The goal of my PhD has been to develop and adapt optical chemical biology approaches to study signal transduction in cells. I developed genetically encoded FRET sensors to monitor with high temporal resolution PARP1-dependent ADP-ribosylation in live cells. I explored CB1 location-dependent functionality by adapting genetic code expansion to generate novel tagging strategies in live cells. Finally, I characterized chemically engineered lipid probes designed to follow lipid transport, metabolism and protein-interactions.