The PhD student will study the role of cell-derived extracellular vesicles in shaping specific adaptive T cell responses. Chronic inflammatory joint diseases, including rheumatoid arthritis (RA) and spondyloarthritis (SpA) are a major health problem affecting approximately 2% of the human population. The pathogenesis of these progressive diseases is characterized by a dendritic cell (DC)-mediated over-activation of specific effector T helper (Th) cell subsets, especially Th1 and/or Th17 cells. In addition, activated innate immune cells are considered crucial players in the initiation and progression of these disorders (especially in SpA), which is exemplified by the fact that polymorphonuclear neutrophils (PMNs) and mast cells (MCs) are present in high numbers both in the inflamed synovial tissue and in synovial fluid (SF) of patients with RA and SpA. Novel insights identify these MCs and PMNs, primarily regarded as innate immune effector cells, as modulatory cells bridging the innate and adaptive immune systems. An important mechanism via which these innate immune cells may exert their modulatory effect is through intercellular communication by extracellular vesicles (EVs). EVs are submicron vesicular structures that are composed of selected lipids, proteins and nucleic acids, and are released by cells in a regulated fashion. EVs are found in all body fluids and have been shown to act at distant sites in absence of direct cellular interactions. In this project we investigate whether EVs from innate immune cells are involved in chronic inflammatory joint diseases. The anticipated discoveries of novel targets involved in immunomodulation will create new opportunities for the treatment of chronic inflammatory joint diseases and for the identification of biomarkers to monitor disease activity in RA and SpA.

We are looking for a highly motivated researcher with:

• Master of Science degree in Biology, Medical Biology, Medicine, or equivalent
• Significant experience with immunological and cell biological techniques
• A creative and flexible work attitude
• A team player with excellent communication skills
• The capacity to work independently

We offer an ambitious and exciting PhD position combining both fundamental and clinical research. You will initially be offered an employment contract for a period of 1 year at the AMC, with the possibility of extension with another 3 years. You will be employed by AMC Medical Research BV.

The salary is in accordance with the UMC-CAO. PhD students (Onderzoeker in Opleiding) are placed in scale 21, with a fulltime gross salary that ranges from €2266,- to €2903,- and is based on qualifications and experience. For a doctor (Arts-Onderzoeker) it’s scale 10, with a fulltime gross salary that ranges from €2903,- to €4194,- and is based on qualifications and experience.

In addition we offer a vacation allowance of 8% of the gross yearly salary and an end-of-year bonus of 8.3%. As a PhD student you are expected to follow courses provided by the AMC Graduate School and you will be a member of the Amsterdam Infection & Immunity Institute (AI&II).

AMC Medical Research

The AMC is more than just a hospital. It is a world in which patient care, research and education are integrated, and in which people are always central. It is an academic world full of possibilities for talented individuals that are looking for a place where they can excel. Thinking big, daring to dream, cooperating internationally. And never letting yourself be put off by ‘It’s not possible’ or ’It won’t work anyway’. That is the AMC mentality.

In the current project three research groups, Prof.dr. Esther de Jong (Dept. of Experimental Immunology, AMC), Dr. Sander Tas (Dept. of Clinical Immunology & Rheumatology, AMC) and Prof.dr. Marca Wauben (Dept. Biochemistry & Cell Biology, Faculty of Veterinary Medicine, UU) will join forces. The complementary knowledge and technologies of this project team create an unique scientific environment and excellent infrastructure which forms a strong research base for the PhD student who will perform experiments at both locations (AMC and UU). Most of the work will be performed at the AMC but several experiments need to be performed at the University of Utrecht.

Within the Dept. of Experimental Immunology of the AMC both fundamental as well as clinical research is performed with a focus on immunity during infections, but also chronic inflammatory disorders and leukemia. The collaboration with various clinical departments within the AMC, amongst others Rheumatology, results in a high degree of synergy and leads to innovative and high quality research.