Director of the Parasitology Laboratory, professor Madison studies the parasite Trypanosoma brucei, which is a blood-borne pathogen that causes both human and zoonotic disease. T. brucei and related trypanosomatids are early eukaryotes and successful pathogens. Currently no preventative therapies are available and treatment is difficult, despite their knowledge of several unique biological processes with the potential to be exploited as drug targets. One such unusual process is RNA editing. RNA editing is found in many organisms including plants, yeast, humans and other mammals, although the mechanisms of editing are distinct. Within the trypanosomatids RNA editing is achieved by the insertion of non-encoded uridines or the deletion of encoded uridines. In the most extreme cases over 50% of the mature mRNA is the result of post-transcriptional editing. Editing takes place exclusively in the mitochondria, where it is required in order to generate mature mRNAs competent for translation into the correct proteins, and is carried out by a large ribonucleoprotein complex. Her work focuses on the biochemistry of editing by this multiprotein complex. In the lab, they have identified a protein, RNA-Editing Associated Protein-1 (REAP-1), which specifically recognizes RNAs requiring editing. Evidence suggests that REAP-1 acts as a recruitment factor to deliver RNAs to the editing complex. REAP-1 is one of only two proteins that have been identified as components not of the core catalytic complex but of a larger (35-40S) complex believed to function in vivo. Through a combination of genetic and biochemical approaches, current work in the lab involves understanding how REAP-1 specifically recognizes and binds to its RNA targets, identifying other proteins with which REAP-1 interacts and determining how REAP-1 influences editing complex assembly and regulation of RNA editing.

The parasite Trypanosoma brucei is a blood-borne pathogen that causes both human and zoonotic disease. T. brucei and related trypanosomatids are early eukaryotes and successful pathogens. Currently no preventative therapies are available and treatment is difficult, despite our knowledge of several unique biological processes with the potential to be exploited as drug targets. One such unusual process is RNA editing. RNA editing is found in many organisms including plants, yeast, humans and other mammals, although the mechanisms of editing are distinct. Within the trypanosomatids RNA editing is achieved by the insertion of non-encoded uridines or the deletion of encoded uridines. In the most extreme cases over 50% of the mature mRNA is the result of post-transcriptional editing. Editing takes place exclusively in the mitochondria, where it is required in order to generate mature mRNAs competent for translation into the correct proteins, and is carried out by a large ribonucleoprotein complex. Our work focuses on the biochemistry of editing by this multiprotein complex. We have identified a protein, RNA-Editing Associated Protein-1 (REAP-1), which specifically recognizes RNAs requiring editing. Evidence suggests that REAP-1 acts as a recruitment factor to deliver RNAs to the editing complex. REAP-1 is one of only two proteins that have been identified as components not of the core catalytic complex but of a larger (35-40S) complex believed to function in vivo. Through a combination of genetic and biochemical approaches, current work in the lab involves understanding how REAP-1 specifically recognizes and binds to its RNA targets, identifying other proteins with which REAP-1 interacts and determining how REAP-1 influences editing complex assembly and regulation of RNA editing.