Chemotaxis is the directed movement of cells in a chemical gradient. It plays a major role in a large number of important biological processes, including embryology;wound healing, and cancer metastasis. The main aim of this Program Project is to extend our quantitative studies of chemotaxis using the model system Dictyostelium discoideum. Specifically, we will investigate the chemotactic process by dividing it into three projects with distinct timescales: 1) Directional sensing: the first response (0-10 s) of a cell following the exposure to an external Chemoattractant gradient, 2) Polarity: the subsequent (10-45 s) reorganization of the cytoskeleton, leading to an asymmetric (polarized) cell, and 3) Motility: the eventual (>45 s) process of cell movement. For all projects, we will use a combination of quantitative experiments, aided by the use of microfluidic devices, and modeling approaches to further our insights into the mechanisms of eukaryotic chemotaxis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM078586-07
Application #
8539009
Study Section
Special Emphasis Panel (ZRG1-CB-G (40))
Program Officer
Nie, Zhongzhen
Project Start
2006-07-01
Project End
2017-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
7
Fiscal Year
2013
Total Cost
$1,114,152
Indirect Cost
$391,920
Name
University of California San Diego
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Loomis, William F (2016) A better way to discover gene function in the social amoeba Dictyostelium discoideum. Genome Res 26:1161-4
Camley, Brian A; Zimmermann, Juliane; Levine, Herbert et al. (2016) Emergent Collective Chemotaxis without Single-Cell Gradient Sensing. Phys Rev Lett 116:098101
Rappel, Wouter-Jan (2016) Cell-cell communication during collective migration. Proc Natl Acad Sci U S A 113:1471-3
Bhowmik, Arpan; Rappel, Wouter-Jan; Levine, Herbert (2016) Excitable waves and direction-sensing in Dictyostelium discoideum: steps towards a chemotaxis model. Phys Biol 13:016002
Zimmermann, Juliane; Camley, Brian A; Rappel, Wouter-Jan et al. (2016) Contact inhibition of locomotion determines cell-cell and cell-substrate forces in tissues. Proc Natl Acad Sci U S A 113:2660-5
Bastounis, Effie; Álvarez-González, Begoña; del Álamo, Juan C et al. (2016) Cooperative cell motility during tandem locomotion of amoeboid cells. Mol Biol Cell 27:1262-71
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
Loomis, William F (2015) Genetic control of morphogenesis in Dictyostelium. Dev Biol 402:146-61
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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