With this application we request funds from the ORD Shared Equipment Evaluation Program (SheEEP) to purchase a new confocal microscope to be housed in the Inflammation Program laboratories of the Iowa City VA Medical Center. Specifically, we seek to obtain a model LSM 880 confocal microscope manufactured by Carl Zeiss, Inc. The rationale for this purchase is threefold. First, our current confocal microscope, a Zeiss LSM 510, is 18 years old, and as of September 2016 will be officially obsolete. As such, parts and maintenance will no longer be available, and the instrument, which plays a critical role in many research programs, will become unusable. Second, we have the opportunity to take advantage of a 20% trade-up discount on purchase of the LSM 880. Third and most importantly, there are several features of the LSM 880 that place it at the forefront of confocal technology. Thus, acquisition of an LSM 880 will support cutting edge research and will allow the development of new research projects and new collaborations among scientists of the Iowa City VA research program, which has a long-standing record of excellence and achievement. Our research portfolio is diverse and includes studies of several infectious diseases, inflammation and immunity, glaucoma and blindness, and heart disease, as well as studies of anxiety, depression, PTSD, Alzheimer's disease, Parkinson's disease and other neurological disorders. Confocal microscopy is important to all these studies as it allows fundamental cellular processes to be visualized at high magnification in live and fixed cells of the immune system, brain, heart and other tissues. Specifically, research groups and projects for which the LSM 880 is critical are: 1) Manipulation of apoptosis, pyroptosis and autophagy in macrophages by Francisella tularensis (Dr. Allen). 2) Induction of neutrophil subtype differentiation and DNA release upon Helicobacter pylori infection (Dr. Allen). 3) Studies of microvesicle (ectosome and exosome) release during bacterial infection (Drs. Allen and Nauseef). 4) Studies of retinal ganglion cell death during glaucoma (Dr. Anderson). 5) The role of podosomes in glaucoma and cancer cell motility (Dr. Anderson). 6) Studies of axonal mitochondrial dynamics in glaucoma (Dr. Anderson). 7) Studies of live Staphylococcus aureus biofilms (Dr. Horswill). 8) Analysis of neutrophil trafficking to sites of parasite infection in the skin, and release of parasite exosomes inside macrophages during infection with Leishmania infantum (Dr. Wilson). 9) Studies of neutrophil plasticity in patients with various infectious and inflammatory disorders (Drs. Wilson and Allen). 10) Studies of Glial Maturation Factor abundance and distribution in the brain with respect to pathogenesis of Alzheimer's and Parkinson's disease, and opportunities for therapeutic intervention (Dr. Zaheer). 11) Analyses of neutrophil granules and phagosomes containing S. aureus (Dr. Nauseef). 12) Studies of B-cell TRAF3 using FRET (Dr. Bishop). 13) Localization of normal and mutated acid-sensing ion channels in the brain to elucidate their functions with respect to synaptic plasticity, anxiety disorders, and PTSD (Dr. Wemmie). Thus, acquisition of an LSM 880 will not merely maintain confocal microscopy at the Iowa City VA. Rather, this cutting edge technology will help to ensure that we remain leaders in our respective fields at the forefront of research to improve Veteran's health.
The central objective of VA research is to improve the health of Veterans. The research programs of the Iowa City VA are among the best in the country and are known for long-standing excellence and achievement. Our research portfolio is diverse and includes studies of several infectious diseases, inflammation and immunity, glaucoma and blindness, heart disease and diabetes, as well as studies of anxiety, depression, PTSD, Alzheimer's disease, Parkinson's disease and other neurological disorders. Confocal microscopy is important to all these studies as it allows fundamental cellular processes to be visualized at high magnification in cells of the immune system, brain, heart and other tissues. We request funds to replace an obsolete confocal microscope. This new instrument, a Zeiss LSM880, will allow us to analyze diverse cell biological processes with unprecedented speed and sensitivity, thereby providing insight into underlying disease mechanisms and leading to new treatments that will advance Veteran's health.