Department of Anatomy
Signalling in a Molecular Jungle: Insights from Bacterial Chemotaxis
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
and the propagation of activity across clusters of receptors and associated
A suite of algorithms (called Smoldyn - for Smoluchowski Dynamics) was
developed by Steven Andrews to track the diffusive trajectory and chemical
reactions of individual molecules in three dimensions. Karen Lipkow is
now using this program to explore the movements of CheY - the only freely
diffusing protein in the bacterial chemotaxis pathway - through the bacterial
cytoplasm. We are addressing such questions as how quickly CheY diffuses
from the receptors to the flagellar motors? What gradients of CheY are
be set up and how will they depend on external stimuli? We are particularly
interested in how the intracellular location of particular proteins is
determined and whether this is modulated by environmental stimuli.
Bray, D. and Duke, T. (2004). Conformational spread: the propagation of
allosteric states in large multiprotein complexes. Annu. Rev. Biophys.
Biomol. Struct. 33: 53-73.
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.