Tom Shimitzu (AMOLF Institute, Amsterdam). Biophysics seminar ENS-ESPCI

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Giant fluctuations in a bacterial signaling network revealed by FRET in single cells

January 26th, 1pm at ENS

I will describe recent single-cell FRET experiments on the bacterial chemotaxis network, a protein signaling circuit consisting of thousands of molecules, where we have discovered surprisingly large fluctuations in the absence of changes in gene expression. In wildtype cells, we find that temporal signal fluctuations are much greater than previously conjectured based on motor behavior experiments. Experiments with genetic mutants indicate that there exist at least two sources of noise that contribute to these large fluctuations in wildtype cells: (i) stochastic activities of adaptation enzymes, and (ii) receptor-kinase dynamics in the absence of adaptation. Surprisingly, we find that under certain conditions (ii) can generate fluctuations so large that the signaling activity of the entire cell resembles a stochastic two-state switch (with a timescale 100s). The mechanistic origins of these adaptation-independent fluctuations remain an open question but I will describe current thoughts about this kinetic behavior in the context of Ising models that have enjoyed much success in capturing the steady-state response of receptor-kinase signaling arrays to ligand stimuli.





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