Deciphering Signaling Network Dynamics, Structure, and Function - Project Summary Cell survival and function depend on the ability to detect and respond to various environmental cues and intercellular signals, a process governed by complex, dynamic signaling networks. Our research seeks to understand how these networks are regulated, how they encode information through temporal and spatial dynamics, and how they drive critical cellular processes such as growth, migration, metabolism, and survival. To address these questions, we will pursue two complementary research directions. First, we will develop robust, high-throughput tools for tracking signaling network dynamics using highly multiplexed imaging of various genetically encoded fluorescent biosensors. By integrating approaches from synthetic biology, chemical biology, and computational modeling, we aim to investigate how cells interpret and integrate multiple signals to regulate growth, migration, and metabolism. We will also examine how heterogeneous signaling responses across individual cells collectively shape population-level behaviors. Second, we will explore the molecular mechanisms and functional roles of self-organized signaling activities, with a focus on the Ras-PI3K- ERK network. This network exhibits features of excitable systems, such as wave-like propagation of activity across the cell surface, and plays critical roles in proliferation, metabolism, migration, and survival. Dysregulation of this network contributes to developmental disorders, metabolic diseases, and cancer. We will examine how the distinct dynamics of PI3K isoforms relate to their specific functions, and how cell adhesion regulates self-organized signaling behavior. Together, our research takes a multidisciplinary approach to uncover fundamental principles governing signaling network dynamics, mechanisms, and functions. The experimental and computational tools developed through this work will have broad utility across the field of cellular signaling.
