|Professor, Microbiology, Immunology & Molecular Genetics|
|Member, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, JCCC Cancer and Stem Cell Biology Program Area|
Molecular biology of parasitic protozoa I am interested in the molecular biology of parasitic protozoa known as trypanosomes or kinetoplastid protozoa. In particular, we are investigating a novel type of RNA modification phenomenon termed ?RNA editing?, that occurs in the single mitochondrion. mRNA transcripts of the mitochondrial maxicircle DNA molecules are modified after transcription by the insertion and deletion of uridine residues at precise sites within coding regions to form a translatable sequence. The information for this editing is contained in small ?guide RNAs?, which hybridize to the pre-edited mRNA and somehow mediate the transfer of uridines to the editing sites. The guide RNAs are encoded mainly in the thousands of minicircular molecules linked by catenation in the single giant network of DNA present in the single mitochondrion of these cells. In some cases multiple overlapping gRNAs mediate the addition of hundreds of uridines at hundreds of sites. We are studying the mechanism of this unusual process by establishing an in vitro editing system. Several classes of ribonucleoprotein complexes appear to be involved, and these are being dissected and analyzed. Proteins involved in the editing process are being isolated and the genes cloned. In addition, we are interested in the evolution of RNA editing in these ancient lower eukaryotic cells. To this end we are analyzing editing in a variety of kinetoplastid protozoa, whose phylogenetic relationships we have determined. By a comparative analysis we can make some deductions about the evolution of this phenomenon. We are also studying the changes in the editing system that occur during prolonged culture of trypanosomes, which appear to involve the loss of minicircle sequence classes encoding specific guide RNA families. I am also interested in other aspects of the mitochondrial genetic system and mitochondrial biogenesis. Since there are no transfer RNAs encoded in the mitochondrial genome of trypanosomes, all the mt tRNAs must be imported, and the mechanism of this process is being actively studied in my laboratory. Mitochondrial transcription and translation are other processes in which I have a great interest.