Speaker
Supriya Krishnamurthy
(KTH and Stockholm University)
Description
We study the stochastic switching behavior of a model
circuit of multisite phosphorylation
and dephosphorylation with feedback. The circuit consists of
a kinase and phosphatase acting
on multiple sites of a substrate that, contingent on its
modification state, catalyzes its
own phosphorylation and, in a symmetric scenario,
dephosphorylation. The symmetric case is
viewed as a cartoon of conflicting feedback that could
result from antagonistic pathways
impinging on the state of a shared component.
We find that multisite phosphorylation is sufficient for bistable behavior under feedback even when catalysis is linear in substrate concentration. Bistability occurs as either a first-order or second-order non-equilibrium phase transition, depending on the network symmetries and the ratio of phosphatase to kinase numbers. We also find that the number of substrate molecules is a key parameter controlling the onset of the bistable regime, fluctuation intensity, and the residence time in a switched state. We compute the phase diagram, fluctuation spectrum and large-deviation properties related to switch memory using functional integral methods from reaction-diffusion theory.
We find that multisite phosphorylation is sufficient for bistable behavior under feedback even when catalysis is linear in substrate concentration. Bistability occurs as either a first-order or second-order non-equilibrium phase transition, depending on the network symmetries and the ratio of phosphatase to kinase numbers. We also find that the number of substrate molecules is a key parameter controlling the onset of the bistable regime, fluctuation intensity, and the residence time in a switched state. We compute the phase diagram, fluctuation spectrum and large-deviation properties related to switch memory using functional integral methods from reaction-diffusion theory.
