LAUSR

One of the great challenges in biology is to understand the emergence of spatial and temporal order in cellular processes. This challenge is particularly relevant to cell signaling, where the localized assembly and activation of protein complexes is used to control everything from cell fate to hormone release. While several decades of research have yielded many of the players in signaling pathways, most of the fundamental, conceptual questions of how signaling works at a molecular level remain mysterious. Immune cell activation represents an ideal system for understanding the spatial and temporal dynamics of cell signaling since the immune system faces an extreme version of many of the problems that all signaling systems must face: how to discriminate between closely related signals and activate the appropriate pathway even when the amount of signal is vanishingly small. In this paper, we have used high-resolution Total Internal Reflection Fluorescent (TIRF) imaging combined with functionalized supported lipid bilayers and engineered receptors and cell lines to visualize the molecular dynamics of immune signaling pathways. We will give details of our experiments that have revealed how the T cell receptor and IL1 receptor signaling networks activate an immune response.