faculty

Professor of Chemistry
Ph.D. - Indian Institute of Technology, Kanpur, India

Solid-State NMR Spectroscopy; Structural Biology of Membrane Proteins; Study of Polymers

Phone: (734) 647-6572
E-mail: ramamoor@umich.edu

Research Group

Membrane proteins act as enzymes, regulate transport processes, and play a central role in intercellular communication. In order to understand the diverse functions of membrane proteins and to engineer these functions for biomedical or biotechnological purposes, it is necessary to determine their high-resolution structure and to describe their dynamics. Structure determination of membrane proteins is one of the most important and challenging aspects of science at the present time. Solid-state NMR spectroscopy is an ideal technique for immobile and non-crystalline proteins that are difficult to study by X-ray crystallography or by solution NMR.

The development of solid-state NMR methods and their applications to determine the structure and describe the dynamics of membrane proteins are the main goals of the research program. Biology of the research program involves the preparation of peptides and proteins associated with membranes through synthetic or molecular biological methods. All aspects of sample preparation are optimized including the incorporation of specific and selective isotopic labels, isolation, purification, and final preparation of NMR samples. Antimicrobial peptides, toxins, cytochrome b5, myelin basic protein, and amyloid peptides are some of the systems currently under investigation by this group. Solid-state NMR experiments on membrane proteins incorporated in oriented and unoriented phospholipid bilayers and solution NMR experiments on membrane proteins in detergent micelles or lipid bicelles are performed to determine the structure of membrane proteins.

Solid-state NMR spectroscopy is one of the premier methods for studying the structure and dynamics of molecules in solids. Ramamoorthy's research program orchestrates the theoretical design, experimental demonstration, and application of new and cutting edge solid-state NMR spectroscopic methods to study the structure and properties of molecules in single crystalline, liquid crystalline, polycrystalline, and amorphous phases. The design of solid-state NMR methods is composed of a variety of sophisticated techniques including specifically constructed multiple radio-frequency pulses, magic-angle spinning, multiple resonance schemes, sensitivity enhancement procedures, selective observation or hybridization of them. This basic research on spin physics encompasses theoretical and experimental aspects of spin engineering, computer simulations, and instrumentation.

AWARDS

• NSF Career Development Award
• Grant-in-Aid Award, American Heart Association
• Research partnership Award, Eli Lilly (2006)
• Young Scientist Award, JEOL Ltd.
• Distinguished Visiting Professor, Osaka University

REPRESENTATIVE PUBLICATIONS

1. J. R. Brender, E. L. Lee, M. A. Cavitt, A. Gafni, D. G. Steel, and A. Ramamoorthy, Amyloid Fiber Formation and Membrane Disruption are Separate Processes Localized in Two Distinct Regions of the Amylin Peptide, J. Am. Chem. Soc., 130, 6424-6429 (2008).

2. D. W. Hoskin and A. Ramamoorthy, Studies on Anticancer Activities of Antimicrobial Peptides, BBA Biomembranes 1778, 357-375 (2008).

3. J. Xu, J. Struppe and A. Ramamoorthy, Two-dimensional homonuclear chemical shift correlation established by the cross-relaxation driven spin diffusion in solids, J. Chem. Phys., 128, 052308 (2008).

4. U.H.N.Durr, K. Yamamoto, S.-C.Im, L. Waskell, and A. Ramamoorthy, Solid-state NMR reveals structural and dynamical properties of a membrane-anchored electron-carrier protein, cytochrome b5, J. Am. Chem. Soc., 129, 6670 (2007).

5. P. Podsiadlo et al., Ultrastrong and stiff layered polymer nanocomposites, Science 318, 80 (2007).

6. S. Dvinskikh, U. H. N. Dürr, K. Yamamoto, and A. Ramamoorthy, High-Resolution 2D NMR Spectroscopy of Bicelles to Measure the Membrane Interaction of Ligands, J. Am. Chem. Soc., 129, 794-802 (2007).

7. S. Dvinskikh, U. H. N. Dürr, K. Yamamoto, and A. Ramamoorthy, A High Resolution Solid State NMR Approach for the Structural Studies of Bicelles, J. Am. Chem. Soc., 128, 6326 (2006).

8. A. Ramamoorthy, S. Thennarasu, D. K. Lee, A. Tan, and Lee Maloy, Solid-State NMR Investigation of the Membrane-Disrupting Mechanism of Antimicrobial Peptides MSI-78 and MSI-594 Derived From Magainin 2 and Melittin, Biophys. J., 91, 206-216 (2006).

9. U.H.N. Dürr, U. S. Sudheendra, and A. Ramamoorthy, LL-37, the only human member of the cathelicidin family of antimicrobial peptides, BBA-Biomembranes, 1758, 1408-1425 (2006).