Multimodal Intravital Microscope for USC Shared Resource - This proposal is submitted to purchase a new high-end multimodal multiphoton fluorescence microscope, a Leica Stellaris 8 DIVE/FALCON system powered by Chameleon Discovery NX laser from Coherent. The new instrument will be operated and maintained by the Multi-Photon Microscopy Core at the Zilkha Neurogenetic Institute, Keck School of Medicine of USC. The purpose of this new microscope is two-fold: to replace the only currently used system that is aged and failing and to bring currently nonexistent imaging capabilities and versatility for a large user base at USC. This multimodal multiphoton system will provide deep imaging of intact living organs in vivo in small animals and of tissues ex vivo with ultra-high sensitivity, high spatial and temporal resolution that other microscopes currently existing at USC cannot achieve. This new core microscope will tremendously help several key strategic research priorities at KSOM/USC, including to improve our understanding of the miracle of the brain, the normal functioning of the body's organs, the discovery of disease mechanisms and biomarkers, testing novel pharmaceuticals and biomedical devices, and the application of stem cells and regenerative medicine to cure degenerative disorders, and will help to keep USC at the forefront of worldwide biomedical research. This new core microscope is essential for continuing the work of a large research base of 23 NIH-funded investigators who have been long-term users from seven major user groups, including kidney, liver, stem cells, brain, vision science, cancer, and dental imaging representing six USC schools/campuses including Medicine, Engineering, Pharmacy, Dentistry, College and the Children's Hospital of Los Angeles. The new microscope will re-energize USC's research activities and maintain the only available core service for deep tissue intravital imaging, therefore the USC Core Instrumentation Award program is providing significant cost-share ($250,000). The ZNI, which is the academic unit housing this core is fully committed to the ongoing maintenance and operation of the new microscope. The USC Multi-Photon Microscopy Core is an integral part of the USC Center of Excellence in Cell & Tissue Imaging, and the new microscope purchase will meet a strategic need expressed in the USC Plan for Science and Technology Facilities by providing instrumentation and collaborative expertise for biomedical research aimed at improving human health. Project Summary/Abstract