Deciphering the systems that control epithelial cell polarity

Summary

The candidate will investigate the control of epithelial polarity as part of the Vici project “Deciphering the systems that control epithelial cell polarity”, funded by the Netherlands Organization for Scientific Research (NWO). The candidate is offered a full-time position for 3 years.


Background

Cell polarity is a fundamental property that is essential in human development and for the functioning of adult tissues. Epithelial cells, the most common polarized cells, depend on polarization into apical and basolateral domains to act as selectively permeable barriers between body compartments and with the outside environment. Loss of polarity in epithelial cells contributes to diseases like polycystic kidney disease and retinal dystrophies. Moreover, epithelial cancers are characterized by loss of cell polarity and epithelial integrity, and many polarity regulators are mutated or deregulated in cancer.

The molecular mechanisms that control the formation and maintenance of distinct polarized domains are still far from understood. We also know little of the causal mechanisms by which deregulation of polarity contributes to tumorigenesis. The research in this Vici project focuses on two questions: i) what is the network of interactions between polarity determinants that maintains polarity in established epithelia, and ii) what are the direct consequences of disrupting cell polarity on epithelial integrity, morphology, and cell fate.

To address these questions, the candidate will combine precisely controlled perturbations of the polarizing system with accurate characterization of the effects of these perturbations on the polarizing machinery and on epithelial organization and cell fate.


Approach

The studies will make use of the nematode C. elegans as a model system, because this animal is ideal for in vivo studies of polarity. Due to its transparency and limited number of cells, polarity can be followed in the context of a developing animal with single cell resolution. The presence of multiple distinct types of epithelia allows the investigation of the polarizing machinery in different contexts. Finally, recent developments in inducible protein degradation and tissue-specific gene knockouts make it possible to inactivate proteins in a time- and tissue-controlled manner, and follow the effects on cell polarity, morphology, and fate over time.

Within the Vici framework, multiple individual projects will be developed with input from the candidates. Technical approaches used include the use of CRISPR/Cas9 to engineer fluorescently tagged polarity regulators, and to engineer proteins that can be inactivated in a time- and tissue-controlled manner, live cell imaging using advanced light microscopy, and the use of RNAseq to investigate the effects of polarity loss on cell fate.


We offer

The candidate is offered a full-time position for 3 years (PhD student). The gross salaryt is € 2220,- per month, increasing to € 2840,- in year 4. The salary is supplemented with a holiday bonus of 8% and an end-of-year bonus of 8,3% per year. In addition, we offer a pension scheme, a partially paid parental leave, and flexible employment conditions.

Requirements

We are looking for highly motivated individuals with a PhD degreee, with experience, or an interest in developmental biology and in working with the model organism C. elegans. He/she communicates easily in English, both verbally and in writing, and is eager to work within a team of enthusiastic researchers. Experience with light microscopy, molecular biology, or bioinformatics is appreciated, but not essential.