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.

Public Health Relevance

The goal of our research is to better understand chemotaxis of eukaryotic cells. Advances in this field will benefit diagnosis and treatment of medical problems involving cell migration.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
2P01GM078586-06
Application #
8267241
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
2012-09-01
Budget End
2013-07-31
Support Year
6
Fiscal Year
2012
Total Cost
$1,240,562
Indirect Cost
$406,135
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
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; 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
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
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

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