The apical membrane domain of intestinal epithelial cells constitutes a critical interface between the host and the microbiota. On a molecular scale, bacteria approaching the apical membrane encounter a dense coat of membrane mucins (glycocalyx). Membrane mucins are a conserved but diverse family of glycosylated transmembrane proteins that exhibit tissue-, cell- and context-specific expression profiles in vertebrates. The hallmark molecular signature of membrane mucins is an linear and extended mucin domain that presents a plethora of complex carbohydrate structures to the gut microbiota. The SurfEx project aims to elucidate how membrane mucins with distinct mucin domain sequences and carbohydrate profiles interact with commensal and pathogenic gut bacteria.
Objectives:
Your project will involve
- Development of strategies for introduction of a combinatorial library of recombinant membrane mucins in mammalian cell models
- Employment of membrane mucin libraries to identify specific domain sequences and carbohydrate signatures that dictate host-microbiota interactions
- Designing mucin mimetics to modulate host-microbiota interactions at epithelial cells surfaces
In your studies you will take advantage of mammalian cell lines and mouse models to investigate mucin-bacteria interaction. The project utilizes an advanced genetic toolkit to generate combinatorial libraries and high-resolution microscopy to evaluate mucin-bacteria interplay in vitro, ex vivo and in vivo.
