Identification and characterization of terminal web and brush border components in C. elegans
Cell polarity – the asymmetric distribution of components and functions within a cell along a directional axis – is a fundamental property of cells that is present across the kingdoms of life. Most cells need to distribute proteins, organelles, and functions along an axis of polarity in order to carry out their specialized functions and organize the 3D multicellular body. The aim of this project is to identify and characterize novel components involved in the polarization and specialization of the apical surface of intestinal epithelial cells.
Objectives of the project include:
Identify components of the terminal web and brush border in elegans using proximity labeling proteomics with baits localised at the microvilli tip, core or base, and the terminal web.
Validation of candidate components. Likely novel components of the apical exchange surface (ranked through bioinformatics approaches) will be endogenously tagged with fluorescent proteins via CRISPR/Cas9, and their subcellular localization will be examined by spinning disc confocal microscopy.
Detailed functional analysis of validated candidates using the advanced genetic toolkit available in elegans, including inducible protein degradation to inactivate candidates in the intestine only and at specific times in development.
In your studies you will use the nematode C. elegans as a model system. Within this animal model, the polarization of cells can be followed with single cell resolution, and polarity regulators can be studied using the advanced genetic toolkit available, including CRISPR/Cas9 genome engineering to generate mutants and inducible degradation variants, to be able to inactivate candidates in specific cells and at specific times in development.
The Boxem group is 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. The Boxem group works closely together with the groups of Prof. Sander van den Heuvel, and Dr. Suzan Ruijtenberg who also primarily use C. elegans as a model system. You will therefore be part of an interdisciplinary and dynamic team of researchers that share many common interests and approaches.