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 #
5R01GM026132-37
Application #
8501500
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Gindhart, Joseph G
Project Start
1978-07-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
37
Fiscal Year
2013
Total Cost
$393,452
Indirect Cost
$155,219
Name
Yale University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Pollard, Thomas D (2017) Nine unanswered questions about cytokinesis. J Cell Biol 216:3007-3016
Akamatsu, Matthew; Lin, Yu; Bewersdorf, Joerg et al. (2017) Analysis of interphase node proteins in fission yeast by quantitative and superresolution fluorescence microscopy. Mol Biol Cell 28:3203-3214
Friend, Janice E; Sayyad, Wasim A; Arasada, Rajesh et al. (2017) Fission yeast Myo2: Molecular organization and diffusion in the cytoplasm. Cytoskeleton (Hoboken) :
Pollard, Thomas D (2017) What We Know and Do Not Know About Actin. Handb Exp Pharmacol 235:331-347
Laplante, Caroline; Pollard, Thomas D (2017) Response to Zambon et al. Curr Biol 27:R101-R102
Laplante, Caroline; Huang, Fang; Tebbs, Irene R et al. (2016) Molecular organization of cytokinesis nodes and contractile rings by super-resolution fluorescence microscopy of live fission yeast. Proc Natl Acad Sci U S A 113:E5876-E5885
Courtemanche, Naomi; Pollard, Thomas D; Chen, Qian (2016) Avoiding artefacts when counting polymerized actin in live cells with LifeAct fused to fluorescent proteins. Nat Cell Biol 18:676-83
Laplante, Caroline; Huang, Fang; Bewersdorf, Joerg et al. (2016) High-Speed Super-Resolution Imaging of Live Fission Yeast Cells. Methods Mol Biol 1369:45-57
Pu, Kai-Ming; Akamatsu, Matthew; Pollard, Thomas D (2015) The septation initiation network controls the assembly of nodes containing Cdr2p for cytokinesis in fission yeast. J Cell Sci 128:441-6
Laplante, Caroline; Berro, Julien; Karatekin, Erdem et al. (2015) Three myosins contribute uniquely to the assembly and constriction of the fission yeast cytokinetic contractile ring. Curr Biol 25:1955-65

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