A new era for epithelial biology

We use small model organisms, cell cultures and advanced 3D models to study the organisation and physiology of epithelia, improving our understanding of how the apical exchange surface forms and functions in health and disease.

Epithelia are one of the major tissue types that make up the bodies of multicellular organisms. These tissues are sheets of interconnected cells that form the surfaces of our body and our organs, creating physical barriers that protect us from external dangers and control the exchange of materials with the outside environment. Given the essential roles of epithelia in the human body, defects in their functioning are associated with a broad range of diseases.

At SurfEx, an MSCA Doctoral Network focused on studying the surface of epithelial cells, we unite academic and non-academic partners to develop new insights into the formation and functioning of epithelial tissues in health and disease. The top (apical) side of epithelial cells is responsible for the exchange of materials with the outside environment. The formation of a functional apical exchange surface requires complex rearrangements of the cytoskeleton, the formation of surface features like cilia or microvilli, and correct molecular specialization (proteins and lipids).

We combine research in small model organisms with novel 3D culture models to unravel the molecular mechanisms that establish a functional apical exchange surface.

Our research objectives

We will uncover the molecular principles that organise the apical exchange surface of intestinal epithelial cells under normal conditions and during regeneration after pathological damage.

We will determine how the mucus and glycocalyx barriers secreted by the apical surface of intestinal cells shield the epithelium from gut pathogens while promoting selective transport of nutrients and waste.

We will create realistic 3D culture models to investigate factors controlling intestinal and kidney epithelial functioning that cannot be studied in traditional culture systems, such as mechanical stress and fluid shear.

Work Packages

Our research program

Our project SurfEx has 12 individual research projects, each carried out by one doctoral candidate (DC), that fall under three work packages (WPs).

WP1 | Organizing principles of the brush border of intestinal epithelial cells

This work package combines studies in the small model organisms C. elegans and Drosophila to study the molecular mechanisms that organize the apical exchange surface of the intestinal epithelium under normal conditions, during microvilli regeneration and after pathological damage.

  • Project 1

    Identification and characterization of terminal web and brush border components in C. elegans

  • Project 2

    Nanoscale imaging of the apical exchange surface

  • Project 5

    Microvillus blunting and regeneration in pathological contexts in vivo

  • Project 9

    Functional characterization of novel components of C. elegans microvilli

  • Project 12

    Mechanisms of apical domain formation in the Drosophila intestine

WP2 | Composition and barrier properties of the apical extracellular matrix atop polarized epithelia

The projects involved in this work package aim at identifying the molecular determinants of the apical extracellular matrix (ApECM) barrier across the segments of the intestinal tract, and at uncovering how the ApECM can allow selective transport, but at the same time shield the epithelium against gut pathogens.

  • Project 6

    Real-time studies of ApECM barrier protection against gut bacterial attack

  • Project 7

    Mapping the selective barrier properties of cell-attached and shed glycocalyx in human and mouse intestine

  • Project 8

    Recreating human gut microbiota in intestinal mucus models to study infection dynamics

WP3 | Developing and employing advanced epithelial culture models

This work package will develop 3D organoid models and microfluidic perfusable organ-on-chip systems recreating the physiology of epithelial tissues. With these advanced cultures, the projects involved study how epithelial organs are formed and which processes control and coordinate their formation, as well as investigate the processes and signals relevant to epithelial pathologies.

  • Project 3

    In vitro polarization of the proximal tubule: functional implications in health and disease

  • Project 4

    Mechanics, metabolism, and inflammation in lysosome-rich epithelial cells (LREs) in homeostasis and disease

  • Project 10

    Role of actin branching in in healthy and tumor-derived epithelial cells using human-derived organoids

  • Project 11

    Mechanical, inflammatory, and pharmaceutical regulation of cell polarity and the role of primary cilia in a human kidney-organ chip model