My long-range goal is to understand the mechanism of cytokinesis in enough detail to make useful mathematical model of the process that can predict the results of future experiments. To address my goal during the next five years, we will combine complementary cellular, biochemical, genetic and modeling strategies with three specific aims.
Aim 1. Characterize how cytokinesis-organizing centers called nodes associate with the cell cortex and how node proteins (including Blt1p, anillin Mid1p, Myo2p, F-BAR Cdc15p, formin Cdc12p and IQ-GAP Rng2p) interact during interphase and cytokinesis. This ambitious project combines biochemical and biophysical characterization of each of these proteins and their various interactions with live cell fluorescence microscopy and super-resolution fluorescence microscopy to characterize how these proteins function in cells.
Aim 2. Test the search, capture, pull and release hypothesis for contractile ring assembly to learn how precursor nodes transform into a contractile rings.
Aim 3. Document how the protein components of the contractile ring disperse during ring constriction and to discover the molecular mechanisms controlling the process. The first two projects emphasize the top of the cytokinesis pathway, because I believe that understanding how a cell assembles a contractile ring is the key to understanding the rest of the process. My reason for this belief is that virtually all of the proteins in the contractile ring organizing centers are retained in the mature contractile ring, so it is logical that the pathway of assembly determines the architecture and operations of mature and constricting rings. The third project continues our effort to understand the terminal function of the contractile ring.

Public Health Relevance

We study the molecular basis of cytokinesis. Cytokinesis is the first step in embryonic development and is crucial in stem cell biology. Cytokinesis is vital for wound healing but contributes to uncontrolled cellular proliferation in cancer. Our studies on fission yeast are revealing ancient mechanisms that evolved more than 1 billion years ago and are still used by animal cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM026132-37S1
Application #
8918187
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Gindhart, Joseph G
Project Start
1978-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2015-06-30
Support Year
37
Fiscal Year
2014
Total Cost
$130,921
Indirect Cost
$52,157
Name
Yale University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Stachowiak, Matthew R; Laplante, Caroline; Chin, Harvey F et al. (2014) Mechanism of cytokinetic contractile ring constriction in fission yeast. Dev Cell 29:547-61
Akamatsu, Matthew; Berro, Julien; Pu, Kai-Ming et al. (2014) Cytokinetic nodes in fission yeast arise from two distinct types of nodes that merge during interphase. J Cell Biol 204:977-88
Goss, John W; Kim, Sunhee; Bledsoe, Hannah et al. (2014) Characterization of the roles of Blt1p in fission yeast cytokinesis. Mol Biol Cell 25:1946-57
Arasada, Rajesh; Pollard, Thomas D (2014) Contractile ring stability in S. pombe depends on F-BAR protein Cdc15p and Bgs1p transport from the Golgi complex. Cell Rep 8:1533-44
McCormick, Chad D; Akamatsu, Matthew S; Ti, Shih-Chieh et al. (2013) Measuring affinities of fission yeast spindle pole body proteins in live cells across the cell cycle. Biophys J 105:1324-35
Pollard, Thomas D; De La Cruz, Enrique M (2013) Take advantage of time in your experiments: a guide to simple, informative kinetics assays. Mol Biol Cell 24:1103-10
Tebbs, Irene R; Pollard, Thomas D (2013) Separate roles of IQGAP Rng2p in forming and constricting the Schizosaccharomyces pombe cytokinetic contractile ring. Mol Biol Cell 24:1904-17
Chen, Qian; Nag, Shalini; Pollard, Thomas D (2012) Formins filter modified actin subunits during processive elongation. J Struct Biol 177:32-9
Arasada, Rajesh; Pollard, Thomas D (2011) Distinct roles for F-BAR proteins Cdc15p and Bzz1p in actin polymerization at sites of endocytosis in fission yeast. Curr Biol 21:1450-9
Chen, Qian; Pollard, Thomas D (2011) Actin filament severing by cofilin is more important for assembly than constriction of the cytokinetic contractile ring. J Cell Biol 195:485-98

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