The very first cosmid clone from the Leishmania major genome that we sequenced at Seattle Biomed in 1997 offered insight into the unusual gene organization of trypanosomatid genomes – it contained a divergent strand-switch region (as it turned out, the only one on all of chromosome 1). Over the next 10 years, my laboratory was at the forefront in defining the genomic elements and chromatin modifications involved in transcription initiation in Leishmania, as well as defining many of the protein components of the RNA polymerase II and III initiation and elongation complexes. After a brief hiatus in the late 2000s, these activities have been re-kindled by my involvement (in collaboration with the Borst group in Amsterdam) in showing that the trypanosomatid-specific modified DNA base J plays an important role in transcription termination in Leishmania. I am now PI on an NIAID grant investigating the sequence elements and protein machinery involved J insertion and maintenance, as well as the molecular mechanism(s) underlying its involvement in transcription termination.
Project Keywords: Bioinformatics, Genomics, Parasite Molecular Biology