The Advanced Microscopy and Computational Approaches Core (Core C) will provide advanced imaging and computational approaches to support this Program Project in elucidating the molecular mechanisms of DNA replication stress that drive therapeutic response and resistance in SCLC. The microscopy approaches provided include multi-color STORM imaging, live-cell single-molecule tracking, and time-lapse microscopy of cells and tumoroids using established protocols and methods. Core C will establish automated data analysis pipelines for quantitative analysis of microscopy, sequencing and mass spectrometry data generated by all the Projects, and provide strategies for integration of the different data modalities. Core C will establish an infrastructure for dissemination of data, results, and pipelines, and provide interactive web-based user interfaces to allow the scientific community to easily explore the data generated in the projects. Core C will also develop teaching material covering the microscopy and computational approaches implemented.