Information Transmission and Fluctuations in Signaling Cascades
Speaker: Leonid Mirny , MIT-Harvard HST, Physics
Date: November 15 2004
Time: 11:30AM to 1:00PM
Location: 32 G575
Host: P Clote/ BC & B Berger MIT-CSAIL
Contact: Kathleen Dickey, 617 253-3037, kvdickey@mit.edu
Relevant URL: http://www-math.mit.edu/compbiosem/
Signaling pathways inside cells typically amplify and propagate information by reversibly phosphorylating proteins. Intracellular signalling proteins often have low copy number, and spontaneous fluctuations have a potentially strong impact on these networks. How can a cell behave and respond reliably in spite of this intrinsic stochasticity?
Here we investigate the stochastic dynamics of a generic "biochemical switch", a ubiquitous building block of eukaryotic signalling pathways (MAPK, EGF, PDGF, etc). Considering the switch as an information channel, we attempt to identify mechanisms that facilitate the transfer of information amidst random biochemical fluctuations and parameter variations. We analytically characterize intrinsic fluctuations and switching times in two regimes—hyperbolic (exhibiting graded responses) and ultrasensitive (exhibiting switchlike responses). These two regimes show qualitatively different behaviour. We finally interpolate between these regimes using Monte-Carlo simulations.
Our results show the switch behaves like a low-pass filter, filtering out rapid input fluctuations. The quality of information transmission depends on the number of molecules in the switch. For a given input frequency there is an optimal number of molecules that maximizes information transmission through the switch. We show that (1) a cascade can work reliably and even benefit from a small number of molecules and, (2) there is a limited range of enzymatic kinetic parameters that allow for effective information transmission.
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