With increasing antibiotic resistance, bacterial infections remain an important threat to human health. To identify novel targets for therapeutic intervention our group investigates host-bacteria interactions by innovative mass spectrometry (MS)-based approaches. Using Listeria monocytogenes as an intracellular bacterial model pathogen, we focus on the analysis of ubiquitin-like protein modifications of the immune system and the MS-based identification of novel bacterial antigens. In 2023 the group was awarded an ERC Consolidator Grant to investigate rare diseases triggered by infection.
Interests
Bacterial infection
Proteomics
Mass spectrometry
ISG15
Moyamoya disease
Current projects
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. 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.
Immunopeptidomics research: 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.
Moyamoya research: we aim to solve the unknown etiology of a mysterious cerebrovascular disease called Moyamoya. Genetic mutations in ring finger protein 213 (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.
Intracellular lipid droplets and Listeria surrounded by RNF213, a newly discovered sensor for ISG15.
(image from Nature Communications, taken by Radoshevich lab, University of Iowa Health Care, USA)