Multiplexing information flow through dynamic signalling systems

par David RAND (Mathematics Institute & Zeeman Institute for Systems Biology and Infectious Epidemiology Research, University of Warwick, UK.)

mercredi 24 avr. 2019, 14:00 → 15:00 Europe/Paris

Recent work has suggested that in dynamic cellular signalling systems
like NF-κB and ERK the mutual information between input and response is
relatively low and less than 2 bits. On the other hand, it is generally
believed that the NF-κB system uses the information from a large number
of input signals to regulate gene transcription of more than 500 genes
in a highly versatile way. It regulates cell fate and inflammatory
signalling in response to diverse stimuli, including viral and bacterial
pathogens, free radicals, cytokines and growth factors. I will propose a
resolution of this potential paradox by studying signal multiplexing
and its relation to decision-making. I will describe some experiments
that support this idea, discuss the underlying mathematical approach,
explain when systems can and can't multiplex, and model some aspects of
the multiplexing seen in NF-κB. As part of this I will introduce a new
mathematical method for the analysis and simulation of large stochastic
non-linear oscillating systems. This allows an analytic analysis of the
stochastic relationship between input and response and shows that for
tightly-coupled systems like those based on current models for
signalling systems, clocks, and the cell cycle this relationship is
highly constrained and non-generic.