B. S., 1978, Colorado State University
Ph.D., 1984, Postdoctoral Fellow, 1985-1988, University of Washington
Postdoctoral Research Scientist, 1988-1991, Seattle Biomedical Research Institute
Department of Microbiology and Molecular Genetics
5174 Biomedical Physical Sciences
Michigan State University
East Lansing, MI 48824
Phone: (517) 884-5353
My primary research interests focus on mechanisms involved in the regulation of mitochondrial gene expression. The complex life cycle of the Trypanosomes offers a unique opportunity to study these types of questions. Trypanosomes are a member of the kinetoplastid protozoa which cause tremendous medical and economic distress in Third World countries. They are responsible for diseases such as Sleeping Sickness, Leishmaniasis, and Chagas disease. During their life cycle they undergo dramatic shifts in their respiratory metabolism as they cycle through both mammalian and insect hosts. The bloodstream forms are completely dependent on glycolysis for their energy supply and lack cytochromes and Kreb cycle enzymes, while the insect forms have a fully functional mitochondrion. The mitochondrial genes are regulated primarily at the post-transcriptional level involving RNA editing. The phenomenon of RNA editing in kinetoplastid protozoans is the most radical form of post-transcriptional alteration known to date. The editing of mRNAs in these organisms involves uridine insertions which can double the size of the transcript. It allows the generation of translatable messages by creating the open reading frames as well as proper initiation and termination signals. The ability to modify RNA transcripts and consequently affect initiation and termination codons and coding sequence has the potential to provide extensive flexibility in organelle biogenesis. The phenomenon is of fundamental importance in understanding how genetic information can be stored and processed.
My interests include defining the structure/function relationships of the RNAs and proteins involved in the editing process. The Editosome carries out both structural and functional roles central to the execution and regulation of this unique process. This process is dynamic and involves an interplay of RNA folding and protein catalysis. We hope to understand in mechanistic/structural terms how the RNAs and proteins interact during the multiple rounds of editing needed to generate a mature transcript. My Laboratory is problem based and uses a variety of techniques. Some experimental approaches include: photoaffinity crosslinking, solution structure probing, native and temperature gradient gel electrophoresis and surface plasmon resonance technology.