Research Program

The main scientific objectives of TOP-GUT are to combine the most advanced cell culture technologies with a strong emphasis on training. The individual research projects of DCs are integrated towards the development of a GI model as a product that facilitates the application in drug development and testing, including biologicals and cell therapy. Projects of each DC will run independently and specific findings in one project on understanding the GI model (WP1) can be directly applied to improve the model (WP2) and test translational applications (WP3).


model complexity

Lead by Prof. Hans Wandall
University of Copenhagen (UCPH), Denmark

Photo by Andres Hocke

This WP fills two major gaps in our understanding of the GI tract, one regarding the glyco-profiles and another regarding the immune cell populations. 

In WP1, we will define the compositional and spatial heterogeneity of the immune cell landscape in the tissue and decipher the mucin and glycocode along the GI and PDOs in homeostasis and infection. We will study the impact of specific mucins and glycans for interactions with probiotics or pathogens of the stomach and intestine.

This is a technological WP focusing on increasing complexity in the in vitro models, by the incorporation of PDOs in  perfusable devices, the addition of an immune cell compartment on chip, addition of crypt-villus 3D structure and replicating the intestinal stroma by co-culturing intestinal organoids with stromal fibroblasts in hydrogels with perfusable vessel-like channels. 

In WP2, several DCs will build the complexity of the GI tract tissue including PDO-immune cell co-cultures in complex OoC devices, we will share and compare methods and outcomes and our industry partners will lay an emphasis on standardization and automatization.


Increasing model complexity

Lead by Assist. Prof. Silvia Mihăilă
Universiteit Utrecht (UU), The Netherlands


Moving the models
towards application

Lead by Prof. Celso Reis
Instituto de Investigação e Inovação em Saúde
da Universidade do Porto (i3S), Portugal

This WP approaches the application of PDOs for personalized medicine. We aim toestablish gastric and colon cancer organoids as a model to test the impact of therapeutic interventions with CAR-T cells, engineered probiotic bacteria and drugs, and evaluate the response to therapeutic interventions according to the target protein glycosylation. We will advance the understanding of the ethical and legal regulation of organoid research, identify the roadblocks in implementation and establish ethics and legal guidelines for GI organoids. 

In WP3, on the road to application, we will develop and enhance patient specific treatment assays for gastric and colon cancer and define ethical and regulatory roadblocks.