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 #
2P01GM078586-06
Application #
8316903
Study Section
Special Emphasis Panel (ZRG1-CB-G (40))
Project Start
2006-07-01
Project End
2017-07-31
Budget Start
2012-09-01
Budget End
2013-07-31
Support Year
6
Fiscal Year
2012
Total Cost
$432,378
Indirect Cost
$119,360
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Yue, Haicen; Camley, Brian A; Rappel, Wouter-Jan (2018) Minimal Network Topologies for Signal Processing during Collective Cell Chemotaxis. Biophys J 114:2986-2999
Camley, Brian A (2018) Collective gradient sensing and chemotaxis: modeling and recent developments. J Phys Condens Matter 30:223001
Tu, Yuhai; Rappel, Wouter-Jan (2018) Adaptation of Living Systems. Annu Rev Condens Matter Phys 9:183-205
Camley, Brian A; Zhao, Yanxiang; Li, Bo et al. (2017) Crawling and turning in a minimal reaction-diffusion cell motility model: Coupling cell shape and biochemistry. Phys Rev E 95:012401
Camley, Brian A; Rappel, Wouter-Jan (2017) Physical models of collective cell motility: from cell to tissue. J Phys D Appl Phys 50:
Camley, Brian A; Rappel, Wouter-Jan (2017) Cell-to-cell variation sets a tissue-rheology-dependent bound on collective gradient sensing. Proc Natl Acad Sci U S A 114:E10074-E10082
Rappel, Wouter-Jan; Edelstein-Keshet, Leah (2017) Mechanisms of Cell Polarization. Curr Opin Syst Biol 3:43-53
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) Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance. PLoS Comput Biol 12:e1005008
Rappel, Wouter-Jan (2016) Cell-cell communication during collective migration. Proc Natl Acad Sci U S A 113:1471-3

Showing the most recent 10 out of 58 publications