PROJECT SUMMARY / ABSTRACT This application outlines our request for funding to procure a new 200keV, energy filtered, intermediate-high voltage transmission electron microscope (IVEM) (Thermo-Fisher/FEI Talos F200C G2). This instrument will be completely unique to the La Jolla, CA research Mesa (and it’s many research organizations) and bring into production use cutting edge (and complementary) methods for energy filter enabled, multiple label transmission electron microscopy (e.g., ColorEM) and high throughput 3D electron microscopic tomography (3D EM) of semi- thick epoxy-embedded samples of cells and tissues (non-Cryo). Procurement of this microscope will address two pressing needs: 1) it will directly support growing demand for these imaging methods/technologies by both local and Nationally distributed NIH investigators, currently users of the National Center for Microscopy and Imaging Research (NCMIR); and 2) it will provide production access to cutting-edge methods previously only available on high-end, specialized platforms built to enable development of methods like ColorEM, (fulfilling a goal of NIH to lower barriers to the use and to promote broader dissemination and impact). As such, it will also propel the democratization of these key technologies. The specified new instrument will be procured at a significantly lower cost, compared to the instrument it will replace, a 20 year old custom-built JEOL 3200 IVEM, soon not maintainable by JEOL. The new tool also simplifies installation, with more modest room requirements, allowing adoption of the methods it enables by more NIH researchers. The platform will be automated and set- up for easy access by the community and be supported by a team of experts in electron microscopy, specimen preparation and data processing, analysis, and visualization. Its environment will also include (and make direct use) of novel high-performance computing and data storage infrastructure of the San Diego Supercomputer Center and its affiliated National Research Platform (NRP).