This Resource develops and uses Multi-isotope Imaging Mass Spectrometry (MIMS), the combination of a novel type of secondary ion mass spectrometer with tracer methods and intensive quantitative image analysis. MIMS provides high mass separation (M/AM >10,000) at high secondary ion transmission, high spatial resolution (35 nm) and has the unique capability of simultaneously recording several atomic mass images. Of the utmost importance, MIMS makes it possible for the first time, at the intracellular level, to simultaneously image the distribution and measure the accumulation of molecules labeled with any isotopes, in particular with stable isotopes, for example 15N. Thus, MIMS allows one to study the localization, the accumulation and the turnover of proteins, fatty acids, sugars and foreign molecules in cellular micro domains;the expression and distribution of DNA and RNA;the migration of donor cells to receiver niches, the nesting of stem cell and the intracellular localization of drugs. Finally, the use of stable isotopes opens a world of labeling possibilities that should revive and expand the use of tracers in humans. The Resource collaborates with researchers in cell biology, pathology, biochemistry, immunology, transplantation, pharmacology, stem cell research, microbiology and virology. Development of an iodine negative primary ion source will open subcellular isotope ratio imaging of secondary positive ions, in particular the experimental use of the multiple stable isotopes of calcium to dissect the function of this essential and ubiquitous intracellular agent, and the quantitative imaging of metallo-enzymes. Study of secondary ion formation will guide labeling schemes. Development of automation will allow us to perform complex analyzes 24/7, decomposing a cell from top to bottom in a succession of hundreds of quantitative atomic mass images, each obtained from the sputtering of a few atomic layers. Powerful software will allow us to rapidly extract and reduce quantitative information from reams of data and in a 3D space. Development of methods for long term labeling of cellular DNA will directly benefit immunology, transplantation, stem cell and cancer research. We will train users by organizing yearly workshop on the theory and practice of MIMS and a workshop on the use of the MIMS data reduction software. We will continue to accumulate on the Resource website information spanning all our procedures, results and happenings. We will make of our Web Site a centralized repository for ourselves and the community of users. This Resource is developing multi-isotope imaging mass spectrometry (MIMS), a new technology that makes it possible to image and quantify molecules within individual mammalian or bacterial cells. Called 'an imaging revolution'as quoted by J. Weitzman (2006, J. Biol. 5:16), MIMS will help solving intractable problems in all fields of biomedical research.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-BCMB-N (40))
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Liu, Christina
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Brigham and Women's Hospital
United States
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Kojima, Toru; Yamada, Hiromi; Isobe, Mitsuru et al. (2014) Compositional changes of human hair melanin resulting from bleach treatment investigated by nanoscale secondary ion mass spectrometry. Skin Res Technol 20:416-21
Jones, David L; Clode, Peta L; Kilburn, Matt R et al. (2013) Competition between plant and bacterial cells at the microscale regulates the dynamics of nitrogen acquisition in wheat (Triticum aestivum). New Phytol 200:796-807
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Steinhauser, Matthew L; Bailey, Andrew P; Senyo, Samuel E et al. (2012) Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism. Nature 481:516-9
Zhang, Duan-Sun; Piazza, Valeria; Perrin, Benjamin J et al. (2012) Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia. Nature 481:520-4
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