract
  • Biggins S, Severin FF, Bhalla N, Sassoon I, Hyman AA, Murray AW, The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast, Genes and Development, 13(5), 532-44, March 1999 Abstract
  • Sullivan DS, Biggins S, Rose MD, The yeast centrin, cdc31p, and the interacting protein kinase, Kic1p, are required for cell integrity, Journal of Cell Biology, 143(3), 751-65, November 1998 Abstract
  • Biggins S, Ivanovska I, Rose MD, Yeast ubiquitin-like genes are involved in duplication of the microtubule organizing center, Journal of Cell Biology, 133(6), 1331-46, June 1996 Abstract
  • Biggins S, Rose MD, Direct interaction between yeast spindle pole body components: Kar1p is required for Cdc31p localization to the spindle pole body, Journal of Cell Biology, 125(4), 843-52, May 1994 Abstract
  • Rose MD, Biggins S, Satterwhite LL, Unravelling the tangled web at the microtubule-organizing center, Current Opinion in Cell Biology, 5(1), 105-15, February 1993 Abstract

Profile Details

Last Verified: 9/9/2009

COS Expertise ID #768558
Reference this profile directly: http://myprofile.cos.com/sbiggins