ESR12 – Targeted cross-linking mass spectrometry and host-pathogen interactions

Faculty of Science and Faculty of Medicine, University of Lund (Sweden)
Bacterial pathogens can form complex protein interaction networks with human host proteins to facilitate bacterial colonization and survival and to avoid immune detection and bacterial clearance. The ‘universe’ of these protein interactions is however largely unknown. The recent development of quantitative and structural mass spectrometry (MS) techniques has provided new possibilities to measure protein-protein interactions in great detail. One of these techniques relies on chemical cross-linking (XL) between adjacent proteins to determine binding interfaces and mode of binding. In recent work, the Malmström group has developed new XL-MS techniques referred to as targeted cross-linking MS (TX-MS) that enables structural investigations of complete protein interaction networks. The predominant aim of this PhD proposal is to investigate structural aspects of protein interaction networks formed between the human pathogen Streptococcus pyogenes and human host proteins. S. pyogenes is a gram-positive bacterium and one of the most important human pathogens associated with considerable morbidity and mortality. The project will involve identification of protein-protein binding interfaces between human host proteins and bacterial surface proteins using state-of-the art quantitative MS and TX-MS techniques. The identified protein binding interfaces will be used to discriminate between highly protective and potentially detrimental antibody responses to further advance the understanding of the development of a severe and invasive disease. The post holder will be trained in a highly interdisciplinary manner, gaining experience in mass-spectrometry, proteomics and bioinformatics.