We are looking for two highly motivated PhD students who will join our research efforts to understand how epithelial cells become polarised, functionally specialise, and function. 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 specialised functions and organise the 3D multicellular body.

The two PhD positions are part of the European PhD Training network SurfEx, funded by the Marie Skłodowska-Curie Actions (EU programme for doctoral education). Both projects use the nematode C. elegans as a model system. Within this animal model, the polarisation 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.

1. PhD position on Nanoscale imaging of the apical exchange surface. 

   The goal of this project is to gain novel insight into the molecular organisation of the apical domain of the intestine of C. elegans using expansion microscopy. Expansion microscopy is a powerful new technology for imaging biological specimens with fine detail by physically making them bigger through an isotropic chemical expansion process.
   
   Objectives of the project include:

   • Optimize expansion microscopy for imaging in the elegans intestine (starting from protocols developed for human cells by the Kapitein lab.
   • Localise microvilli, terminal web and intermediate filament network components at <50nm resolution using expansion microscopy.
   • Determine effect of known regulators of apical morphology whose molecular functions remain unknown on ultrastructure of the apical exchange surface of the elegans intestine. Initial experiments will focus on the intermediate filament regulator BBLN-1 (Boxem lab) and newly identified myosins (Michaux lab). 

2. PhD position on identification and characterisation of terminal web and brush border components in C. elegans. 

   The aim of this project is to identify and characterise novel components involved in the polarisation and specialisation 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 localisation 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.

SurfEx:
SurfEx brings together 8 labs/industrial partners aiming to gain a new understanding of how the apical exchange surface of epithelial cells is formed and functions in health and disease. As one of the 12 doctoral candidates within the SurfEx network, you will have the opportunity to work with leading academics and industrial partners from across Europe, gaining valuable experience in international collaboration and cutting-edge research. You will also benefit from a comprehensive training programme that includes workshops, courses, and secondments, all aimed at enhancing your research and professional skills.

To qualify for this position you cannot have resided or carried out your main activity (work, studies, etc.) in the Netherlands for more than 12 months in the 36 months preceding the recruitment date.

For this function you should have:

• a Master's degree (or equivalent) in Biology, if you are within a few months of completing your MSc degree, we also welcome you to apply! Please indicate in your application letter when you are likely to graduate;
• a strong background in at least one but preferentially two of the following areas: Developmental Biology, Cell Biology, or Molecular Biology;
• a strong interest in performing in vivo studies in elegans;
• proficiency in academic English.

• a full time PhD position for 4 years (the first three years are funded by the Marie Curie Doctoral Networks programme of the European Commission, the fourth year by Utrecht University);
• the opportunity to participate in the education programme of the Graduate School of Life Sciences  and in the Marie Curie PhD training network (SurfEx)
• a full-time gross salary starting at  €2,770 in the first year and increasing to €3,539 in the fourth year (scale P Collective Labour Agreement Dutch Universities (cao));
• 8% holiday bonus and 8.3% end-of-year bonus;
• a pension scheme, partially paid parental leave, and flexible employment conditions based on the Collective Labour Agreement Dutch Universities.

In addition to the employment conditions from the CAO for Dutch Universities, Utrecht University has a number of its own arrangements. These include agreements on professional development, leave arrangements, sports and cultural schemes and you get discounts on software and other IT products. We also give you the opportunity to expand your terms of employment through the Employment Conditions Selection Model. This is how we encourage you to grow.

For more information, please visit working at Utrecht University.

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You will work in the group of Professor Mike Boxem in the Developmental Biology division (Department of Biology). The Boxem group works closely together with the groups of Professor Sander van den Heuvel, Dr Suzan Ruijtenberg, and Dr Martin Harterink, 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.