Von Willebrand Factor (VWF) plays a pivotal role in blood coagulation. VWF is secreted from endothelial cell Weibel-Palade bodies (WPBs), which is crucial for the response to vascular trauma. Dysfunctional WPB biogenesis and exocytosis are characteristic of bleeding disorders such as Von Willebrand disease. In this project, we aim to identify the organelle trafficking routes responsible for WPB formation and secretion.

This project is a collaboration between the research groups of Dr. Ruben Bierings (Department of Hematology, Erasmus MC, Rotterdam; https://www.hematologyrotterdam.nl/laboratory-research/ruben-bierings) and Prof. dr. Geert van den Bogaart (Department of Molecular Immunology, Faculty of Science and Engineering, University of Groningen (UG); www.membranetrafficking.com).
Two PhD positions are available, one at each institute.

The Erasmus MC candidate will conduct biochemical assays of WPB cargo secretion and optical assays of WPB exocytosis to determine changes in secretory competence and fusion mode due to altered SNARE sorting. Techniques include high content microscopy, proteomics, total internal reflection fluorescence (TIRF) microscopy, shRNA library screenings, and electron microscopy.

The UG candidate will utilize newly developed microscopy methods, including Förster resonance energy transfer-fluorescence lifetime imaging (FRET-FLIM), to map SNARE protein trafficking to WPBs. Techniques include FRET-FLIM microscopy, mammalian cell culturing, CRISPR, and molecular cloning.

The PhD candidates are expected to also spend research time at the other institute.

If you are ready to tackle the molecular cell biology of bleeding disorders, we encourage you to apply for this exciting PhD opportunity at Erasmus MC. You have the following qualifications:

• A university MSc degree in molecular biology, biochemistry, cell biology, biomedical sciences or any other field that has affinity with basic and/or translational research.
• Excellent communication and presentation skills. Fluency in English (oral and written) is a prerequisite.
• Self-motivated, detail-oriented, and adept at both independent and collaborative work.
• Extensive hands-on practical laboratory experience is required, previous experience with mammalian cell biology and advanced microscopy approaches is an advantage.
• Willing to spend research time in Groningen.

• You will receive a temporary position for 4 years. The gross monthly salary is € 3.017,- in the 1st year and increases to € 3.824,- in the 4th year (scale OIO).
• Excellent fringe benefits, such as a 13th month that is already paid out in November and a individual travel expense package.
• Pension insurance with ABP. We take care of approximately 2/3 of the monthly contribution.
• Special benefits, such as a incompany physiotherapist and bicycle repairer. And there is also a gym where you can work on your fitness after work.

Erasmus MC

The Department of Hematology at the Erasmus MC has pioneered innovative methods to understand the mechanisms of hematological disease on a molecular and cellular level. Combination of our patient cohort studies with cutting-edge molecular and cellular technologies on patient cells provides the unprecedented opportunity to perform innovative research on the biological mechanisms of disease and to make discoveries that impact the routine practice of patient care. The Erasmus MC is the largest treatment center for bleeding disorders in the Netherlands and our clinical and basic research revolves around understanding why patients bleed and how to improve their treatment.

In our lab (https://www.hematologyrotterdam.nl/laboratory-research/ruben-bierings) we use in vitro and ex vivo experimental studies on (patient-derived) endothelial cells with the objective to elucidate the mechanisms that regulate secretion of hemostatic proteins, in health and disease.

A PhD training program is part of the agreement and the successful candidate will be enrolled in the Erasmus MC Graduate School (https://www.eur.nl/en/erasmusmc/graduate-school).

For more information about this position, please contact Dr. ir. Ruben Bierings, r.bierings@erasmusmc.nl or g.van.den.bogaart@rug.nl.

If you are keen on this position and would like to apply, please do so by using the application form on our website. Please provide the following documents:

• Motivation letter (max 1 page).
• Up-to-date CV (max 2 pages).
• List of grades for MSc degree.
• Contact details or letters of recommendation of two references.

Screening of applications will start as soon as applications are received and will continue until the position is filled.