Research Capabilities
Characterization of Ex-vivo and In-vivo 1H-NMR Biosignatures of Respiratory Exposure to Model Systems
Slow Magic Angle Spinning (MAS) 1H NMR spectroscopy will be used to monitor biosignatures directly in BALF and explants, and in real-time to better understand the mode of action associated with respiratory exposures to Francisella spp., aiding in the identification of relevant biomarkers.
Slow Magic Angle Spinning (MAS) 1H NMR spectroscopy will be used to monitor biosignatures directly in BALF and lung explants. This method has the potential to increase reliability and sensitivity of detection for specific biosignatures in vivo, increasing our understanding of the mode of action associated with respiratory exposures to Francisella spp. that help identify relevant biomarkers. Slow MAS 1H-NMR will be used to detect metabolites generated in mice exposed to Francisella spp. by the respiratory route, potentially providing a technique for early detection of pulmonary exposure. Pulmonary biosignatures will be induced in mice using quantitative respiratory exposures to our model pathogen. Biosignature accumulation and composition will first be measured in BALF, then in excised, intact lung tissue using slow MAS 1H-NMR. In-vivo protocols will then be developed and optimized leading to live animal studies and the development of dose-response and time-course relationships. Standard magnetic resonance imaging of the lungs before and after pathogen exposure will be performed to detect any accompanying inflammation and determine the relationship between pathogen-induced inflammatory response and specific biosignatures. This work will provide a unique and highly specific method for measuring biosignatures in-vivo over traditional techniques, especially given the heterogeneous nature of lung tissue.