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 #
5R01GM039565-30
Application #
9310269
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
2017-08-01
Budget End
2018-07-31
Support Year
30
Fiscal Year
2017
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
02115
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
Presler, Marc; Van Itallie, Elizabeth; Klein, Allon M et al. (2017) Proteomics of phosphorylation and protein dynamics during fertilization and meiotic exit in the Xenopus egg. Proc Natl Acad Sci U S A 114:E10838-E10847
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
Hanley, Mariah L; Yoo, Tae Yeon; Sonnett, Matthew et al. (2017) Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin. Mol Biol Cell 28:1444-1456
Mitchison, Timothy J; Field, Christine M (2017) Spindle-to-Cortex Communication in Cleaving Frog Eggs. Cold Spring Harb Symp Quant Biol 82:165-171
Guild, Joshua; Ginzberg, Miriam B; Hueschen, Christina L et al. (2017) Increased lateral microtubule contact at the cell cortex is sufficient to drive mammalian spindle elongation. Mol Biol Cell 28:1975-1983
Boke, Elvan; Mitchison, Timothy J (2017) The balbiani body and the concept of physiological amyloids. Cell Cycle 16:153-154

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