Gene Expression; Molecular and Cellular Biology; Molecular Basis of Disease; Molecular genetics; Protein Function and Structure; Transcription and Translation
Our laboratory uses genetic, biochemical and molecular biological approaches to study the molecular mechanisms of eukaryotic transcription initiation and regulation. Previous work in our laboratory utilizing both the budding yeast Saccharomyces cerevisiae and human cells resulted in the identification and biochemical characterization of mutants of nuclear RNA polymerase II (RNAPII) and the general transcription factors TFIIB and TFIIF that coordinately affect transcription start site utilization and transcript elongation. These studies supported a model where yeast and human TFIIF induce global conformational changes in RNAPII that result in structural and functional changes in the polymerase active center.
Our current work is aimed toward gaining a better understanding of the mechanisms of kinetoplast transcription by the mitochondrial RNA polymerase of Trypanosoma brucei. T. brucei is a protozoan parasite that is the causative agent of African sleeping sickness (trypanosomiasis) in humans and nagana in animals. Procyclic trypanosomes growing in the midgut of the tsetse fly have fully functional mitochondria whereas trypanosomes in the mammalian bloodstream display repressed mitochondrial function. The mitochondrial DNA in trypanosomes is unusual in its structure, comprising a highly catenated network of maxicircles and minicircles termed kinetoplast DNA (kDNA). Our objective is to elucidate the mechanisms and regulation of T. brucei maxicircle and minicircle transcription.