In this project, we will use newly developed computational methods to address outstanding issues in bacterial chemotaxis. These include the question of how bacteria navigate through complex natural environments; how the flexible tethers associated with the chemotaxis receptors influence adaptation; and whether signaling proteins move between the cytoplasm and the membrane in response to chemotactic stimulation. We propose to tackle these and related issues by existing computational methods already formulated by our group as well as novel programs that we will write for the purpose. We will test and refine our theoretical results experimentally through collaborations with established investigators. Our work will advance the understanding of this bacterial chemotaxis, which has been shown to play a crucial role in the invasiveness of pathogenic bacteria and the formation of biofilms in clinical and industrial settings. From a broader perspective, our work will contribute to the general understanding of signal transduction pathways in both bacterial and eucaryotic cells. Because the chemotaxis pathway of coliform bacteria is so well studied, we have an opportunity to probe it in greater depth than is possible in other cell types. We can therefore address fundamental issues such as the integrative interaction of contiguous components of the pathway, and the constraints imposed by diffusive movements through the cytoplasm. Moreover, the intimate involvement of computational and experimental approaches in our study will both contribute to, and derive benefit from, the raidly expanding area of systems biology. ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-MABS (01))
Program Officer
Rodewald, Richard D
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University of Cambridge
United Kingdom
Zip Code
CB2 1-TN
Zonia, Laura; Bray, Dennis (2009) Swimming patterns and dynamics of simulated Escherichia coli bacteria. J R Soc Interface 6:1035-46
DePristo, Mark A; Chang, Lynne; Vale, Ronald D et al. (2009) Introducing simulated cellular architecture to the quantitative analysis of fluorescent microscopy. Prog Biophys Mol Biol 100:25-32
Silversmith, Ruth E; Levin, Matthew D; Schilling, Elmar et al. (2008) Kinetic characterization of catalysis by the chemotaxis phosphatase CheZ. Modulation of activity by the phosphorylated CheY substrate. J Biol Chem 283:756-65
Bray, Dennis; Levin, Matthew D; Lipkow, Karen (2007) The chemotactic behavior of computer-based surrogate bacteria. Curr Biol 17:12-9
Lipkow, Karen (2006) Changing cellular location of CheZ predicted by molecular simulations. PLoS Comput Biol 2:e39
Grati, M'hamed; Schneider, Mark E; Lipkow, Karen et al. (2006) Rapid turnover of stereocilia membrane proteins: evidence from the trafficking and mobility of plasma membrane Ca(2+)-ATPase 2. J Neurosci 26:6386-95
Andrews, Steven S (2005) Serial rebinding of ligands to clustered receptors as exemplified by bacterial chemotaxis. Phys Biol 2:111-22
Lipkow, Karen; Andrews, Steven S; Bray, Dennis (2005) Simulated diffusion of phosphorylated CheY through the cytoplasm of Escherichia coli. J Bacteriol 187:45-53
Goldman, Jacki; Andrews, Steven; Bray, Dennis (2004) Size and composition of membrane protein clusters predicted by Monte Carlo analysis. Eur Biophys J 33:506-12
Bray, Dennis; Duke, Thomas (2004) Conformational spread: the propagation of allosteric states in large multiprotein complexes. Annu Rev Biophys Biomol Struct 33:53-73

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