Characterization of single-cell dynamics that lead to collective behaviors

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DESCRIPTION (provided by applicant): The goal of this work is to understand how single-cell signaling dynamics contribute to the coordination of collective behaviors in multicellular systems such as the social amoeba Dictyostelium discoideum. During starvation, the amoebae secrete the signaling molecule cAMP and use it as a cue for the cells to aggregate into a multicellular organism. These signaling molecule dynamics can be measured in individual amoeba using fluorescent sensors in wild type and mutant cells. By confining them to microfluidic devices, the amoebae can be exposed to spatially and temporally varying microenvironments to measure how these changes influence signaling. Combining these techniques, this proposal's targets are (1) to show that single Dictyostelium cells during development are excitable systems, and to develop a quantitative model of their signaling dynamics that accurately predicts their behavior and (2) to identify feedback mechanisms in the single-cell cAMP signaling network. In the long term, the proposed work will pave the way for a multi-cellular model that describes the coordination of collective behavior based on single-cell dynamics. Such a model would aid in identifying universal principles that explain how biological systems coordinate collective behavior and undergo the transition from single- to multicellular-controlled behaviors. Expanding our understanding of these principles and feedbacks will ultimately allow us to find new ways to control these behaviors, potentially revealing new drug and treatment targets for diseases that rely on collective behavior to coordinate their progression.