Microscopy Core: Project Summary/Abstract Central to the mission of the Koch Institute is to understand the molecular and cellular changes associated with cancer development and progression and to apply that knowledge to developing new treatments and diagnostic approaches. Advanced state-of-the-art imaging tools are essential for these studies. The Koch Institute Microscopy Core provides a broad range of light microscopy-based imaging systems and related image analysis platforms that enable both ex vivo and intravital imaging of nanoparticles, cells, tissues and tumors. In the current funding period, the capabilities of this Core have been expanded and enhanced. This includes the acquisition of new instrumentation and upgrades to many imaging systems, with support from Institutional funding. Importantly, we have recruited Dr. Jeffrey Kuhn to the Core Leader position. Dr. Kuhn is an interdisciplinary expert in cell biology, single molecule biochemistry, and imaging instrument and software development. Core use by Koch Institute Investigators has been strong during this funding cycle: 77% of Center Members use the Core, account for 94% of Core service use, and include investigators from all three Research Programs. In the upcoming funding period, the Microscopy Core will continue to offer a wide range of state-of-the-art services to support Center Member research programs. The Microscopy Core is committed to maintaining instrumentation and capabilities at the leading edge, and will continue to closely monitor technological improvements and evaluate emerging capabilities in the context of Center Member needs and interests. A primary goal is to conduct a hands-on and complete assessment of Core capabilities and Center Member needs with respect to both instrumentation and data analysis capabilities. Replacement of older instruments and acquisition of new capabilities and upgrades will be guided by Center Member research needs and will be funded by Institutional sources. Specific planned initiatives include: enhancing expertise in single molecule localization microscopy; expanding hands-on training opportunities; developing resources to support advanced image processing, visualization, quantitation and machine learning; and collaborating with other Koch Institute Cores to develop a monthly workshop series to support Center Members’ access to imaging technology platforms and data analysis. This Shared Resource is essential to the success of the Koch Institute mission and provides exceptional value to the CCSG. The requested CCSG budget for Year 49 is increased by 27.2% over the Core CCSG budget for the current period (Year 48), reflecting increased support for expert personnel. The CCSG budgets of other Koch Institute Cores have been reduced to offset the proposed increase in this, and other, Cores.