Research
Research
ISG15 Research
ISG15 is a ubiquitin-like protein that is well known to counteract viral and bacterial infections, but the underlying molecular mechanisms are poorly understood. In contrast to ubiquitin and SUMO, the ISG15 substrate repertoire is largely unknown and no binding domains or interaction motifs are described that recognize ISG15. As a consequence, the fate of proteins modified by ISG15 (“ISGylated proteins”) inside infected cells is unknown. We develop novel proteomics-based strategies to identify target proteins and conjugation sites of ISG15 that will help to further elucidate the role of ISGylation in the host defense against infection.
Image to the left: Intracellular lipid droplets and Listeria surrounded by RNF213, a newly discovered sensor for ISG15. (image from Nature Communications https://doi.org/10.1038/s41467-021-26061-w, taken by Radoshevich lab, University of Iowa Health Care, USA).
Immunopeptidomics
We focus on the analysis of antigenic peptides during infection. Although many aspects of the MHC presentation pathway are known in great detail, the rules for peptide selection remain largely unknown. We develop robust pipelines for the LC-MS/MS identification of antigenic peptides presented on infected cells, a technology called immunopeptidomics. Newly identified epitopes and antigens are encoded in novel bacterial mRNA vaccine formulations, for instance in the EU BAXERNA project that we coordinate together with the Martens lab.
Image to the left: Graphical abstract of a proof-of-concept study with Listeria, indicating that newly discovered bacterial antigens provide protection when encoded in mRNA vaccine formulations. (Nature Communications https://doi.org/10.1038/s41467-022-33721-y, image created with BioRender)
Moyamoya research
We aim to solve the unknown etiology of a mysterious cerebrovascular disease called Moyamoya. Genetic mutations in RNF213 are a major risk factor for Moyamoya. Intriguingly, our group discovered RNF213 as an ISG15 sensor and novel antibacterial protein, strongly suggesting a role for the immune response to infection in the development of Moyamoya.
Image to the right: An occluded Moyamoya artery imaged by multi-color high content microscopy.