Ph.D.: University of California at Berkley, 1988
RNA and DNA Catalysis
Bioorganic Research Interests. Recently, an expanding list of RNA and DNA catalysts have been discovered through in vitro selection techniques. Examples to date include acyl transfers, amide synthesis, urea synthesis, Diels-Alder cycloadditions, Michael additions, Aldol condensation, nucleophilic substitutions, porphyin metallations, and enzyme cofactor synthesis. This rapid increase in the number and types of reactions known to be catalyzed by nucleic acids is a result of experiments where a large (typically 1014) library of random sequence is used to select a small (10 - 100) fraction of active catalysts. Moreover, recent advances in the enzymatic modification of RNA and DNA are being used to increase the functional diversity in nucleic acids thereby providing the opportunity for a broader range of chemical catalysis. In our group we continue to explore new organic reactions that may be catalyzed by RNA and DNA.
Our goal is to expand our understanding of what is chemically achievable for RNA and DNA catalysis. Of particular interest to us are cycloaddition reactions that could be used to assemble biologically active organic structures. Diels-Alder, hetero Diels-Alder, [3 + 2] and dipolar cycloadditions are all of interest. Using combinatorial chemistry approaches to prepare new libraries we are studying how nucleic acid sequences can be selected to perform highly chemo-, regio- and steroselective cycloaddition reactions. Our goal is to understand the chemical boundaries for a class or reaction that we know can be catalyzed by RNA or DNA and then use a chemical genomics approach to explore mechanisms in biochemical signaling.
Inorganic Nanoparticle Research Interests. RNA catalysis has now been demonstrated for inorganic reactions. The first example of this new type of RNA catalysis revealed that Pd particle formation could be mediated by specific selected sequences. Subsequent research has shown that different shaped metal particles can be formed from selected sequences with a high degree of shape control. Shape control can be important in determining the catalytic activity or physical property of a metal particle.
The selection of RNA catalysts for the synthesis of catalytic alloys from mixtures of metal precursors is an area of current interest. In addition, we are currently working to expand the range of RNA catalyzed inorganic reactions to include metal-oxygen-metal bonds with the goal of selecting functional (e.g. catalysts, magnets and semiconductors) metal oxide nanomaterials. The long-term research goal is discovery of new catalytic materials for use in alternative energy schema. In this regard RNA mediated selection of mixed metal oxides as methanol and hydrogen fuel cell catalysts is of current interest.
The time has never been more exciting to begin a scientific career. Current computer hardware, software, automation, microscopy and spectroscopic instrumentation make exploring new scientific frontiers possible. Mastering a multidisciplinary program and obtaining the knowledge and skills required to succeed in today's competitive research environment is a shared goal of our lab. We welcome inquires regarding our research programs.