We propose to establish a National Research Resource for Imaging Mass Spectrometry at Vanderbilt University School of Medicine, Nashville, TN. The Resource would focus on technology advances and innovation that generally would include next generation hardware, software and methods relevant to direct tissue profiling and imaging using mass spectrometry. At the same time, a number of applications in the biological and medical area that would derive significant benefits from this developing technology will be undertaken. In turn, the technical needs of these biological investigations will feed back and help focus and drive additional technology improvement and innovation. The technology program proposed here would involve significant development of histology directed mass spectrometric profiling and imaging of tissues, a new ion source geometry for transmission geometry laser illumination of tissues for single cell analysis, high spatial resolution imaging down to one micron lateral resolution, high sensitivity profiling and imaging to measure lower abundance species than is now possible, and the development of the relevant biocomputational resources to complement the technological advances and enable it to be routinely used by biologists and medical research investigators who are not experts in the field of the technology. The driving biology would be focused on applications that would require new capabilities, such as high spatial resolution imaging of the serotonin neuron proteome in neurodevelopmental disorders, studies of breast and prostate cancer, age related macular degeneration, selected stem cell analyses, studies of the glomerulus in diabetic nephropathy, molecular presentations in malformed heart valve development, and aspects of tumor angiogenesis and growth. Important activities of the Resource would also involve selected collaborations of NIH sponsored research that would significantly benefit from the developing technology of Imaging Mass Spectrometry, to offer core capabilities that include secondary ion mass spectrometry for ultra high resolution imaging of low MW species, and FT ICR instrumentation and expertise for ultra high mass spectrometric resolution Training and dissemination of the technology as well as the expertise present in the Resource would be accomplished through a yearly short course, individual scientific visits by established scientists and trainees, and publication of the outcomes of both the technology and applications programs.

Public Health Relevance

The Resource is involved the discovery of molecular events that occur in disease using advanced instrumentation that is able to measure minute amounts of material. The Resource includes the development of 'next generation'technologies to make higher sensitivity and higher resolution measurements on tissues than can be done currently and apply these technologies to specific biological projects to study specific diseases, such as cancer, kidney disease, diabetes, and neurological disorders. The outcome of this work will be a new understanding of the biology of health and disease that will lead to new treatment opportunities for patients with these diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
8P41GM103391-02
Application #
8223201
Study Section
Special Emphasis Panel (ZRG1-BCMB-N (40))
Program Officer
Sheeley, Douglas
Project Start
2011-02-15
Project End
2015-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2012
Total Cost
$1,906,854
Indirect Cost
$656,011
Name
Vanderbilt University Medical Center
Department
Biochemistry
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Noble, Kenyaria V; Reyzer, Michelle L; Barth, Jeremy L et al. (2018) Use of Proteomic Imaging Coupled With Transcriptomic Analysis to Identify Biomolecules Responsive to Cochlear Injury. Front Mol Neurosci 11:243
Yang, Bo; Patterson, Nathan Heath; Tsui, Tina et al. (2018) Single-Cell Mass Spectrometry Reveals Changes in Lipid and Metabolite Expression in RAW 264.7 Cells upon Lipopolysaccharide Stimulation. J Am Soc Mass Spectrom 29:1012-1020
Soto, Marion; Orliaguet, Lucie; Reyzer, Michelle L et al. (2018) Pyruvate induces torpor in obese mice. Proc Natl Acad Sci U S A 115:810-815
Cassat, James E; Moore, Jessica L; Wilson, Kevin J et al. (2018) Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions. Sci Transl Med 10:
Ryan, Daniel J; Nei, David; Prentice, Boone M et al. (2018) Protein identification in imaging mass spectrometry through spatially targeted liquid micro-extractions. Rapid Commun Mass Spectrom 32:442-450
Daniels, Anthony B; Froehler, Michael T; Pierce, Janene M et al. (2018) Pharmacokinetics, Tissue Localization, Toxicity, and Treatment Efficacy in the First Small Animal (Rabbit) Model of Intra-Arterial Chemotherapy for Retinoblastoma. Invest Ophthalmol Vis Sci 59:446-454
Grove, Kerri J; Lareau, Nichole M; Voziyan, Paul A et al. (2018) Imaging mass spectrometry reveals direct albumin fragmentation within the diabetic kidney. Kidney Int 94:292-302
Ryan, Daniel J; Spraggins, Jeffrey M; Caprioli, Richard M (2018) Protein identification strategies in MALDI imaging mass spectrometry: a brief review. Curr Opin Chem Biol 48:64-72
Covington, Brett C; Spraggins, Jeffrey M; Ynigez-Gutierrez, Audrey E et al. (2018) Response of Hypogean Actinobacterial Genera Secondary Metabolism to Chemical and Biological Stimuli. Appl Environ Microbiol :
Stark, David T; Anderson, David M G; Kwong, Jacky M K et al. (2018) Optic Nerve Regeneration After Crush Remodels the Injury Site: Molecular Insights From Imaging Mass Spectrometry. Invest Ophthalmol Vis Sci 59:212-222

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