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Cell communication across scales: Using single-cell technologies to explore cellular dynamics

Abstract

The ability of a cell to accurate interpret its environment and communicate cues within itself is crucial to survival. How cells orchestrate the transmission of large amounts of information within themselves is a key biological question. From surface-level receptors binding to myriads of extracellular molecules to internal changes in gene expression, cells must process vast amounts of inputs and outputs every minute. This work follows the innerworkings of cells to further understand how cells interpret and respond to their environments. By following the flow of information with a cell, we can parse out the mechanisms by which cell signaling controls response. In this dissertation, I first describe a new suite of in situ technologies that are offering a paradigm shift in the manner in which we can understand biology across scales both large, in terms of the makeup and function of organ systems, to the minute, in terms of intracellular localization of molecules. In the second chapter, I describe how one of these technologies, MERFISH, can pair with live-cell imaging of mouse macrophages to further understand their cellular responses to inflammatory signaling molecules. In the third chapter, I describe a method by which endogenous proteins can be genetically tagged and imaged with individual molecular barcodes to further understand cellular signaling and protein dynamics. In the last chapter, I describe how the cell’s chromatin environment is influenced more by cis regulatory elements than previously imagined. Combined, this dissertation explores several areas of cellular information transfer and communication.

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