Microtubules are cytoskeletal elements responsible for the spatial organization of cells. They carry out critical cellular processes such as chromosome segregation, cell polarization and cell migration. The dynamic behaviors of MT plus ends - their growth, shrinkage, targeting and attachment -- are modulated by a bevy of MT-associated factors. Here, we study the molecular mechanisms that regulate the MT cytoskeleton, using the fission yeast Schizosaccharomyces pombe as a model organism. Our studies focus on elucidating the mechanisms that regulate the transitions between MT growth and shrinkage, namely MT rescue and catastrophe.
Our aims are: 1) to characterize CLASP, a candidate MT rescue factor that stabilizes MTs within the mitotic spindle and interphase MT bundles;2) to determine why MT catastrophe events occur at specific cortical sites at cell tips;3) to investigate possible roles of actin in the nucleus, focusing on its effect on chromosome segregation during mitosis.

Public Health Relevance

Microtubules are dynamic filaments responsible for cell division and determination of cell shape and function. In this proposal we will determine how the growth and shrinkage of microtubules are regulated. These studies will provide greater understanding of how mitotic spindles work and will be relevant for human diseases such as cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM069670-08
Application #
8215710
Study Section
Cell Structure and Function (CSF)
Program Officer
Deatherage, James F
Project Start
2005-02-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2014-01-31
Support Year
8
Fiscal Year
2012
Total Cost
$343,406
Indirect Cost
$127,530
Name
Columbia University (N.Y.)
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Chang, Fred; Atilgan, Erdinc; Burgess, David et al. (2014) Manipulating cell shape by placing cells into micro-fabricated chambers. Methods Mol Biol 1136:281-90
Basu, Roshni; Chang, Fred (2011) Characterization of dip1p reveals a switch in Arp2/3-dependent actin assembly for fission yeast endocytosis. Curr Biol 21:905-16
Minc, Nicolas; Burgess, David; Chang, Fred (2011) Influence of cell geometry on division-plane positioning. Cell 144:414-26
Al-Bassam, Jawdat; Kim, Hwajin; Brouhard, Gary et al. (2010) CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule. Dev Cell 19:245-58
Bathe, Mark; Chang, Fred (2010) Cytokinesis and the contractile ring in fission yeast: towards a systems-level understanding. Trends Microbiol 18:38-45
Chang, Fred; Martin, Sophie G (2009) Shaping fission yeast with microtubules. Cold Spring Harb Perspect Biol 1:a001347
Minc, Nicolas; Bratman, Scott V; Basu, Roshni et al. (2009) Establishing new sites of polarization by microtubules. Curr Biol 19:83-94
Bratman, Scott V; Chang, Fred (2008) Mechanisms for maintaining microtubule bundles. Trends Cell Biol 18:580-6
Bratman, Scott V; Chang, Fred (2007) Stabilization of overlapping microtubules by fission yeast CLASP. Dev Cell 13:812-27
Daga, Rafael R; Yonetani, Ann; Chang, Fred (2006) Asymmetric microtubule pushing forces in nuclear centering. Curr Biol 16:1544-50

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