Associate Professor (b.1967)
B.S. University of North Dakota, 1989
Ph.D. California Institute of Technology, 1994
NIH Postdoctoral Fellow, Harvard University, 1994-96.
Beal Research Group Site
RNA-editing adenosine deaminases. One area under investigation
is the study of the mechanism of RNA-editing adenosine deaminases. These
enzymes have the ability to designate specific adenosines within an mRNA
molecule for deamination. This reaction alters the information content
in the mRNA, thus changing the structure of the encoded protein. One avenue
we are pursuing to investigate this fascinating process is to synthesize
modified nucleosides, which, when incorporated into model substrates,
reveal details of the deamination reaction mechanism. These studies involve
the development of synthesis strategies to protected ribonucleoside phosphoramidites,
protein expression systems to provide the editing enzyme in sufficient
quantity for study and enzyme assays to characterize the resultant RNA-protein
PKR, the RNA Dependent Protein Kinase. We are also studying a human protein kinase (PKR) that is regulated by binding RNA. This enzyme helps fight against viral infection by inhibiting viral protein synthesis in infected cells. Using a variety of chemical and biochemical techniques, we are defining how RNA binds PKR and how the protein kinase activity is controlled by the RNA-binding event (Figure 1).
The libraries are composed of peptides that have an intercalator (acridine or quinoline) embedded in the peptide backbone we call PICs (peptide-intercalator conjugates). In a typical screen for RNA-binding PICs, a fluorescently labeled RNA is bound to the library members covalently attached to solid phase synthesis beads. The structure of the PIC is then determined by tandem mass spectrometry.