The remarkable accuracy of cell division in E. coli and related bacteria is partially regulated by the Minprotein system, which prevents division near the cell ends by oscillating spatially from pole to pole. The scientist has recently developed a complete model of the Min system, using only known properties of the proteins, which accurately reproduces the observed oscillations and predicts a finite nucleotide exchange rate for the MinD protein of around one second, a number that has since been experimentally verified to a high degree of accuracy. This proposal concerns efforts to develop particle-level simulations in rod-shaped cells, to capture for the first time the helical polymer dynamics of the Min proteins. In addition, the scientist intends to extend the model to round cells, to determine whether Min oscillations can spontaneously select the long axis of the cell to define the division plane in cocci in the presence of statistical fluctuations. These particle-level simulations provides a starting point for a general understanding of how prokaryotes and eukaryotes can use a reaction-diffusion protein system to target proteins to different locations and to detect their own geometry, and will have broad applications at the expanding interface between large-scale computation and the microscale biology of protein interactions. In order to understand the mechanism behind E. coli's incredible division accuracy, the scientist will undertake experiments incorporating computational results to study the effects of changes in concentration on oscillation period and division accuracy. The theoretical work will be performed in Dr. Ned Wingreen's lab at Princeton University, with experimental resources and training provided by Dr. Bonnie Bassler at Princeton University.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
1K25GM075000-01
Application #
6957517
Study Section
Special Emphasis Panel (ZRG1-MABS (01))
Program Officer
Whitmarsh, John
Project Start
2005-08-01
Project End
2010-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
1
Fiscal Year
2005
Total Cost
$115,727
Indirect Cost
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Tuson, Hannah H; Auer, George K; Renner, Lars D et al. (2012) Measuring the stiffness of bacterial cells from growth rates in hydrogels of tunable elasticity. Mol Microbiol 84:874-91
Ursell, Tristan S; Trepagnier, Eliane H; Huang, Kerwyn Casey et al. (2012) Analysis of surface protein expression reveals the growth pattern of the gram-negative outer membrane. PLoS Comput Biol 8:e1002680
Tropini, Carolina; Huang, Kerwyn Casey (2012) Interplay between the localization and kinetics of phosphorylation in flagellar pole development of the bacterium Caulobacter crescentus. PLoS Comput Biol 8:e1002602
Wang, Siyuan; Furchtgott, Leon; Huang, Kerwyn Casey et al. (2012) Helical insertion of peptidoglycan produces chiral ordering of the bacterial cell wall. Proc Natl Acad Sci U S A 109:E595-604
Daly, Kristopher E; Huang, Kerwyn Casey; Wingreen, Ned S et al. (2011) Mechanics of membrane bulging during cell-wall disruption in gram-negative bacteria. Phys Rev E Stat Nonlin Soft Matter Phys 83:041922
Furchtgott, Leon; Wingreen, Ned S; Huang, Kerwyn Casey (2011) Mechanisms for maintaining cell shape in rod-shaped Gram-negative bacteria. Mol Microbiol 81:340-53
van Teeffelen, Sven; Wang, Siyuan; Furchtgott, Leon et al. (2011) The bacterial actin MreB rotates, and rotation depends on cell-wall assembly. Proc Natl Acad Sci U S A 108:15822-7
Grage, Stephan L; Keleshian, Asbed M; Turdzeladze, Tamta et al. (2011) Bilayer-mediated clustering and functional interaction of MscL channels. Biophys J 100:1252-60
Huang, Kerwyn Casey; Ramamurthi, Kumaran S (2010) Macromolecules that prefer their membranes curvy. Mol Microbiol 76:822-32
Fleming, Tinya C; Shin, Jae Yen; Lee, Sang-Hyuk et al. (2010) Dynamic SpoIIIE assembly mediates septal membrane fission during Bacillus subtilis sporulation. Genes Dev 24:1160-72

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