Postdoctoral Position Available

Kirsten Hagstrom, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Program in Molecular Medicine

Other Affiliation(s):
   Cell Dynamics Group
   Interdisciplinary Graduate Program

Chromosome Structure and Segregation During Cell Division

Chromosome condensation, the mechanism that transforms chromosomes from stringy masses into compact rod-shaped structures, is essential for the accurate segregation of the genetic material. My laboratory studies the molecular mechanisms that alter chromosome structure during cell division. This is a fundamentally important question, as defective chromosome segregation can change chromosome number, and may cause cell or organism death, developmental defects, or cancer.

Using the nematode C. elegans as an experimental organism, we combine cell biology, biochemistry, and molecular genetics to examine chromosome segregation proteins. Of particular interest is condensin, a conserved multi-protein complex that reconfigures chromosome structure and promotes chromosome segregation. We have shown in C. elegans that condensin is essential for mitosis and meiosis, and localizes to the centromere. We continue to pursue questions about condensin, such as its composition and function during meiosis, its cell cycle regulation, and its centromeric role, as an inroad for understanding chromosome dynamics.

An exciting new collection of factors essential for chromosome segregation has been obtained through a functional proteomics approach. Sensitive mass spectrometry methods identified a number of proteins associated with condensin subunits after immunoprecipitation. We are depleting these factors by RNA interference, and monitoring the effects by time-lapse microscopy in living embryos carrying GFP-labeled chromosomes and microtubules. Many of the condensin-interacting factors show intriguing chromosome segregation defects, are conserved among organisms, and have not yet been studied.

Figure Legend

Condensin is essential for mitotic chromosome organization and segregation.  In the wild-type 2-cell C. elegans embryo pictured (left), an antibody against the centromere-specific histone HCP-6 localizes to the outer face of condensed chromosomes (HCP-6 green, DNA blue, tubulin red).  When condensin is depleted by RNAi (right), chromosomes fail to condense and segregate properly, and the diffuse chromosomal localization of HCP-6 reflects their disorganization.

Selected Publications

Hagstrom, K.A., and B.J. Meyer. 2003. More than compactor and glue: the many functions of condensin and cohesin. Nat Rev Genet 4: 520-534.

Hagstrom, K.A., V.F. Holmes, N.R. Cozzarelli, and B.J. Meyer. 2002. C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis. Genes Dev 16: 729-742.

Hagstrom, K., M. Muller, and P. Schedl. 1997. A Polycomb and GAGA dependent silencer adjoins the Fab-7 boundary in the Drosophila bithorax complex. Genetics 146: 1365-1380.

Hagstrom, K., M. Muller, and P. Schedl. 1996. Fab-7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex. Genes Dev 10: 3202-3215.

Potential Rotation Projects:

Novel chromosome segregation factors

A collection of proteins essential for proper chromosome segregation has been identified in a proteomics screen. These proteins will help us learn more about the fundamental mechanisms that ensure accurate cell division. Projects investigating these proteins could include any of the following:

• Characterize the RNAi depletion phenotype using time-lapse microscopy, antibody staining, and double RNAi combinations.
• Create a GFP-tagged transgene to follow protein dynamics in living cells.
• Immuno-localization in fixed cells and immunoprecipitation of associated proteins.
• Reiterative proteomics/RNAi to determine protein complexes and expand a protein interaction network.
• Isolate mutant alleles for genetic analysis.
• Perform biochemical assays as appropriate to suspected mechanism.

Condensin function

Condensin is conserved protein complex essential for shaping and separating eukaryotic chromosomes. Exploiting the advantages of the C. elegans system to probe condensin function will provide insights into general mechanisms of chromosome dynamics. Questions to address include:

• What proteins comprise condensin and how many different condensin complexes exist?
• How is condensin cell cycle regulated?
• How does condensin function during meiosis, and is there a distinct meiotic condensin complex?
• What is the role of condensin at the centromere?

Academic Background:

Kirsten Hagstrom received her B.A. in Biology and Music from Oberlin College in 1989, and her Ph.D. in Molecular Biology from Princeton University in 1998. Her graduate research with Dr. Paul Schedl examined the role of chromatin silencers and insulators in regulating gene expression during Drosophila development. She then pursued postdoctoral research with Dr. Barbara Meyer at the University of California at Berkeley, where she studied the function of the condensin complex in C. elegans mitosis and meiosis. She was supported by a fellowship from the Damon Runyan Cancer Research Foundation. Dr. Hagstrom joined the faculty of the Program in Molecular Medicine and the Program in Cell Dynamics in 2004.

Office: Suite 334
Phone: 508-856-6851
E-mail: Kirsten.Hagstrom@umassmed.edu
Keywords: Genetic Systems, Cancer, Cell Biology, Cell Cycle, Organisms - C. elegans

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Postdoctoral Position Available A Postdoctoral Position is available in Dr. Hagstrom's laboratory.  Contact her at the address above for additional details.