Within the department of Physiology at Amsterdam UMC, location VUmc, we focus on basic and translational research in the context of cardiovascular disease. In our group, we are particularly interested in the molecular mechanisms that control cell-cell contact between human endothelial cells. These cells line all our blood vessels and are criticial ‘gatekeepers’ that control coagulation and the transport of fluids and immune cells from the circulation to the tissues and vice versa. This is important during inflammation, for example, and since inflammation is at the basis of cardiovascular disease, understanding its underlying mechanisms is key to the future development of effective therapies.

The regulation of cell-cell contact in endothelium is a major research topic in the group for >15 years. Since this cell-cell contact requires the cytoskeleton, we focus on a group of proteins, the Rho-like small GTPases, that are central regulators of the actin cytoskeleton. The GTPase Rac1 is a positive regulator of endothelial cell-cell contact and is therefore an important protein in our studies. Like many other GTPases, Rac1 is activated by binding to GTP. Rac1 itself hydrolyzes GTP to GDP, which leads to its inactivation. However, this enzymatic activity is not very efficient and the cell therefore uses GTPase activating proteins to promote Rac1-mediated GTP hydrolysis which controls the duration of Rac1 signaling. Interestingly however, Rac1.GTP can also be ubiquitinated and degraded by the proteasome. So there are two mechanisms by which Rac1 is inactivated : GTP hydrolysis and degradation, but it is completely unknown how, where and when the cell ‘chooses’ for one pathway over the other. And that is the key research question of this project.

We are looking for a motivated PhD student who has been trained in cell culture and molecular techniques (preferred background in (molecular) biology, biochemistry or cell biology), who is willing to join our research team to work on this NWO-funded project. You will use primary human endothelial cells in combination with biochemical and cell biological techniques, including (super resolution) live-cell confocal microscopy.

Prerequisites are as follows:

• Master of Science degree in Biology, Biomedical Sciences or equivalent;
• significant experience with cell biological and biochemical= techniques;
• a creative and flexible work attitude;
• a team player with excellent communication skills;
• the capacity to work independently.

Fixed-term contract: 4 jaar.

Salary Scale PHD: 2422 tot 3103 euro gross when employed full-time (depending on qualifications and experience).

We offer you the opportunity for development, deepening and broadening, additional training and a place to grow! Working at AUMC means working in an inspiring and professional environment where development is encouraged in every respect.

• The maximum gross monthly salary based on a 36-hour work week is € 3.103,- (scale OIO CAO UMC).
• The base salary does not include holiday pay (8%) and a year-end bonus (8.3%).
• We offer a contract for 4 years after a trial period of 12 months.

For an overview of all our other terms of employment, see our website.

You will work in a team of PhD students and postdocs that all study various aspects of endothelial and vascular biology, such as metabolic disorders, obesity-related vascular dysfunction and aging. In addition, the department has strong research lines in the fields of cardiomyocyte contractility and studies the crosstalk between heart muscle cells and the endothelium. The dept of Physiology is part of the Amsterdam UMC Research Center ‘Amsterdam Cardiovascular Sciences and of the AUMC ‘hartcentrum’. This means that the project is well embedded in department as well as in the larger AUMC research institute.