With this proposal, we are requesting funds to acquire a MALDI LTQ Orbitrap XL mass spectrometer from Thermo Scientific for bioimaging at the Public Health Research Institute (PHRI), which will be used under biosafety level 3 (BSL3) biocontainment within the Rutgers Regional Biocontainment Laboratory (RBL). PHRI is a Center within New Jersey Medical School/ Rutgers, the State University of New Jersey. The RBL is one of thirteen national facilities designated by the National Institutes of Health (NIH) for research n biosafety level 3 (BSL3) infectious agents, http://njms.Rutgers.edu/research/rbl/index.cfm. The mass spectrometer will be used to support infectious disease research in the BSL3 facility within the Analytical Imaging Shared Facility. MALDI Mass Spectrometry Imaging (MSI) involves visualization of the 2-dimensional spatial distribution of drugs, drug candidates and discovery compounds and their metabolites, lipids and biomarkers within label-free thin slices of sample, such as animal or human tissue/biopsies, with a spatial resolution of around 10-100mm. The imaging resolution enables the detection of differential distribution and concentration gradients across tissue types within a single tissue slice. For example, adjacent infected and uninfected regions can be compared. The unmatched capabilities of MALDI MS imaging as an in-situ analysis tool offers parallel imaging of potentially thousands of analytes at up to cellular resolution. MSI is a fast evolving technology that can take research on infectious disease pathology and drug discovery to a new level. Our experience housing an imaging mass spectrometer in BSL3 facilities (we are currently the only lab to do so) has demonstrated that demand for this type of instrumentation is very high and increasing. Indeed, we currently cannot accommodate the users need within our institute and have had to turn down multiple requests for collaboration from external investigators. In addition to expanding our user base, the MALDI LTQ Orbitrap XL would bring novel capabilities to PHRI, such as imaging of lipids at the host-pathogen interface, imaging of new drug molecules to eradicate HIV-1 from central nervous system reservoirs, and imaging of markers of microbial virulence. A new MALDI Orbitrap XL in our well-supported facility would expand and promote opportunities for novel BSL3 pathogen research. The outcome will be new and better ways to combat infectious diseases.
The distribution of antibiotics at the site of infection is critical to achieve cure, yet it is poorly understood in the case of dangerous pathogens that require working in high-level biocontainment. MALDI mass spectrometry imaging is ideally suited to visualize the distribution of drugs in infected tissues with complex pathology. Our group at the Public Health Research Institute of Rutgers University is requesting this type of instrument to support improved use of existing antibiotics and discovery of better anti-effective drugs against tuberculosis and other high-threat pathogens.
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