Computational Analysis of Spatial Dynamics of Cell Polarization

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Cell polarity, the asymmetric organization of cellular components, is fundamental to life. Important cell functions such as differentiation and proliferation rely upon spatially and temporally accurate cell polarization and the induced cell morphologenesis. While polarization typically involves signal transduction through certain pathways, many recent experimental and theoretical studies revealed that, besides the feedback regulators, more machineries including substructure of the plasma membrane and intracellular vesicle trafficking are contributing to the architecture of cell polarity and cell morphogenesis. This project is concerned with a mathematical and computational investigation of the establishment and maintenance of cell polarity and the induced cell morphological change during yeast Saccharomyces cerevisiae mating process. The first part of this project is to study the role of microdomains on the cell membrane in cell polarization, tracking directional changes of the stimuli, and attenuating noise present in the signals. The second part will investigate potential mechanisms that maintain the polarized growth of yeast cells during mating, with models including a moving cell membrane. The roles of endocytosis and exocytosis in cell polarization will be studied with these models. A major topic in cell biology is to understand how cells sense and react to a wide variety of stimuli, which convey information essential for their growth, development and functions. Cell polarization, which relies on an asymmetric organization of intracellular components, has been widely acknowledged to be a fundamental process underlying spatial sensing of stimuli. The work seeks to address two important questions in cell biology through mathematical modeling and computation: 1) how is the cell polarity established and maintained? 2) what controls the emergence and dynamics of cell morphogenesis during signal sensing? Our models are based on the known experimental observations of polarized morphological change during yeast mating process, and they incorporate important components in the signaling network. We will investigate how the machineries such as substructure of the cell membrane and vesicle trafficking, participate in generating and retaining cell polarity, and how those machineries are incorporated in cell morphogenesis during yeast mating process. Quantitative studies of cell polarization and cell morphogenesis, based on the systems biology methodology which integrates mathematical modeling with experiments, will improve our understanding on the behavior of cell in response to the environment or its physiological setting. The developed framework and models could be applied to other systems, such as T-cell and neutrophils, which also undergo polarization and morphological changes in response to external signals. The research project is interdisciplinary and will enhance interdisciplinary training at the interface between mathematics and biology for the students associated with the project.