Deciphering signaling network dynamics, structure, and function

The National Institute of General Medical Sciences awarded The Johns Hopkins University $458,950 on May 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to support research deciphering signaling network dynamics, structure, and function.

The research investigates how cells detect and respond to environmental cues and intercellular signals through complex, dynamic signaling networks. The work pursues two complementary directions: developing high-throughput tools for tracking signaling network dynamics using multiplexed imaging of genetically encoded fluorescent biosensors, integrating synthetic biology, chemical biology, and computational modeling to examine how cells interpret and integrate multiple signals to regulate growth, migration, and metabolism; and exploring molecular mechanisms and functional roles of self-organized signaling activities, with focus on the RAS-PI3K-ERK network, which exhibits excitable system features such as wave-like propagation across the cell surface and plays roles in proliferation, metabolism, migration, and survival. The research also examines how distinct dynamics of PI3K isoforms relate to their specific functions and how cell adhesion regulates self-organized signaling behavior.

Performance occurs in Baltimore, Maryland, with a period of performance from May 1, 2026 through January 31, 2031. The assistance type is a Project Grant. Experimental and computational tools developed through this work are intended to have broad utility across cell signaling research.

Abstract

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.