Cells are constantly exposed to changing environmental conditions, and must continually adapt to ensure optimal function. Intracellular signaling must therefore accurately relay extracellular information to enable the proper gene transcriptional program. Increasingly it is becoming clear that cells encode signaling information in amplitude, frequency, and spatial contexts. The dynamic component of signaling necessities complex and thorough measurements to accurately learn how the signal is transduced, and it remains an open challenge to learn all of the protein components that generate and modulate these signals.
During this talk, I will present three systems that use dynamic signaling, and our attempts to link genetics to the encoding and decoding of these signals. Specifically, we look at voltage fluxes in bacteria, calcium signaling in cancer, and pH oscillations in yeast. To investigate these systems, we use a combination of optics, fluorescent reporters, molecular biology, image processing, and data analysis. In each case, we are developing or expanding assays to explore dynamic signaling at new scales. Ultimately, we aim to both understand disease etiology and uncover new small molecule targets that ameliorate dysregulated signaling.