GUTPOLAR SIGNED

Project "GUTPOLAR" data sheet

The following table provides information about the project.

 Partnership

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 Project objective

The GUTPOLAR project aims at sustainably reintegrating an Experience Researcher (ER) who will acquire the necessary knowledge and skills to reinforce European research on rare malabsorption diseases. Food absorption relies on the strong polarity of intestinal epithelial cells and the array of microvilli forming a brush border (BB) at their luminal (apical) pole. Some rare genetic malabsorption disorders, characterized by mispolarized PAR polarity modules and BB structural proteins, are caused by mutations in genes coding for membrane traffic factors (i.e. Myo5B in microvillus inclusion disease/MVID). Despite this functional link, little is known about the genetic, physical and functional interactions between membrane traffic, polarity and BB components in vivo and how they control intestinal absorption. The ER uncovered a new role of the V0 sector of the V-ATPase, a complex that controls membrane traffic through organelle acidification, in both polarity and BB components apical polarity maintenance in C. elegans intestine. Most interestingly, V0-ATPase depletion in C. elegans recapitulates the cellular phenotypes observed in patients with MVID, making this complex a very exciting candidate which mechanism, genetic partners and mammalian function need to be characterized. To this end, the ER will first use genetics and super-resolution imaging to study the trafficking routes and the molecular mechanisms controlled by the V0-ATPase in vivo in C. elegans intestine. Then, he will implement mouse intestinal organoids (thanks to a secondment in H. Farin’s lab, Frankfurt, Germany) and use this model to study the conservation of these mechanisms in mammals. Overall, the GUTPOLAR action will allow to describe evolutionary conserved pathways of polarity maintenance and identify some of the mechanisms leading to absorption disorders that may provide the medical community with new therapeutic targets.

 Publications