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
Levine, Herbert (2014) Learning physics of living systems from Dictyostelium. Phys Biol 11:053011
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Knoch, Fabian; Tarantola, Marco; Bodenschatz, Eberhard et al. (2014) Modeling self-organized spatio-temporal patterns of PIP? and PTEN during spontaneous cell polarization. Phys Biol 11:046002
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Tarantola, Marco; Bae, Albert; Fuller, Danny et al. (2014) Cell substratum adhesion during early development of Dictyostelium discoideum. PLoS One 9:e106574
Camley, Brian A; Zhang, Yunsong; Zhao, Yanxiang et al. (2014) Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns. Proc Natl Acad Sci U S A 111:14770-5
Hu, Bo; Rappel, Wouter-Jan; Levine, Herbert (2014) How input noise limits biochemical sensing in ultrasensitive systems. Phys Rev E Stat Nonlin Soft Matter Phys 90:032702
Camley, Brian A; Zhao, Yanxiang; Li, Bo et al. (2013) Periodic migration in a physical model of cells on micropatterns. Phys Rev Lett 111:158102
Segota, Igor; Mong, Surin; Neidich, Eitan et al. (2013) High fidelity information processing in folic acid chemotaxis of Dictyostelium amoebae. J R Soc Interface 10:20130606

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