This proposal requests continued support for the MIT/Harvard Center for Magnetic Resonance (CMR) located at the Francis Bitter Magnet Laboratory, MIT (Grant RR-009995-22). During the coming five year grant period we plan significant upgrades of existing equipment, acquisition of new instrumentation, and research initiatives in several new areas: (1) The 19 spectrometers currently operating in the facility will continue to be improved with new transmitters, receivers, pulse programmers, computers, etc. (2) The facility will expand with the addition of four instruments: (a) a 250 GHz EPR/ENDOR spectrometer, (b) a 375 MHz DNP spectrometer, and (c) a 750 MHz/89 mm magnet and console will be completed, and (d) we plan to pursue acquisition of a 900 MHZ magnet and console. (3) New and continuing areas of interest in the core research program include: (a) RF gradient enhanced spectroscopy, (b) high resolution solution NMR spectroscopy of proteins and protein/nucleic acid complexes, (c) imaging of solids, (d) structural studies of solids via dipolar recoupling techniques, (e) structural studies of large proteins including enzyme/substrate inhibitor complexes, beta- amyloid, bacteriorhodopsin, and halorhodopsin, (f) CW and pulsed dynamic nuclear polarization, and (g) high frequency CW and pulsed EPR and ENDOR studies of paramagnetic enzymes and enzyme inhibitor complex, (4) The collaborative research effort will grow significantly and will include Solution NMR investigations of (a) drug induced DNA degradation (Stubbe), (b) human sarcomas (Singer), (c) intermediates in protein folding (KEMP), (D) combinatorial carbohydrate libraries (Seeberger), (3) ferrodoxins (Pochapsky), (f) protein dynamics (Kern), and (g) structural studies of a number of proteins (Wagner). Imaging studies will include development of a number of new techniques and investigation of new systems. (5) The service component of the facility remains an important function as is evident by the 14 proposals from outside investigators who have or plan to use the facility frequently. (6) Plans for training and dissemination include course work in magnetic resonance seminars, and publication in scholarly journals.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000995-25
Application #
6188747
Study Section
Special Emphasis Panel (ZRG3-BMT (03))
Program Officer
Levy, Abraham
Project Start
1976-05-01
Project End
2004-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
25
Fiscal Year
2000
Total Cost
$1,275,596
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Marintchev, Assen; Edmonds, Katherine A; Marintcheva, Boriana et al. (2009) Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136:447-60
Frueh, Dominique P; Arthanari, Haribabu; Koglin, Alexander et al. (2009) A double TROSY hNCAnH experiment for efficient assignment of large and challenging proteins. J Am Chem Soc 131:12880-1
Frueh, Dominique P; Leed, Alison; Arthanari, Haribabu et al. (2009) Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins. J Biomol NMR 45:311-8
Lentz, Margaret R; Westmoreland, Susan V; Lee, Vallent et al. (2008) Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS. Magn Reson Med 59:475-84
Hyberts, Sven G; Heffron, Gregory J; Tarragona, Nestor G et al. (2007) Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129:5108-16
Chen, Jingyang; Dupradeau, Francois-Yves; Case, David A et al. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4'-oxidized abasic sites. Biochemistry 46:3096-107
Lentz, Margaret R; Kim, John P; Westmoreland, Susan V et al. (2005) Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology 235:461-8
Kim, John P; Lentz, Margaret R; Westmoreland, Susan V et al. (2005) Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. AJNR Am J Neuroradiol 26:752-9
Peled, S; Cory, D G; Raymond, S A et al. (1999) Water diffusion, T(2), and compartmentation in frog sciatic nerve. Magn Reson Med 42:911-8
Mo, H; Dai, Y; Pochapsky, S S et al. (1999) 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J Biomol NMR 14:287-8

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