The luminal surface of the small intestine is formed by a near continuous sheet of absorptive epithelial cells called enterocytes. In gut morphogenesis, enterocytes reorganize their apical domain to form a highly polarized actin structure known as the brush border, consisting of an array of finger-like membrane protrusions called microvilli. These actin-based protrusions enlarge the surface area, house transporters and channels required for nutrient uptake, and can release host-defense mechanisms into the intestinal lumen. The molecular players that control the establishment, maintenance, and regeneration of the brush border remain poorly characterized in vivo.
The goal of this project is to gain novel insight into the molecular organization of the apical domain of the intestine of C. elegans using expansion microscopy. Expansion microscopy is a powerful new technology for imaging biological specimens with fine detail by physically making them bigger through an isotropic chemical expansion process.
Objectives of the project include:
Optimize expansion microscopy for imaging in the elegans intestine (starting from protocols developed for human cells by Kapitein).
Localize microvilli, terminal web and intermediate filament network components at <50nm resolution using expansion microscopy. We will initially focus on known components from our own work and that of G. Michaux. Later in the project, we will investigate novel components identified in the projects of DC 1 and 5.
Determine effect of known regulators of apical morphology whose molecular functions remain unknown on ultrastructure of the apical exchange surface of the elegans intestine. Initial experiments will focus on the intermediate filament regulator BBLN-1 (Boxem lab) and newly identified myosins (Michaux lab).
The Boxem and Kapitein groups are part of the Institute of Biodynamics and Biocomplexity at Utrecht University. Utrecht University is a friendly and ambitious university at the heart of an ancient city. We love to welcome new scientists to our city – a thriving cultural hub that is consistently rated as one of the world’s happiest cities.
Position now open for applications (deadline October 15). For more information or to apply, please follow this link.