MULTISCALE MODELING OF FEEDBACK REGULATION DURING CELLULAR POLARITY ESTABLISHMENT

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.