Microvillus blunting and regeneration in pathological contexts in vivo
The apical membrane of the intestinal epithelium presents a network of actin-based microvilli, called the brush border, which is essential for food absorption, secretion and interactions with the microbiome. In both SurfEx projects, we propose to molecularly and functionally characterize intestinal microvilli in a living organism, using C. elegans as a model, from normal growth to pathological atrophy and regeneration.
In humans, intestinal microvillus atrophy can be inherited or acquired and is associated with food malabsorption, persistent diarrhoea and a severe morbidity. We propose to identify new therapeutic options to treat microvillus atrophy, whether hereditary or acquired. We recently established several genetic and pathological models mimicking inherited and acquired microvillus atrophy in C. elegans. In this project, we will first characterise microvillus atrophy and natural regeneration in these models, using state-of-the-art genetic tools and live super-resolution microscopy. We will then explore the regeneration of microvilli and compare this process to their normal developmental growth. Finally, we will test a role for the gut microbiome in improving regeneration, in a collaboration with the group of Buck Samuel (Baylor College of Medicine, Houston, USA).