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PhD Position in Vascular Biology : Heidelberg, Germany
The Institute of Physiology and Pathophysiology of Heidelberg University, Division of Cardiovascular Physiology (Prof. Dr. Markus Hecker) offers a
Ph.D. position
to work on von Willebrand factor-mediated monocyte extravasation and macrophage polarisation in arteriogenesis.
Vascular remodelling strongly depends on cells of the innate immune system, namely macrophages and monocytes as their precursors. Understanding the crosstalk between the endothelium and these immune cells, and the signaling pathways affecting their attachment, migration and differentiation in particular, may eventually enable us to influence both pathophysiological remodelling processes such as atherosclerosis, and favorable ones like arteriogenesis.
We have established that the interaction between the cell surface molecules CD154 on platelets and the endothelial cell surface receptor CD40, which is tightly controlled by the hemodynamic situation, promotes the release of von Willebrand factor (vWF) stored in specialized secretory vesicles as ultra-large vWF multimers on the endothelial surface. Platelets rapidly adhere to these multimers and turn positive for P-selectin, a marker of cell activation. P-selectin is required for capturing circulating monocytes, allowing their attachment to and subsequent rolling on the luminal vessel wall even under conditions of high blood flow. In addition, stimulation of endothelial cells by binding of CD154 evokes expression of the ligand itself on their surface, setting off a chain of events that govern subsequent monocyte behavior and differentiation.
Clinical data showed that elevated CD154 levels are associated with a high risk of cardiovascular events. Thus, this medically highly relevant project focuses on the interaction of the various components (vWR, CD40 and CD154) in leukocyte recruitment, their transmigration through the endothelial layer and their differentiation into pro-inflammatory macrophages in arteriogenesis. Changes in the synthetic profile of the endothelial cells will also be analyzed to assess the complex changes associated with it, e.g. in intracellular pathways or cytokine formation and release. Another central element of the work program is the establishment of an advanced imaging system for in vivo analyses that includes several months of training with our collaborators in Munich, Germany, as well as a stay with our industrial project partner in Aarhus, Denmark.
References:
Korff T et al., Circulation 2007;116(20):2288-2297.
Wagner AH et al., Blood 2011;118(13):3734-3742.
Wagner AH. Arterioscler Thromb Vasc Biol 2004;24(4):715-720.
Demicheva E et al., Circ Res 2008;103(5):477-484.
Program and Working Environment
You will be integrated in the training program offered by the Marie Curie Initial Training Network “SmArteR”, a major European research and training consortium focused on vascular biology, which includes topical symposia, workshops and summer schools held at different locations.
Our international group consists of 6 principal investigators, 5 postdocs and about 20 PhD and MD students. Heidelberg, home to Germany’s oldest university and one of the premier centers of biomedical research in Europe, provides ample opportunity for scientific exchange not only within the university, but with other renowned research institutions as well.
Methods that will be used:
Multiphoton-based life cell imaging, primary cell culture, animal models, protein biochemistry, immunohistochemistry
Personal qualifications:
• Must not have spent more than 12 months in Germany in the last three years (though no restrictions on citizenship apply)
• Master or diploma in biology, biochemistry or related fields
• Knowledge of microscopical, cell biological, and animal experimentation techniques or willingness to acquire the necessary skills
• Team-minded and flexible
• Ability to rapidly familiarize him/herself with new research areas in theory and praxis
The position is funded for three years and comes with a yearly living allowance in accordance with the Marie Curie Actions Financial Guidelines specified by the European Commission.
The successful candidates will be enrolled in the Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS) of Heidelberg University, which provides an educational framework for young graduate students, both with a bioscience and with a medical background.
Please submit your application via the HBIGS website (http://www.hbigs.uni-heidelberg.de/main_application.html) by March 12 at the latest.
Project no.: Hecker_SmArteR02 …
Job details
Employer:Institute of Physiology and Pathophysiology, Heidelberg University
Website:http://www.medizinische-fakul...
Location:Im Neuenheimer Feld 326, Heidelberg, Baden-Württemberg, Germany
Expires:March 12, 2014
Job type:PhD Studentship
Salary:Unspecified
Qualifications:Postgraduate - Master's degree
Employment type:Temporary
Job hours:Full-time