The structural and dynamic basis of RNA signaling in gene regulation of pathogenic bacteria; structure, interactions, dynamics, and function of RNA complexes involved in catalysis; chemical biological methods of labeling RNAs; RNA-Drug interactions, NMR methods development for large macromolecules
American Chemical Society; American Association for the Advancement of Science; National Organization for the Professional Advancement of Black Chemists and Chemical Engineers; RNA Society
Major Recognitions and Honors
Significant Professional Service and Activities
Journals: Current Editorial Boards: The Open Magnetic Resonance Journal. Foundations: National Science Foundation Review Panelist (2005-2006); American Heart Association Review Panelist (2004-2005); Ad Hoc Reviewer for ACS Petroleum Research Fund, U.S.-Israel Binational Science Foundation, Research Corporation, Austrian Science Fund. Grand Awards Judge for the 2003 Intel International Science and Engineering fair (ISEF) of Top High School Science and Engineering Students from Around the World in Cleveland (May 11-17 2003)
Two high-school students, 6 undergraduate students, and 8 postdoctoral associates. Currently mentoring 4 graduate students.
I. Research Focus: Our group is focused on characterizing the structural and dynamics basis of molecular signaling in ribonucleic acids (RNAs) involved in fundamental cellular processes such as catalysis (e.g. splicing by group II introns) and regulation of gene expression (e.g. riboswitches). Splicing defects are implicated in human diseases such as Alzheimer’s, Cystic Fibrosis, and various cancers; riboswitches are recognized as antibacterial drug targets for pathogenic bacteria. Characterizing these RNAs will serve as a guide to the rational design of novel RNA-based drugs.
II. Methodological Approach: We use primarily very high resolution multi-dimensional Nuclear Magnetic Resonance Spectroscopy supplemented by other biophysical tools (X-ray, Fluorescence and Raman Spectroscopies, Small angle x-ray scattering) and chemical biological methods (enzymatic synthesis) to probe the molecular basis of RNA recognition (Dayie KT, 2008, Int. J. Mol. Sci. 9, 1214; Chen et al., 2012, Nucleic Acids Res, 40, 3117; Thakur and Daye, 2012, J. Biomol NMR, 52, 65).
III. Development of New Technologies: Large RNAs pose three serious problems for biophysical characterization: severe overlap and rapid signal decay in NMR, and pervasive misfolding. To address these problems, we continue to develop chemical and biochemical approaches to label nucleotides and make RNA by native preparation methods. By incorporating non-radioactive isotopes and fluorescent dyes at defined sites within RNA, we can easily probe the structure, dynamics and function of large RNAs in their natively folded state (Dayie et al. 1998, J. Magn. Reson. 130, 97; Gumbs et al.,2006, RNA, 12, 1693; Dayie et al., 2007, Anal. Biochem. 362:278; Dayie and Thakur, 2010, J. Biomol. NMR, 47, 19; Luo et al 2011, Nucleic Acids Res, 39, 8559; Arthur et al, 2011, Protein Expr Purif. 76, 229). We are also developing new NMR pulse sequences that make use of these new labels to determine the structures of larger (> 20 kDA) RNAs as shown in these references: Dayie KT, 2005, J. Biomol NMR 32,129 & Gumbs et al., 2006, RNA, 12, 1693; Thakur et al 2012, J. Biomol NMR 52, 103.
IV. Applications to Biological Problems: An emerging tenet of RNA biophysics is that flexibility is intrinsically a necessary part of RNA biomolecular structure and function. Using NMR relaxation measurements and newly developed software for RNA dynamic analysis (Eldho & Dayie, 2007, J. Mol. Biol. 365:930-944), we have shown that dynamics is likely important for the catalytic mechanism of splicing of the Group II Intron ribozyme and we anticipate for riboswitch function. (Eldho & Dayie, 2007, J. Mol. Biol. 365:930-944; Dayie KT, 2008, Int. J. Mol. Sci. 9, 1214-1240; Dayie and Padgett, 2008, RNA, 14:1-7; Chen et al., 2012, Nucleic Acids Res, 40, 3117). These new technologies are being applied to decipher the role of dynamics in molecular recognition utilized in riboswitch RNA based gene regulation.