The W.M. Keck Center for Cellular Imaging (KCCI), an internationally recognized center for advanced light microscopy imaging that is particularly known for protein-protein interaction imaging, is requesting to replace the existing 11 years old Biorad Radiance2100 confocal/multiphoton microscopy system with a Zeiss 780 NLO with a QUASAR 34-channel GaAasP high-sensitivity detector and non-descan (GaAasP) detector (NDD). We are also requesting to replace the 11 years old manually tunable Coherent Mira 900 system with a digitally-tunable Chameleon Vision-S ultrafast laser system, to be coupled to the Zeiss 780 NLO systems. KCCI is a University-wide imaging facility, located within walking distance of all the participating investigators. The requested instrument will benefit the basic an clinical scientists of this university;in particular the 10 participating federally funded investigators (Major users) and 5 minor users. The requested Zeiss 780 NLO system with Coherent Chameleon Vision-S 2p laser is unique and, providing users the ability to digitally tune to select the excitation wavelengths (through software) to match exactly the fluorophores in their experimental samples. The higher quantum efficiency (45% at 540nm) GaAsP detector provides better opportunity to excite the sample with less excitation intensity and detecting the weaker photons in tissue and intravital imaging. This instrument is essential for our core investigator group, and will also be critical for training other investigators and students attending the fall semester microscopy course interested in the study of various biological applications in tissues and live animals. There is currently no Zeiss 780 NLO system available at the University of Virginia that has a digitally tunable laser from 690 to 1050 nm for multiphoton microscopy for intravital or deep tissue imaging. KCCI is recognized for its annual hands- on training FRET workshop, held for the past eleven years at the University of Virginia. The requested Zeiss 780 NLO is an advanced technology would help us to advance the methodology in molecular imaging and that will help us to continue our outreach program such as our annual FRET workshop. In summary, the requested instrument will provide the research community at the University of Virginia and beyond with a level of imaging capability that is not currently availabl, and this will enhance significantly ongoing and future research.