The models of Pharmacology

SurfEx, TOP GUT, STOP SPREAD BAD BUGS, ORGESTRA

The Pharmacology division of UIPS will collaborate in four Innovative Training Networks (ITNs). The prestigious ITNs are funded by the EU to bring together universities and train a new generation of researchers. This success of the pharmacology is in a large part attributed to their access to model systems, which ultimately will replace animal models and which have more predictive power for the effect in humans (which is the aim of pharmacology). Interestingly, all networks will study gut biology in health and disease.

SurfEx consortium merges basic and translational research to unravel the complexities of epithelial tissues. Epithelia, crucial for bodily functions, safeguard against diseases. Our project investigates the intricate link between cellular polarization and functional outcomes in renal tubular epithelial cells.  The research involves genetically modifying cells, studying downstream pathways, exploring substrate influences on tubule formation, and examining recovery post-injury. Advanced methodologies, including 3D cell culturing and microfluidics, will be utilized to unravel the complex relationship between cellular polarization and functional outcomes in renal epithelial cells.

Researcher: Silvia Mihăilă

TOP-GUT an interdisciplinary training initiative, focuses on innovative preclinical models for personalized medicine. Our project pioneers a '3D gut chip' by incorporating a biomimetic stroma-mimicking system into a microfluidic device, aiming to reproduce crypt-villus features and assess absorption and biotransformation in dynamic conditions. The anticipated outcome is a perfusable chip replicating physiological functions that will allow the analysis of the interplay between topography-shear stress and the absorption and biotransformation profiles of gut-derived metabolites.

Researcher: Silvia Mihăilă

STOP SPREAD BAD BUGS is a consortium built to combat the alarming problem of global antimicrobial resistance. We will establish knowledge and expertise on carbohydrate and protein structures for the discovery of antibiotic alternatives, while characterizing the underlying mechanism of existing compounds for treatment of microbial infections. By using an in vitro infection (E. coli) model with intestinal epithelial cells co-cultured with commensal bacteria, compound efficacy will be determined during pathogen-gut interactions in a pre-clinical setting. Moreover, we will explore whether the novel antimicrobials exhibit anti-infective effects on pathogenic bacteria and hence support the immune system and “healthy” diversity of the microbiota in in vivo infection models. State-of-the-art imaging tools will be applied to track the bacteria and novel compounds in these test systems. The knowledge and tools within this consortium will lead to novel, long-term, antimicrobial strategies to fight against global multi-drug resistance in humans and animals.

Researcher: Saskia Braber

The objective of the project funded through ORGESTRA is to develop gene based therapeutic approaches for cystinosis and cystic fibrosis in advanced organoid based models. Using gene editing (CRISPR-Cas), viral vectors and mRNA based therapeutics we aim to restore gene function in kidney and gut organoids. Different assays will be used to evaluate disease genotypes for either cystinosis and cystic fibrosis and to assess efficacy and safety of the different therapies. Using this approach, we also aim to improve delivery to the kidneys, which is currently a bottleneck in gene based therapies for genetic kidney diseases.

Researchers: Manoe Janssen, Anne Metje van Genderen. This project is coordinated by Roos Masereeuw (coordination)