Speaker
Prof.
Matteo Palassini
(Barcelona)
Description
Due to the small number of molecules involved in
intracellular processes, stochastic fluctuations play an
important role in gene regulation, and possible
constructive effects of noise have received considerable
attention. Another important, but often neglected,
aspect of gene regulation are the long delays involved
in the complex biochemical processes of transcription
and translation.
We study the interplay of intrinsic noise and delay in a
model of the p53 core regulatory network. Recent
experiments found pronounced coordinated oscillations
in the concentrations of proteins p53 and Mdm2 in
individual cells subjected to DNA damage. Oscillations
have also been observed in other systems with
negative feedback, such as the Hes1 and NF-$\kappa$B
systems, and in circadian rhythms. Several mechanisms
have been proposed to explain these findings,
such as deterministic limit cycles (with or without delay)
and noise-induced oscillations in the presence of a
strong separation between fast and slow
reactions.
We consider a birth-and-death master equation model
of the negative feedback loop between p53 and Mdm2,
which does not assume a strong separation of reaction
rates but takes into account the transcriptional and
translational delay (at the price of analytical and
computational complications due to the non-Markovian
dynamics). Via exact stochastic simulations, we find
pronounced noise-induced oscillations in a wide
region of parameters for which there are no sustained
oscillations in the deterministic limit, in qualitative
agreement with the experimental results. We speculate
that this may be a generic mechanism for oscillations
in gene regulatory systems.
Primary author
Prof.
Matteo Palassini
(Barcelona)
