Professor of Chemistry
Recent advances both in optical instrumentation and particularly in the development of fluorescent probes have made it possible to observe single nucleic acid structures both in vitro and within living cells. The result has been an explosive growth in the use of single molecule fluorescence methods to measure DNA and RNA structural fluctuations, folding and unfolding behavior, and interactions with proteins that are critical for processes such as gene regulation and the production of protein within the cell. Observing these phenomena on a single molecule basis allows one to measure their kinetics under native or near native conditions and to identify transient and rare reaction intermediates that may nonetheless prove critical to the overall biological process. This level of detail is impossible to achieve using traditional ‘bulk’ approaches which instead report on the averaged behavior of ~1018 molecules. Our group’s interests lie in applying these new techniques in two areas: (1) kinetic and mechanistic studies of pre-mRNA splicing and debranching and the protein-RNA interactions that mediate that process and (2) exploiting the structural regularity and capacity for self-assembly of nucleic acid and nucleic acid mimics to construct materials with novel optical properties. The first project is a collaboration with the Das laboratory to design the optimal combination of models of lariat RNA and fluorescent probes to measure the kinetics of this important biological process in vitro. The ultimate goal of this work is to obtain insight into the protein-RNA and RNA-RNA interactions that are critical to regulating protein production.
Our group utilizes the structural regularity and capacity for self-assembly of nucleic acid and nucleic acid mimics to construct materials with novel optical properties. One project is a collaboration with the Armitage and Das groups to study energy transfer in arrays of fluophores that are assembled using DNA-based scaffolds. The second involves detailed photophysical studies of constructs containing fluorescently-labeled nucleic acids and semi-conductor or metallic nanoparticles. Such hybrids have found applications in sensitive detection schemes and as novel probes in microscopy by exploiting the ability of gold particles to strongly quench or, in some cases, to enhance the emission of nearby dyes. Collaboration with the Jin (Carnegie Mellon University, Chemistry) and Ly groups are important to this effort because of their ability to design and synthesized atomically-precise gold nanoclusters (Jin) and PNAs (Ly) to which both fluorescent dyes and biological recognition elements can be attached.
Liu, Shengpeng; Delos Santos, Junriz; Armitage, Bruce A.; Peteanu, Linda A. Efficient Light Harvesting and Energy Transfer in Tetrahedral Dye Arrays Constructed from DNA. J. Phys. Chem B (in revision).
Chowdhury, Sanchari; Wu, Zhikun; Jaquins-Gerstl, Andrea; Liu, Shengpeng; Dembska, Anna; Armitage, Bruce A.; Jin, Rongchao; Peteanu, Linda A. Wavelength Dependence of the Fluorescence Quenching Efficiency of Nearby Dyes by Gold Nanoclusters and Nanoparticles: The Roles of Spectral Overlap and Particle Size. J. Phys. Chem. C 2011, 115 (41), pp 20105–20112 DOI: 10.1021/jp204836w
Stadler, Andrea L.; Delos Santos, Junriz O.; Stensrud, Elizabeth S.; Dembska, Anna; Silva, Gloria L.; Liu, Shengpeng, Shank, Nathaniel I.; Kunttas-Tatli,Ezgi; Sobers, Courtney J.; Gramlich, Philipp M. E.; Carell, Thomas; Peteanu, Linda A.; McCartney, Brooke M.; Armitage, Bruce A. Fluorescent DNA Nanotags Featuring Covalently Attached Intercalating Dyes: Synthesis, Antibody Conjugation, and Intracellular Imaging. Bioconjugate Chem. 2011, 22 (8), pp 1491–1502 DOI: 10.1021/bc100485f
Robertson, Kelly L.; Yu, Liping; Armitage, Bruce A.; Lopez, A. Javier; Peteanu, Linda A. Fluorescent PNA Probes as Hybridization Labels for Biological RNA. Biochemistry 2006, 45, 6066-6074