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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Cell Structure and Function (CSF)
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Deatherage, James F
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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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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