Following the gradient sensing phase, cells reorganize their internal components into a symmetry-broken configuration, resulting in an elongated cell with a clearly identifiable back, front, and side. This polarized state is coupled to motility through the formation of membrane extensions, pseudopodia, which occur mostly at the front of the cell. Using quantitative measurements on cells that are vertically restricted, we have determined that these pseudopodia are closely correlated with membrane areas (""""""""patches"""""""") of increased concentration of activated Ras, Ras-GTP. What remains unclear, however, is the role Ras-GTP plays in restricting the pseudopodia to the front of the cell. Furthermore, the mechanisms for the transient nature of the patches and pseudopodia are unclear. Finally, there is a vigorous and ongoing debate whether new pseudopodia split off existing ones via a specialized fip-splitting mechanism or whether new pseudopodia are created in a stochastic fashion, largely independent of the location of the existing pseudopod. The goal of this project will be to examine the mechanisms of cell polarity using microfluidics technology in combination with modeling efforts. The quantitative results from the experiments will be used to construct mathematical models. Conversely, through specific predictions, these models will guide the experiments. Again, we think that such two-way communication between experiments and modeling is essential in making progress in understanding the role of polarity in chemotaxis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
2P01GM078586-06
Application #
8316911
Study Section
Special Emphasis Panel (ZRG1-CB-G (40))
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-07-31
Support Year
6
Fiscal Year
2012
Total Cost
$94,786
Indirect Cost
$33,634
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Rappel, Wouter-Jan (2016) Cell-cell communication during collective migration. Proc Natl Acad Sci U S A 113:1471-3
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Kessler, David A; Levine, Herbert (2015) Scaling solution in the large population limit of the general asymmetric stochastic Luria-Delbrück evolution process. J Stat Phys 158:783-805
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Álvarez-González, Begoña; Meili, Ruedi; Bastounis, Effie et al. (2015) Three-dimensional balance of cortical tension and axial contractility enables fast amoeboid migration. Biophys J 108:821-32
Rosengarten, Rafael David; Santhanam, Balaji; Fuller, Danny et al. (2015) Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum. BMC Genomics 16:294

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