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Dr Dennis Bray

Emeritus Professor (active) Tel: +44 (0)1223 333771, Fax: +44 (0)1223 333786, E-mail: db10009@cam.ac.uk
 

image 1

Above: Network of reactions that mediate chemotaxis in the bacterium E. coli.

Above: Molecular structures of receptors and associated signalling proteins.

  Bacterial Chemotaxis: Using Computer Models to Unravel Mechanism

The set of biochemical reactions by which an E. coli bacterium detects and responds to distant sources of attractant or repellent molecules is probably the simplest and best understood example of a cell-signalling pathway. The pathway has been saturated genetically and all of its protein components have been isolated, measured biochemically and their atomic structures determined. We are using detailed computer simulations, tied to experimental data, to ask how the pathway works as an integrated unit. Increasingly we find that the physical location of molecular components within the molecular jungle of the cell interior is crucial for an understanding of their function. Signal amplification, for example, appears to depend on the propagation of activity across clusters of receptors and associated molecules.

Current interests include the development of a graphical display of swimming bacteria to test their responses to spatial gradients of attractants; use of an individual based stochastic program to analyze the responses of E. coli to conflicting gradients; and Brownian diffusion simulations of the diffusive movements of signalling proteins through the bacterial cytoplasm and their transient association with membrane bound receptors. Please see www.pdn.cam.ac.uk/comp-cell for further information, downloadable programs, and complete publication listing.

Recent References

Andrews, S.S. and Bray, D. (2004). Stochastic simulation of chemical reactions with spatial resolution and single molecule detail. Phys. Biol. 1: 137-151.

Lipkow, K., Andrews, S.S., Bray, D. (2004). Simulated diffusion of CheYp through the cytoplasm of E. coli. J. Bacteriol. 187: 45-53.

Windisch, B., Bray, D., Duke, T. (2006) Balls and chains – a mesoscopic approach to tethered protein domains. Biophys. J. 91: 2388-2392.

Bray, D., Levin, M.D., Lipkow, K. (2007) The Chemotactic behavior of computer-based surrogate bacteria. Current Biology 17: 12-19.

Zonia, L. and Bray, D. (2009) Swimming patterns and dynamics of simulated E. coli bacteria. J.R. Soc. Interface (in press).

Goldman, J.P., Levin, M.D., Bray, D. (2009) Signal amplification in lattice of coupled protein kinases. Molecular BioSystems (in press).