Project Summary A group of 12 NIH-funded investigators request funding for the purchase of a Zeiss LSM980 with Airyscan 2 (LSM980-Airyscan 2) laser scanning confocal microscope that will housed in a Biosafety Level 2 (BSL) facility. This will enable our investigators to perform live confocal and super-resolution imaging of cells and organoids/enteroids infected with viruses or bacteria, as well as imaging of complex bacterial communities (biofilms). This microscopy systems addresses a significant unmet need at Baylor College of Medicine, as until recently no BSL2 confocal microscope resource was available for live imaging. The new LSM980-Airyscan 2 will be housed in the BSL2 Microscope Core Laboratory (BMCL) and will replace our current Zeiss LSM510 Meta that is on loan to the BMCL to help assess the technology needs of our user base. The primary application of this microscope will be to perform live imaging studies during the course of microbial infections, which occurs over many hours. The LSM980-Airyscan is optimally suited for these needs because it has both hardware and software features that enable fast-speed and high-resolution imaging but with gentle acquisition conditions to minimize phototoxicity and photobleaching. Thus, the LSM980-Airyscan 2 is an excellent choice for the BMCL core and well-suited for our users' research needs. The Major and Minor users are funded by several NIH Institutes, including The National Institute of Allergy and Infectious Diseases (NIAID) and The National Institute of Digestive, Diabetes, and Kidney Diseases (NIDDK). Additional funding is supported by the U.S. Department of Veterans Affairs and foundations. These investigators aim to add live confocal microscopy to their armamentarium of experimental resources to study mechanisms of pathogen-host interactions, such as enteric virus and bacterial infections, exploitation of host calcium signaling by pathogens, immune cell interactions with bacteria and yeast, and biofilm formation on medical devices. The LSM980-Airyscan 2 will be a central resource of the BMCL and will be the first confocal microscope resource for live imaging of BSL2 agents at Baylor College of Medicine