Projects Offered
Edward Lemke Stamatis Papathanasiou Johannes Mayer_Ageing Johannes Mayer_Dynamics Daniel Sasca Natalia Soshnikova Tim SparwasserLineage-specific epithelial drivers of chronic intestinal inflammation
1 PhD project offered in the IPP summer call Molecular Biomedicine & Ageing
Scientific Background
Crohn’s disease is a chronic inflammatory bowel disease characterized by patchy, segmental inflammation of the intestinal mucosa. While immune dysregulation has long been considered central to disease pathogenesis, increasing evidence suggests that specific epithelial cell populations actively contribute to the initiation and persistence of inflammation.
Intestinal stem cells are not a homogeneous population. Distinct stem cell lineages can give rise to epithelial clones with unique functional properties, including differential responses to inflammatory cues and altered barrier function. Understanding how such lineage-specific epithelial programs interact with immune and stromal signals is essential for deciphering why inflammation persists in discrete regions of the gut.
This PhD project focuses on epithelial lineages derived from distinct intestinal stem cell populations, which display transcriptional features associated with inflammatory signaling and intestinal barrier regulation. The overarching goal is to define how these epithelial lineages contribute to chronic intestinal inflammation and how their interactions with the local tissue environment shape disease progression.
PhD Project: Lineage-specific epithelial drivers of chronic intestinal inflammation
The aim of this PhD project is to elucidate the role of epithelial lineages derived from distinct intestinal stem cell populations in intestinal inflammation and barrier dysfunction, with particular relevance to Crohn’s disease. Using complementary in vivo and ex vivo model systems, the project will investigate:
- How epithelial lineages with distinct stem cell origins respond to inflammatory environments
- How lineage-specific epithelial programs influence immune activation and tissue remodeling
- Whether epithelial barrier properties differ between stem cell–derived lineages during inflammation
- How lineage-specific inflammatory mechanisms observed in model systems translate to human disease
The PhD candidate will work with state-of-the-art approaches in intestinal biology, including advanced mouse models, epithelial organoid systems, flow cytometry, transcriptomic and proteomic profiling, and spatially resolved analyses. A strong emphasis is placed on integrating epithelial biology with immunology and systems-level data analysis.
This interdisciplinary project offers the opportunity to uncover fundamental principles of epithelial lineage behavior in inflammatory disease and may contribute to the identification of novel, epithelial-targeted therapeutic strategies for Crohn’s disease.
If you are interested in this project, please select Soshnikova as your group preference in the IPP application platform.
Publications relevant to this project
Chelakkot C, Ghim J, Ryu SH. (2018) Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med. 50: 1-9. Link
Hoshi N, Schenten D, Nish SA, et al. (2012) MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nat Commun. 3:1120. Link
Howell KJ, Kraiczy J, Nayak KM, et al. (2018) DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome. Gastroenterology. 154:585-598. Link
Kühn R, Löhler J, Rennick D, et al. (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 75: 263-274. Link
Luettig J, Rosenthal R, Barmeyer C, Schulzke JD. (2015) Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation. Tissue Barriers. 3:e977176. Link