Epithelial Exchange Surfaces – From organizing principles to novel culture models of the gatekeepers of the body

Project Information

SurfEx

Grant agreement ID: 101119504

DOI

10.3030/101119504

EC signature date 11 July 2023

Start date 1 December 2023

End date 30 November 2027

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 2 723 263,20

Coordinated by

UNIVERSITEIT UTRECHT
Netherlands

Periodic Reporting for period 1 - SurfEx (Epithelial Exchange Surfaces – From organizing principles to novel culture models of the gatekeepers of the body)

Reporting period: 2023-12-01 to 2025-11-30

Summary of the context and overall objectives of the project

Epithelia are sheets of interconnected cells that line the surfaces of our body and organs, such as the intestine, kidney, lung, and skin. They form essential barriers that protect us from harmful substances and microorganisms while allowing the controlled exchange of nutrients, gases, and waste. When epithelial cells fail to function properly, serious diseases can arise. In the intestine, epithelial defects can lead to infections, chronic inflammation, and impaired nutrient absorption, severely affecting quality of life. In the kidney, epithelial dysfunction can result in cyst formation and progressive organ failure.

A defining feature of epithelial cells is their apical surface, which faces the external environment or organ lumen and is responsible for protection and exchange. Despite its central role, the molecular mechanisms that build and maintain this apical exchange surface remain incompletely understood. Improving this knowledge is essential for understanding the origins of epithelial diseases and for identifying new opportunities for therapeutic intervention.

The SurfEx doctoral network addresses this challenge while contributing to key European researcher training goals. The project integrates fundamental biological research with advanced human-relevant experimental systems, including three-dimensional (3D) cell cultures, organoids, and microengineered platforms. By combining complementary model systems and disciplines, SurfEx aims to generate robust knowledge on epithelial function while training doctoral candidates in state-of-the-art, interdisciplinary approaches.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the reporting period, SurfEx has established the experimental and technological foundations needed to address its scientific objectives.

Our initial studies focusing on the organizing principles of the brush border of intestinal epithelial cells have established genetics screening platforms in the fruitfly Drosophila melanogaster, identified candidate components of the brush border (a specialized structure required for efficient nutrient absorption) in the nematode C. elegans, and established methods to study how the brush border regenerates after injury. These early results provide a framework for more detailed mechanistic analyses planned for the next phase of the project.

In parallel, first insights have been obtained into the extracellular protective layers produced by epithelial cells, such as the mucus layer and the glycocalyx. Preliminary findings indicate that specific epithelial components contribute to barrier integrity and influence susceptibility to bacterial interaction. To support these investigations, new experimental platforms and assays have been established that will allow systematic analysis of barrier composition and function in period 2.

A final focus of the first reporting period has been the development and optimization of advanced three-dimensional (3D) epithelial models. These systems incorporate features such as tissue architecture, mechanical cues, and fluid flow that are not accessible in conventional two-dimensional cultures. The successful establishment of these models now enables targeted studies on epithelial metabolism, autophagy, and mechanosensing, which will be pursued in depth during the second half of the project.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

At this mid-term stage, SurfEx has primarily delivered enabling knowledge, tools, and model systems that position the consortium to address questions beyond the current state of the art in epithelial biology. The main scientific and translational impacts of SurfEx are expected to materialize in the second period of the project, as these platforms are applied to dissect disease-relevant mechanisms and host–microbe interactions in detail. Nevertheless, work perform within SurfEx has already contributed to three scientific publications, one identifying the mucin MUC17 as an essential small intestinal glycocalyx component that is disrupted in Crohn's disease, one describing an unexpected link between the arrest of cell division and brush border formation in the C. elegans intestine, and one describing how maturation of human intestinal epithelial cell layers fortifies the apical surface against Salmonella attack.

In addition to scientific progress, SurfEx is already having a positive impact through its structured doctoral training programme. Early-stage researchers are being trained in interdisciplinary methodologies, advanced model systems, and good research and data management practices in line with Open Science goals. This training lays the groundwork for the development of highly skilled researchers who will contribute to European biomedical research and innovation beyond the lifetime of the project.