Abstract

This proposal request continued support for the Center of Magnetic Resonance (CMR) at the Francis Bitter National Magnet Laboratory. MIT (Grant RR-00995-18). 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 seven spectrometers currently operating in the facility will be upgraded with new transmitter, receivers, pulse programmer, computer, etc. (2) The facility will expand with the addition of nine additional instruments. These include a new addition to the facility, the Spatial NMR Laboratory containing five spectrometers, a new 600 MHz solution spectrometer, eventually two 750 MHz instruments and high field solid state NMR and EPR/DNP spectrometers. (3) New and continuing areas of interest in the core research program include: (a) RF gradient enhanced spectroscopy, (b) isotopic labeling and spectroscopy of RNA's and RNA/protein complexes, (c) imaging of solids, (d) structural studies of solids via dipolar recouping 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 complexes. (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) NMA binding domain (Lippard) (e) glycoprotein folding (Lansbury), (f) cell function and mRNA translation (Gehrke), (g) field dependence of 13C and 15N relaxation times in proteins (Wagner). Imaging studies will include (a) perfusion imaging (Rosen), (b) creatine kinase and brain energetics (Holtzman), (c) metabolism in human cancer xenograph (Jain), (d) diffusion of small solutes in cartilage (Burstein and Gray) and (e) spectroscopy and imaging of rabbit eyes (Chen). (5) The service component of the facility remains an important function as is evident by the 10 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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000995-20
Application #
2281402
Study Section
Special Emphasis Panel (ZRG7-SSS-Z (09))
Project Start
1976-05-01
Project End
1999-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
20
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

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
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
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
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

Showing the most recent 10 out of 12 publications