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Simplified models of receptor-ligand binding and intracellular signaling systems
Mathematical Biology| Speaker: | Subhadip Raychaudhuri, UC Davis |
| Location: | 2112 MSB |
| Start time: | Mon, Mar 10 2008, 2:10PM |
Description
Simplified theoretical models of biological processes, such as
receptor-ligand binding mediated cellular signaling, can provide
crucial mechanistic insight such complex processes. I have developed a
simplified minimal model of immune receptor diffusion and clustering in
the form of an immunological synapse during the course of antigen
recognition by adaptive immune cells. This minimal model is based on
the continuous time random walk of receptors with a given waiting time
distribution that arises from binding with antigens of varying
affinity. In the case of a spherical cell surface, space and time
variables get coupled in the waiting time distribution in a
non-separable manner leading to a sub-diffusive behavior that depends
on the antigen affinity. Results obtained from the analytical model
are corroborated by Monte Carlo simulations of the minimal model. In a
separate study, I have developed a minimal signaling network that can
respond to an external stimulus in a strength-dependent manner. Using
Gillespie's stochastic simulation algorithm we show that under the
condition of weak stimulus a three-step fast-slow-fast pathway is
activated where large cell-to-cell stochastic fluctuation dominates the
signaling behavior. Interestingly, results obtained from our minimal
model can capture the essential stochastic signaling in a full-scale
complex signaling network of apoptotic cell death signaling and thus
can serve as a general model of apoptosis signaling.
