Assistant Professor of Chemistry, Molecular & Cell Biology
University of California, Berkeley
"Riboswitching on the Light: Imaging Small Molecules Involved in Bacterial and Immune Signaling"
My lab takes a structure-based design approach to develop fluorescent biosensors for studying the spatiotemporal dynamics of small molecule signals and enzyme cofactors in bacteria. I will describe the rationale behind our development of fluorescent biosensors based on riboswitch scaffolds fused to the dye-binding Spinach aptamer, which show remarkable specificity, affinity, and brightness in live cell imaging. These biosensors have enabled us to perform in essence in vivo biochemistry experiments to visualize the dynamic effects of endogenous chemical cues or inhibitor compounds on enzyme activities in live bacteria. We also have applied these biosensors to make several biological discoveries, including identifying components of a newfound cyclic dinucleotide signaling pathway that regulates how some bacteria sense and attach to surfaces. Finally, the recent discovery that these bacterial signals are immunostimulatory and structurally related to an innate immune signal in mammalian cells has motivated the development of new biosensors and probe compounds.