The Keyence BZ-X00 is a multi-functional and versatile microcopy platform for cells and tissues. It incorporates 6 objective lenses with magnification power from 2X up to 100X. It can be used to image with white light for histological examination of whole tissue slices and cells in culture, and by using filters for fluorescence imaging across the color spectrum. The BZ-X800 configuration in this proposal includes an integrated heating chamber with CO2 for extended live-cell imaging, facilitated by the included automatic focal plane correction software. It also incorporates an optional grid system for structured illumination that can be inserted before the light hits the sample to remove out of focus light and provide images with the resolution of confocal microscopes. Optional data analysis packages are included for automated stitching of large images, hybrid cell counting and 3D- reconstructions of cells and tissues. It is designed from the ground up as a stand-alone system with an enclosure that replaces the need for a dark room and with software controls that minimize the possibility of user errors leading to hardware malfunctions. ? Lee: Current VA Merit, 5I01 BX003265-05, examining mechanisms of MIF-CD74 signaling in protecting against emphysema through activation of specific cell survival, antioxidant, and DNA repair molecules and the suppression of senescence protein p16. ? Lee: Current DoD Grant, PR150809, is testing MIF augmentation against cigarette smoke exposure-related COPD and its subsequent complication, Streptococcus pneumoniae pneumonia ? Spurney: Pending VA Merit Renewal: I01 BX002984-05 examines the molecular mechanisms that contribute to injury of glomerular podocytes in diabetic kidney disease ? Spurney: Department of Defense grant (PR180545) and an NIH training grant (T32 DK007731) and is a co- investigator on an active R01 grant (R01-DK098135). ? Miller: Current VA Merit, I01 BX001729, is examining molecular mechanisms by which chronic inflammation accelerates vascular disease. Studies are performed in cultured smooth muscle cells and a murine model of carotid injury. ? Miller: Pending VA Merit, I01 BX005308, is a pre-IND enabling study to examine the safety of Synthetic RNA ligands for the treatment of hyperproliferative vascular disease. ? Miller: I01 BX005088 is a four-year Merit that will identify RNA aptamers that selectively bind to inflamed endothelial cells and another aptamer to inhibit smooth muscle cell growth. Studies are performed in cultured cells and murine models of vascular disease. ? Miller: I01 BX005450 is a two-year Merit that proposes to determine whether inactivation of extracellular histones by a previously described synthetic RNA ligand will protect from the development of acute respiratory distress syndrome (ARDS) in COVID-19. These studies are performed in hamster models of COVID-19. ? Pisetsky: VA Merit, 5I01BX003772-02, Cellular Sources of Self Antigen in SLE ? McMahon: VA Merit, VA BX-003478-01. SNO transport regulates endothelial adhesion of RBCs. The goal is to determine the mechanism by which RBCs export and endothelial cells import SNOs, forming a signaling pathway. ? Tighe: The laboratory is interested in mechanisms by which air pollution alters lung structure and function. ? Murdoch: Our studies relate to the impact of chronic inflammation on comorbidities and end organ disease, including airway disease and substance abuse-driven inflammation.
The Keyence BZ-X800 microscope in this proposal will benefit the research aims of five VA investigators in the Major User Group and two VA attending clinician scientists in the Minor User Group. Combined, their research efforts are directed toward some of the most devastating diseases affecting the veteran population: COPD, emphysema, fibrosis, diabetes, cardiovascular disease, and bacterial and viral infections. This instrument will significantly accelerate the pace of discovery for these labs, foster collaboration, and though the use of automated routines for image acquisition and analysis, increase data rigor and reproducibility.
