Research in the lab is focused on specific aspects of gene expression in protozoan-type parasites such as African trypanosomes. Trypanosomes are pathogenic organisms that cause human diseases including African sleeping sickness as well as related diseases in livestock. The resulting suffering and economic loss, mainly in underdeveloped countries, is very large and to date no vaccination for any of the diseases is available.
A second project is aimed at the development of nucleic acid pharmaceuticals for the treatment of trypanosome-induced diseases. We use the SELEX-technology to isolate RNA molecules that specifically bind to surface components of the trypanosome cell. Such “aptamers” can be modified to function as therapeutic and/or diagnostic tools against trypanosome infections.
One focus of our work is an RNA processing reaction known as RNA editing. Editing takes place within the mitochondria of trypanosomes and regulates gene expression by adding and deleting uridine nucleotides into otherwise non-functional primary transcripts. The reaction relies on the catalytic activity of a high molecular mass protein complex, the “editosome”. Recently we determined the structure of the editosome by cryo electron microscopy (cryo-EM). At steady state conditions two different editosome complexes were identified: substrate RNA-bound editosomes with a hydrodynamic size of 40S and RNA substrate free editosomes of 20S.
SFB 902 – Molecular Principles of RNA-based Regulation
HHMI – Howard Hughes Medical Institute