We seek to understand the molecules and forces that determine the orientation of cleavage planes in dividing frog eggs. This will generate fundamental knowledge relevant to division of all human cells, and may inform on the origin of certain types of birth defect. We will use eggs of the frog, Xenopus laevis, and extracts made from eggs that reconstitute the microtubule and actin based processes that organize early embryos in a cell-free system.
Our first aim i s to determine the mechanism by which radial arrays of microtubules, called asters, grow to fill the whole egg.
Our second aim i s to determine how signaling molecules that are recruited to the boundary between two microtubule asters signal to the plasma membrane to position cleavage furrows.
Our third aim i s to determine the mechanisms by which asters position in the egg, and by which centrioles positions inside asters.

Public Health Relevance

We seek to understand the molecules and forces that control the geometry of dividing frog eggs. This will generate fundamental knowledge relevant to division of all human cells, and may inform on the origin of certain types of birth defect.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM039565-31
Application #
9532221
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Deatherage, James F
Project Start
1988-02-01
Project End
2019-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
31
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
Nguyen, P A; Field, C M; Mitchison, T J (2018) Prc1E and Kif4A control microtubule organization within and between large Xenopus egg asters. Mol Biol Cell 29:304-316
Pineda, Javier J; Miller, Miles A; Song, Yuyu et al. (2018) Site occupancy calibration of taxane pharmacology in live cells and tissues. Proc Natl Acad Sci U S A 115:E11406-E11414
Field, Christine M; Mitchison, Timothy J (2018) Assembly of Spindles and Asters in Xenopus Egg Extracts. Cold Spring Harb Protoc 2018:pdb.prot099796
Liu, Ling; Su, Xiaoyang; Quinn 3rd, William J et al. (2018) Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. Cell Metab 27:1067-1080.e5
Boke, Elvan; Mitchison, Timothy J (2017) The balbiani body and the concept of physiological amyloids. Cell Cycle 16:153-154
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Field, C M; Pelletier, J F; Mitchison, T J (2017) Xenopus extract approaches to studying microtubule organization and signaling in cytokinesis. Methods Cell Biol 137:395-435
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Costigliola, Nancy; Ding, Liya; Burckhardt, Christoph J et al. (2017) Vimentin fibers orient traction stress. Proc Natl Acad Sci U S A 114:5195-5200

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