This proposal is devoted to the development and application of tools for solving challenging problems in structural biology with NMR spectroscopy and computational methods. This will be achieved through interactions between investigators at Harvard, MIT and the Rowland Institute. The research plan is focused on structural problems related to control of gene expression and on development of technology to solve these problems. It builds on the complementary expertise and the common interests of the scientists involved. Component #1 (Gerhard Wagner, Timothy Havel, Jeffrey Hoch), NMR and Data Reduction Techniques for Large Biomolecules, will develop the experimental and computational technologies needed to characterize the structure and dynamics of macromolecular complexes. Component #2 (Gerhard Wagner), Protein-DNA and Protein-Protein Interactions of Transcriptional Activators, is focused on the interaction and specificity of interactions, of transcriptional activators with proteins and nueleic acids. Component #3, (Gregory Verdine) Transcriptional Activation by the NFAT-AP-DNA complex, will study interactions of the transcriptional activators NFAT and AP- 1, which control 11-2 expression in leukocytes, with their promoter region. Component #4 (James Williamson), Isotope Labeling of RNA and DNA with 2H and 13C, is focused on methods for producing isotope labeled RNA and DNA and on protein-RNA interactions. Core A (Administration), to be managed by G. Wagner, will provide administrative support to all participants of this program project. Core B (NMR Technology), also managed by G. Wagner, will make the most recent developments in NMR technology available for use in the above projects and port experiments between different brands of spectrometers. Core C (Data Reduction and modeling), managed by T. Havel, will provide support with structure calculations and with novel data processing methods.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG3-BBCA (01))
Program Officer
Wehrle, Janna P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Schools of Medicine
United States
Zip Code
Brazin, Kristine N; Mallis, Robert J; Boeszoermenyi, Andras et al. (2018) The T Cell Antigen Receptor ? Transmembrane Domain Coordinates Triggering through Regulation of Bilayer Immersion and CD3 Subunit Associations. Immunity 49:829-841.e6
Chhabra, Sandeep; Fischer, Patrick; Takeuchi, Koh et al. (2018) 15N detection harnesses the slow relaxation property of nitrogen: Delivering enhanced resolution for intrinsically disordered proteins. Proc Natl Acad Sci U S A 115:E1710-E1719
Zhao, Zhao; Zhang, Meng; Hogle, James M et al. (2018) DNA-Corralled Nanodiscs for the Structural and Functional Characterization of Membrane Proteins and Viral Entry. J Am Chem Soc 140:10639-10643
Hagn, Franz; Nasr, Mahmoud L; Wagner, Gerhard (2018) Assembly of phospholipid nanodiscs of controlled size for structural studies of membrane proteins by NMR. Nat Protoc 13:79-98
Nasr, Mahmoud L; Wagner, Gerhard (2018) Covalently circularized nanodiscs; challenges and applications. Curr Opin Struct Biol 51:129-134
Coote, Paul W; Robson, Scott A; Dubey, Abhinav et al. (2018) Optimal control theory enables homonuclear decoupling without Bloch-Siegert shifts in NMR spectroscopy. Nat Commun 9:3014
Ziarek, Joshua J; Baptista, Diego; Wagner, Gerhard (2018) Recent developments in solution nuclear magnetic resonance (NMR)-based molecular biology. J Mol Med (Berl) 96:1-8
Näär, Anders M (2018) miR-33: A Metabolic Conundrum. Trends Endocrinol Metab 29:667-668
Hyberts, Sven G; Robson, Scott A; Wagner, Gerhard (2017) Interpolating and extrapolating with hmsIST: seeking a tmax for optimal sensitivity, resolution and frequency accuracy. J Biomol NMR 68:139-154
Nasr, Mahmoud L; Baptista, Diego; Strauss, Mike et al. (2017) Covalently circularized nanodiscs for studying membrane proteins and viral entry. Nat Methods 14:49-52

Showing the most recent 10 out of 245 publications