Kliniken & Institute … Institute Humangenetik Forschung Abt. Molekulare… Genetics of… Intestinal Cell models …

INTESTINAL CELL MODELS

The regulation of intestinal homeostasis is complex and many gastrointestinal diseases are based on a disordered enteric nervous system (ENS) as well as an overshooting of the immune system, which is caused by a disturbed intestinal barrier function (leaky gut). Data indicate that the individual genetic background, acting in concert with a certain gut microbiome, can impair intestinal barrier function, modify the nervous and immune systems and further impact homeostasis. This may contribute to various gastrointestinal and extra-intestinal disorders ranging from Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD) to neurodevelopmental and neurological conditions and cancer.

We aim to investigate underlying disorders of the ENS, the immune and gut barrier function using complementary research approaches. In the long term, we plan to generate patient-specific 3D organoids consisting of intestinal epithelium, immune and neural cells, in which individual organ function can be mimicked.

Our approach has the potential to recapitulate organ development on the one hand, and pathomechanistic changes on the other. The complementary analysis of compartment-specific regulation of gene and protein expression will contribute to a better understanding of pathogenic processes in intestinal diseases. It will also advance the development of new diagnostic procedures and ultimately foster alternative therapeutic approaches.

In order to better understand changes in epithelial barrier and enteric neuronal function we have established respective in vitro models:

  • Epithelial barrier model
  • Enteric nervous system in a dish
  • Human and murine enteric progenitor cell models (Schmitteckert et al., 2019)

The cell models may be manipulated by certain pharmacological compounds, miRNAs/siRNAs as well as genome editing to get an idea about the functional relevance of candidate genes in respective readouts, as barrier function, ENS development and function (proliferation capacity, apoptosis, migration, differentiation capacity, etc.). This will be complemented by exposition studies applying relevant triggers in the pathogenesis of neurogastroenterologic disorders like stress and inflammation.

Last not least, we have an interest in plant extracts having the potential to counteract gastrointestinal disorders, and for which the molecular mechanisms of action are poorly understood. Therefore, we are engaged in the graduate school Train4CIM.

In order to further push the development of our intestinal in vitro models we are partner of the 3R Network Baden-Württemberg with a project aiming to dissect enteric neuropathies and implementing the Interdisciplinary Center for Gut Health Research .

FURTHER INFORMATION

www.izdg.de

Train4CIM

3R Center Tübingen

Funding bodies

Else Kröner Fresenius Stiftung

Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg

Bayer Steigerwald