How do we live with trillions of intestinal bacteria without getting sick? The answer lies in defense mechanisms of the mucus layer

The intestinal mucus layer separates trillions of commensal and pathogenic microbiota from the host epithelial lining. A mucosal imbalance can lead to Inflammatory Bowel Disease (IBD) or the development of intestinal carcinoma. In the healthy gut, luminal bacteria are separated from the epithelial lining by a mucus layer that is continuously shedding and modified. The majority of intestinal microbiota are associated with the outer mucus layer, but invasive bacteria can breach the mucus layer and cause infection. Epithelial cells that line the intestine express membrane-bound mucins. These transmembrane mucins are innate defense proteins with barrier function and signaling potential that regulate inflammatory pathways and cell proliferation.

The role of transmembrane mucins in the healthy intestine, during invasive infection, inflammatory bowel disease and carcinogenesis.

Transmembrane mucins are instrumental in sensing the intestinal lumen and mounting the appropriate inflammatory response. Our goal is to identify bacteria and mechanisms that trigger activation of transmembrane mucins and determine their contribution to inflammatory responses and carcinogenesis.

Hypothesis on barrier and signaling function of transmembrane mucins. During inflammation, mucins can be activated by shedding of the extracellular domain. Mucin cytoplasmic tails can signal from the plasma membrane or translocate to the nucleus.

We study the molecular mechanisms of transmembrane mucin function by using state-of-the-art molecular techniques, CRISPR/Cas9 DNA technology, protein labeling approaches including sortase technology, confocal microscopy and host-microbe infections assays. This research will contribute to the identification of new targets for anti-inflammatory drugs for the treatment of IBD patients.

Group members