Multiscale Modeling of Feedback Regulation During Cellular Polarity Establishment
Year: 2025
Type: dissertation
Abstract: Cell polarity is essential for various cellular processes, including differentiation, migration, and morphogenesis. Understanding the mechanistic basis of polarity is important for uncovering how cells perform these complex tasks. I used multiscale mechanistic models, including differential equations and particle-based simulations, to study polarity dynamics. Yeast is a well-established model for investigating polarity. In Chapter 2, I show that two coupled positive feedback loops are sufficient to drive early-phase polarity dynamics during yeast mating. In Chapter 3, I demonstrate that addition of a delayed negative feedback loop allows the polarity site to be rapidly dismantled following loss of pheromone signal. Chapter 4 examines how negative feedback via vesicle trafficking disrupts polarity, raising questions about how yeast maintain stable polarity despite the strong disturbing effect. In Chapter 5, I apply the principles of coupled feedback loops to random X chromosome inactivation (XCI) essential for dosage compensation in females. I demonstrate that a positive feedback loop involving the long non-coding RNA Xist and the silencing factor SPEN, coupled with a negative feedback loop with repression of an Xist activator, captures the N-1 rule of random XCI. Together, this work highlights how multiscale mechanistic models offer insights into the regulation of polarity and broader biological processes.
DOI: 10.17615/yt3e-5x47
Author: Guan, Kaiyun
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6887670308
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