Dissecting the alterations in intestinal epithelial cell (IEC) differentiation concomitant with goblet cell hyperplasia upon Giardia duodenalis infection

• Applicant: Dr. Christian Klotz
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549511580

Gastrointestinal tract homeostasis depends on the continuous and strictly regulated self-renewal of the epithelium, which is guaranteed by intestinal stem cells (ISC). Disturbance of the homeostasis by infections or irradiation shows a tremendous capability of intestinal epithelial cell plasticity, but this can also result in enormous damage to the epithelium. We have recently demonstrated that intestinal epithelial cell (IEC)-intrinsic NF-kappaB signaling plays an important role in ISC maintenance and fate decisions. In addition, in a newly established model system using human-derived organoids, we have shown that the gastrointestinal parasite Giardia duodenalis triggered significant alterations in NF-kappaB activity in IECs and mediated goblet cell hyperplasia. Here, we will address the open question of the role of NF-kappaB and concomitant signaling pathways in the alterations of IEC differentiation caused by G. duodenalis infection.

• DFG Programme: Research Grants
• Co-Investigators: Dr. Sebastian Rausch; Dr. Ruth Ingeborg Schmidt-Ullrich