In this paper we investigate the role of spatial effects in determining the
dynamics
of a subclass of signalling pathways characterised by their ability to
demonstrate
oscillatory behaviour. To this end, we formulate a simple spatial model of the
p53
network that accounts for both a negative feedback and a transcriptional delay.
We show that the formation of protein density patterns can depend on the shape
of the cell, position of the nucleus, and the protein diffusion rates. The
temporal
changes in the total amounts of protein are also subject to spatial influences.
The level of DNA damage required to induce sustained oscillations, for
instance,
depends on the morphology of the cell. The model also provides a new
interpretation
of experimentally observed undamped oscillations in p53 levels in single cells.
Our
simulations reveal that alternate sequences of high- and low-amplitude
oscillations
can occur. We propose that the digital pulses may correspond to snap-shots of
our
high-amplitude sequences. Shorter waiting-times between subsequent time-lapse
fluorescence microscopy images in combination with lower detection thresholds
may reveal the irregular high-frequency oscillations suggested by our spatial
model.