Alladi Ramakrishnan Hall

Directional Accuracy in a Model of Gradient Signaling during Yeast Mating

Rati Sharma

Dept. of Biophysics Johns Hopkins University Baltimore, USA

The mating response of the yeast Saccharomyces cerevisiae is widely used as a model system for studying chemotropism. Haploid yeast sense nearby cells of the opposite mating type by detecting a pheromone gradient and then polarize and grow a mating projection in the direction of the gradient in an attempt to mate with a partner [1]. Experiments monitoring individual yeast cells in an artificial gradient show that they polarize with a broad distribution of directions centered on the gradient [2], but the probability distribution of the direction is not theoretically understood. In this talk, I will present our hybrid model that uses both deterministic and probabilistic features to study the response of the circuit architecture to a gradient stimulus. In particular, I will discuss our simplified model of the reaction network that leads to the formation of the pheromone-receptor complex and activation of the mitogen-activated protein kinase (MAPK) cascade [3]. The model is simulated using the reaction-diffusion master equation (RDME) [4], with novel gradient boundary conditions accounting for a point pheromone emitter a short distance away, the gradient for which has reached a steady state. In the end, I will present the analysis of the response of the signaling cascade to the gradient for different shapes of the simulation volume and for different positive feedback strengths. The signaling cascade is found to be more efficient in a smaller and more compact simulation volume and the accuracy of the gradient sensing is found to be better with slowly diffusing species in the reaction scheme.
REFERENCES
1. Li Y, Yi M, Zou X. (2013) Identification of the molecular mechanisms for cell-fate selection in budding yeast through mathematical modeling. Biophys J. 104, 2282-2294.
2. Moore T. I., Tanaka H., Kim H. J., Jeon N. L., Yi T. M. (2013) Yeast G-proteins mediate directional sensing and polarization behaviors in response to changes in pheromone gradient direction. Mol Biol Cell. 24, 521-534.
3. Kofahl B, Klipp E. (2004) Modelling the dynamics of the yeast pheromone pathway. Yeast. 21, 831-850.
4. Roberts E, Stone J. E. and Luthey-Schulten Z. (2013) LatticeMicrobes: high-performance stochastic simulation method for the reaction-diffusion master equation J. Comp. Chem. 34, 245-255