Invited Academic Seminar Series – Jennifer Lippincott-Schwartz

Abstract:

Advances in mRNA-based imaging technologies are enabling unprecedented views of cellular architecture and dynamics. This talk will present two stories that employ synthetic mRNA to probe the spatial and temporal organization of living cells. First, I will describe a generalizable system for in vitro-transcribed (IVT) mRNAs, optimized for high translational efficiency across multiple cell types while reducing stress pathway activation. This platform, termed mRNAbow, supports simultaneous expression of multiple fluorescent proteins, enabling multiplexed imaging in mammalian cells-including cancer lines, iPSC-derived models, primary cells, and organoids-as well as in vivo contexts such as zebrafish embryos. In a different application, MS2 and SUNTAG-based live-cell reporters were used to visualize mRNA dynamics and translation at single-molecule resolution. We find that translation of mRNAs encoding membrane and secretory proteins is enriched at endoplasmic reticulum (ER) junctions containing the structural protein lunapark and localized adjacent to lysosomes. These results reveal a coupling between ER organization, lysosomal nutrient sensing, and the localized synthesis of secretory and membrane proteins, linking spatial cell architecture to translational control.