In our research group we are using a combination of in vivo assays, biochemistry and cryo-electron microscopy to study macromolecular complexes of specialized pathogenic organisms. We would like to understand the molecular basis of essential pathways in pathogens and uncover unique structural determinants that could serve as novel targets for antibiotics.
Visualizing unique molecular machines important for the infection process
An intracellular lifestyle is a common strategy for parasites as it provides many advantages such as availability of nutrients and evasion of the host immune system. This strategy is used by prokaryotic and eukaryotic parasites causing a wide range of diseases. Some pathogens have evolved unique and highly specialized molecular systems that allow them to infect, persist, hide and multiply within a host cell.
We are particularly interested in highly divergent and specialized pathogens that have unique ways to infect host cells. We aim to identify and characterize these processes and provide a molecular and structural basis of specialized infection mechanisms.
Organism specific elements in universally conserved assemblies
Many molecular machines are conserved in all living organisms. The ribosome, for example, is responsible for almost all protein synthesis on earth and essential in all living organisms. This importance is highlighted by the fact that numerous antibiotics target this essential macromolecular RNA-protein assembly. Despite their highly conserved central role in all cells, ribosomes of different organisms are diverse in terms of their complex structural composition.
We would like to learn how evolution has shaped the structure and composition of the ribosome in highly divergent and understudied organisms and characterize pathogen-specific differences. Further, we would like to learn if these differences require an organism-specific assembly process and provide a structural basis of ribosome biogenesis in pathogenic organisms.
Cryo-EM density of the small subunit processome – a 70 subunit nucleolar precursor of the small ribosomal subunit.
More information on how eukaryotic ribosomes are assembled in the model organism Saccharomyces cerevisiae.