Associate 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 by the spliceosome 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. Regarding the first project (splicing) this has been a collaboration with the Armitage and Lopez laboratories to design the optimal combination of pre-mRNAs 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. These interactions ensure that the proper spicing site is chosen to create a coding mRNA and are critical to regulating protein production.
The second project involves the forming constructs of fluorescently labeled nucleic acids and semi-conductor or metallic nanoparticles. The ability of nucleic acids and nucleic acid mimics to self-assemble into well-defined structures makes them useful in constructing novel hybrid materials with unique optical properties. These hybrids have found applications in sensitive detection schemes and as novel probes in microscopy. Many of these structures exploit the ability of gold particles to strongly quench or in some cases to even enhance the emission of nearby dye fluorophores to create probes that are sensitive to local environment. Collaboration with the Ly group is important to this effort because of their ability to design PNAs to which both fluorescent dyes and biological recognition elements can be attached.
Lab Webpage: http://www.chem.cmu.edu/groups/peteanu/