SYMPHOGUT project

Microphysiological systems (MPS) are transforming in vitro modeling by providing unparalleled accuracy in replicating human tissues and organs. These platforms are crucial for understanding inflammatory bowel disease (IBD), which remains incurable and demonstrates significant variability, including sex differences in prevalence and treatment. Hormones, particularly estradiol, play a key role in inflammation and modulation of immune responses and have been shown to influence the onset and progression of IBD. This underscores the urgent need for better in vitro models that can mimic these dynamics and replicate patient-specific features. However, the organoid and MPS fields have been limited to the use of Matrigel, a tumor-derived matrix with undefined and variable composition, compromising reproducibility. To overcome these challenges, we will use fully synthetic, cell-instructive, and tunable matrix systems based on photosensitive PEG-hydrogels. Unlike Matrigel, PEG-based hydrogels provide a highly defined, consistent, and customizable microenvironment. These systems will be used to culture intestinal organoids from diverse donors, including both healthy individuals and IBD patients of various ages and sexes, capturing a wide range of biological variability. We aim to explore immune-microbiome-intestinal interactions and uncover sex- and age-dependent factors in IBD progression. This new class of intestinal MPS will enhance understanding of IBD, develop patient-specific therapies, and revolutionize drug development through more efficient preclinical models.

Funding Agency: BMFTR
Funding Period: July 2026 – June 2031
Funding Amount: €1.93 million

 

ECCO Research Grant

This project aims to elucidate how estrogen influences intestinal barrier integrity, immune responses, and therapeutic outcomes in female patients with inflammatory bowel disease (IBD), using advanced patient-derived colonic organoid models (CPOs). Estrogen regulates colonic permeability through the nuclear estrogen receptors, ERβ and ERα, significantly affecting epithelial and immune function. Although these pathways are increasingly recognized as relevant in female IBD pathophysiology, the specific role of estrogen remains largely unexplored.

Funding Agency: ECCO
Funding Period: April 2026 – March 2027
Funding Amount: €80,000