Despite significant advancements in biosensor engineering, there is a pressing need for new spectrally diverse sensors against an extensive array of biological signals and molecules that enable readout at different time scales. My lab is working on engineering and validating novel probes for multiplexed recording of various signaling pathways in live cells. In particular, I will describe the design and development of genetically encoded molecular ticker tapes for recording transcriptional histories of multiple signaling pathways simultaneously in single cells. The ticker tape readout is based on the fluorescence intensity profile along the thin protein fibers growing bi-directionally in the cytoplasm. The ticker tape temporal resolution varies from 0.5 h to 2-3 h at time scales from days to weeks, depending on cell type and expression method. The immediate applications of ticker tape in cell culture and in vivo will be demonstrated. In addition, I will present novel genetically encoded probes for real-time neuronal activity imaging. I will introduce red-shifted calcium and potassium sensors with improved sensitivity and brightness in neurons, which can report neuronal activity in different model organisms. Finally, I will talk about novel Expansion Microscopy protocols optimized for enhancing FPs' fluorescence retention. The systematic validation of spectrally diverse FPs identified a set of chemically stable FPs covering the entire spectral range, thus enabling multicolor 3D super-resolution microscopy. The best-performing FPs were further used for multicolor super-resolution imaging using the optimized ExM protocol. All the tools presented are freely available to the scientific communities via the https://wekwikgene.wllsb.edu.cn/ platform.