Ulrika Westerlind lab

The mucin glycoproteins belong to a class of densely glycosylated proteins and cover the epithelial surfaces with membrane-bound and secreted proteins. These proteins are major components of the mucus protective barrier, which as a part of the innate immune system, constantly sense and clear invading pathogens from the host epithelial environment. At the same time bacteria and viruses have co-evolved with the human host and developed strategies to make use of the mucin carbohydrate ligands to promote virulence factors for instance by adherence to the host cell-surface. Bacteria also secrete glycosidases to cleave-off mono- or oligosaccharides from the mucins and use these saccharides as an energy source or as building blocks to form biofilms to avoid discovery by the immune system.

Partial degradation of the mucin oligosaccharides further promotes proteolytic degradation of the mucins and the mucus protective barrier. In gastrointestinal and chronic airway diseases, the immune system response to external insults of the epithelial tissues (caused by invading pathogens), which may instead of protection also result in inflammation and an environment where bacteria thrive and grow. Through synthesis of extensive carbohydrate and multivalent mucin tandem repeat glycopeptide libraries, we aim to gain understanding of the molecular mechanisms behind the interactions between mucins and the microbiome. The synthetic mucin glycopeptides are immobilized on microarray surfaces to study bacteria adhesive binding events and to map substrate specificity of secreted bacteria glycosidases and mucinases. Our synthetic glycopeptides are further used as model compounds in mass spectrometry based fragmentation studies to improve glycan characterization in glycoproteomic workflows.  

Key methods used in our projects: Carbohydrate and glycopeptide synthesis, glycoprotein semi-synthetic work, glycopeptide microarrays for mapping of protein binding events, mass spectrometry for characterization of oxonium ion fragmentation profiles and glycoproteomics method development.

ImageUlrika Westerlind