Experiments using fluorescent reporters have shown that the spatial distribution of many signaling pathway components is altered following a change in the chemoattractant cAMP concentration. These changes occur during the first 0-10 sec after binding or unbinding of the ligand to the receptors. Within this time frame, the membrane closest to the cAMP source experiences an increase in certain signaling components while other components display an increased concentration at the membrane away from the source. Even though a large number of signaling components have been identified, the precise mechanisms of directional sensing remain unclear. To fully understand these mechanisms it is essential to obtain quantitative data using precisely controlled stimulations. To address these mechanisms, we propose to investigate the initial phase of the chemotaxis process using an approach in which the chemoattractant stimulus can be carefully controlled, both spatially and temporally. The results from these experiments will be integrated into models that, in turn, will guide the experiments. We believe that such interaction of modeling with experimentation is essential for making progress in understanding eukaryotic chemotaxis. Indeed, it is this interaction that has proven to be fruitful during the past 4 years.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM078586-08
Application #
8720782
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
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
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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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