UC Davis

Generally, the biology field has treated cell signaling as if it operates in steady-state conditions, collecting data in bulk measurement assays or at single time points. However, this assumption is now being challenged with the advancement of live-cell imaging tools. Many cellular processes are highly dynamic, for example, the cell cycle, or heterogeneous, like cell signaling. These differences in individual cells play a role in cell fate decisions and behavior, such as proliferation, differentiation, or immune response. Cell signaling is also complex in its spatial organization, whereby information diffuses throughout a monolayer and creates an intricate paracrine network influencing gene expression throughout the tissue. Recently cell signaling dynamics have been shown to drive cellular behavior, yet often a stimulus activates more than a single pathway. This raises the question of which information is most critical in deciding cell fate. In the first part of the dissertation, I explore the current state of live-cell biosensors available, the mechanisms behind signaling dynamics, and how temporal information codes cellular outcomes. In the second section, I specifically focus on one of the most well-studied dynamic systems, the MAPK-ERK pathway. In the second part of the dissertation, I expand my study to include other biosensors including NF-kB, AMPK, and JNK as well. I developed a model of lung epithelium that expresses three live-cell reporter constructs simultaneously to measure their role in determining cytokine production, specifically of interleukin-8 (IL-8). I show that multiple signaling pathways are responsible for regulating IL-8 in a time-dependent manner. This study indicates multifactorial regulation of the cellular immune response.