Goblet cells and the mucus barrier in intestinal inflammation

• Applicant: Dr. Aline Azabdaftari
• Subject Area: Pediatric and Adolescent Medicine ; Gastroenterology
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 501883972

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder caused by a dysregulated immune system and breakdown of the epithelial barrier. In IBD, particularly in Ulcerative colitis (UC), goblet cell depletion and defects of the protective epithelial mucus barrier are common findings on histology. Goblet cells are the main producers of mucus, and they can be distinguished in different subtypes. While subtype-specific alterations have been described in UC, it is yet unknown what causes the goblet cell dysfunction and how it affects the mucus barrier.The objectives of this project are to identify the mechanisms of goblet cell dysfunction, and to determine alterations of the mucus barrier function and structure in UC. To achieve this, I will investigate the goblet cell compartment and the mucus barrier in a monogenic disease model of IBD with increased endoplasmic reticulum stress and goblet cell depletion, alongside patients with UC. I will apply single cell RNA sequencing on biopsies and patient-derived colonic organoids together with functional assays to assess goblet cell differentiation, inflammatory states, cell death and endoplasmic reticulum stress pathways. A microfluidic organ-chip system will serve to determine the structure and susceptibility to bacteria in a setting of defective mucus layer. This will advance understanding of the pathophysiology leading to intestinal inflammation and guide novel therapeutical strategies that restore goblet cell and mucus barrier function in the intestine of UC patients.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Dr. Holm Uhlig