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Center for Nonlinear Studies |
This talk will address these 4 topics: 1. Bifurcation analysis of the genetic toggle: We developed a detailed kinetic model for the genetic toggle- 2 gene bistable network. The toggle as modeled and constructed experimentally in E. coli is irreversible (i.e. at zero inducer- used to toggle between the two states- values it shows two steady states). Bifurcation analysis using the detailed model suggested that the toggle may operate reversibly. It was also observed that it is much easier to make a single copy toggle reversible. 2. Stochastic analysis of the genetic toggle: Stochastic simulations using Gillespie Stochastic Simulation Algorithm were used to describe the bimodal population arising in the system. We were able to describe the reversible operation parameter conditions for the toggle in terms of a stochastic formalism. With an explanation for reversibility we found the conditions under which the toggle might behave as a stochastic oscillator. Thus we were able to develop a bistable stochastic oscillator from the genetic toggle. Parametric analysis to find out the number of oscillations, the time spent in the high and the low state and the frequency of oscillations was done and successfully explained. 3. Spatio-temporal model for the yeast pheromone pathway: In the systems biology part of this work we looked at developing spatio-temporal models of the yeast pheromone pathway. The pheromone pathway plays the same role as the vertebrate EGFR-Ras-Raf-MEK-ERK pathway. We were able to simulate a model for the pheromone pathway spatially. Further refinement of the intracellular structure of the yeast cell was achieved by using a compartmentalized model with one compartment each for the nucleus and the cytoplasm. 4. Nucleocytoplasmic shuttling of pathway species: The kinetic model contained no information about the spatial information of the species involved in the pathway. Recent literature supports the fact that some of the species in the pathway are shuttled into the nucleus where they become activated and then are transported out. Models of passive diffusion and active transport were developed for the compartmentalized model. Nine cases of import/export by passive diffusion/active transport of unactivated/activated species were studied to see how the pheromone pathway response was altered with each case.
Host: Mike Wall, CCS-3