It is proposed to continue to operate and to extend the capabilities of the Rockefeller University Biotechnology Research Resource. Emphasis will be placed upon the mass spectrometry of high molecular mass biomolecules. A new focus of the Resource will involve the use of tandem mass spectrometry (MS-MS) as an analytical tool for the detailed structural analysis of biomolecules. Two separate approaches to tandem MS will be followed involving (i) the acquisition and application of a commercial triple- quadrupole mass spectrometer using electrospray ionization and liquid secondary ionization MS, and (ii) the assembly and development of an ultra- high sensitivity matrix-assisted laser desorption time-of-flight-ion trap tandem mass spectrometer. The major subdivisions of the Resource activity will be basic research in mass spectrometry, collaborative research on biomedical problems, and analytical service work. The basic research activities will involve investigations of the physical and chemical phenomena involved in matrix-assisted laser desorption MS and electrospray ionization MS and further improvements to the instrumentation, techniques, and applications of these two powerful new methods. The goal of this work is to measure routinely the molecular mass of any peptide or protein at subpicomole levels. Other basic research will focus on the development of ultra sensitive methods for determining the primary structures of biomolecules. Collaborative projects will involve studies (1) of the contribution of human variation at the apolipoprotein gene loci to atherosclerosis susceptibility (J. Breslow, Rockefeller); (2) towards an understanding of the etiology and pathobiology of scrapie and its related neurological disorders (S. Prusiner, UCSF); (3) towards the development of animal models for Alzheimer's disease (J. Buxbaum, P. Greengard, Rockefeller); (4) to improve the chemistry of peptide synthesis (B. Merrifield, Rockefeller); (5) of the structures of mating pheromones from ciliated protozoa (R.A. Bradshaw, U.C. Irvine); (6) of the chemical structure of cross-linked hemoglobin as a potential blood substitute (J. Manning, Rockefeller); (7) of the structure-function relations of gonadotropins and their role in human reproduction (S. Birken, R. Canfield, Columbia); (8) on the definition of posttranslational modifications of nuclear transcription factors (N. Heintz, Rockefeller); (9) of the structure of bacterial cell wall glycopeptides (A. Tomasz, Rockefeller); (10) of posttranslational modifications in the G-protein ?-subunit (P. Backlund, NIMH); (11) of posttranslational modifications in the anaphylatoxins from human serum (T. Hugli, Scripps); (12) of signal transduction mechanisms focussing on guanine nucleotide-binding regulatory proteins (A. Gilman, U.T. Southwestern Medical Center), amongst others.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000862-28
Application #
6330633
Study Section
Special Emphasis Panel (ZRG3-SSS-6 (16))
Program Officer
Sheeley, Douglas
Project Start
1976-12-01
Project End
2002-02-28
Budget Start
2000-12-01
Budget End
2002-02-28
Support Year
28
Fiscal Year
2001
Total Cost
$915,616
Indirect Cost
Name
Rockefeller University
Department
Miscellaneous
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Manning, Lois R; Popowicz, Anthony M; Padovan, Julio C et al. (2017) Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding. Anal Biochem 519:38-41
Boice, Michael; Salloum, Darin; Mourcin, Frederic et al. (2016) Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells. Cell 167:405-418.e13
Chait, Brian T; Cadene, Martine; Olinares, Paul Dominic et al. (2016) Revealing Higher Order Protein Structure Using Mass Spectrometry. J Am Soc Mass Spectrom 27:952-65
Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Maximizing ion transmission from atmospheric pressure into the vacuum of mass spectrometers with a novel electrospray interface. J Am Soc Mass Spectrom 26:649-58
Mast, Fred D; Rachubinski, Richard A; Aitchison, John D (2015) Signaling dynamics and peroxisomes. Curr Opin Cell Biol 35:131-6
Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Optimizing electrospray interfaces using slowly diverging conical duct (ConDuct) electrodes. J Am Soc Mass Spectrom 26:659-67
Oricchio, Elisa; Papapetrou, Eirini P; Lafaille, Fabien et al. (2014) A cell engineering strategy to enhance the safety of stem cell therapies. Cell Rep 8:1677-1685
Zhong, Yu; Morris, Deanna H; Jin, Lin et al. (2014) Nrbf2 protein suppresses autophagy by modulating Atg14L protein-containing Beclin 1-Vps34 complex architecture and reducing intracellular phosphatidylinositol-3 phosphate levels. J Biol Chem 289:26021-37
Mathur, Aabhas; Blais, Steven; Goparaju, Chandra M V et al. (2013) Development of a biosensor for detection of pleural mesothelioma cancer biomarker using surface imprinting. PLoS One 8:e57681
Peterson, Shaun E; Li, Yinyin; Wu-Baer, Foon et al. (2013) Activation of DSB processing requires phosphorylation of CtIP by ATR. Mol Cell 49:657-67

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