March 16, 2026 2:30pm in ENR2 S215
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When
2:30 – 3:30 p.m., March 16, 2026
Where
Title: Identifying Key Modulators of Cell "Sleep" Across Cell Type and Condition Space
Abstract:
The vast majority of our body cells are asleep (non-dividing) at any given time. The transition between cellular sleep (quiescence) and proliferation is critical to tissue homeostasis and repair. A key determinant of this transition is quiescence depth, with "deep" quiescent cells significantly less likely to re-enter the cell cycle and grow. Our earlier studies showed that the activation threshold of the bistable Rb-E2F gene network (Th.E2F) controls this depth, but the underlying regulatory modulators remain poorly understood across diverse cell types. To explore this, we performed a large-scale computational study of 30,000 theoretical quiescent cell models, each defined by a unique parameter set supporting a functional Rb-E2F switch. Despite the high-dimensional heterogeneity of these models, our analysis reveals a surprising convergence into two distinct regulatory regimes: one dominated by G1 cyclin/cdk-related modulators and the other by Rb/E2F complex-related modulators. Using machine learning-based feature importance, we demonstrate that two key parameters—Rb protein level and dephosphorylation rate—act as the primary determinants of which regulatory group a cell utilizes. This work provides a framework for predicting how different cell types across the "condition space" modulate their quiescence depth to prevent diseases like cancer and aging.