Understanding the spatiotemporal logic of cellular information processing

Throughout their lives, biological cells integrate millions of dynamic, sparse, and even conflicting environmental cues to make key decisions: proliferate or differentiate, migrate or stay put, live or die. To accomplish these tasks, cells use precisely organized information processing channels that facilitate signal transduction by coupling external stimuli to the intracellular machinery. Because there are no special proteins or genes that are responsible for the selectivity of cellular information flow, the fidelity of signal transduction relies on the spatiotemporal organization of cellular information processing channels. To gain mechanistic understanding of the signaling selectivity facilitated by these channels, we focus on visualizing the nanoscale architecture of cell signaling modules within the ultrastructural context of cell membranes. To this end, we are developing dedicated molecular probes and instrumentation for new hybrid light and electron microscopy methods and building next-generation biophysical tools for time-resolved cryo-vitrification. We are using these tools to visualize the nanoscale dynamics of cellular signaling channels and thereby understand the mechanisms of signaling selectivity in differentiated cells and complex tissues.