PhD position (m/f) in Biolology – CD40 in atherosclerosis (Heidelberg, Germany)

The Institute of Physiology and Pathophysiology of Heidelberg University, Division of Cardiovascular Physiology (Prof. Dr. Markus Hecker) offers a

PhD position

to work on the CD40 ligand-receptor dyad and its role in linking innate immunity to haemostasis in the early phase of atherosclerosis.

Cardiovascular diseases are the number 1 killer in industrialised countries. Atherosclerosis in its advanced stage is the underlying cause for many of them, including infarction and stroke. Understanding the initial steps in the formation of atherosclerotic lesions, whose development strongly depends on the recruitment of immune cells and their contribution to inflammatory processes is therefore of paramount importance for the search of novel therapeutic approaches.

We have recently established that depending on the hemodynamic situation at vessel branches and bifurcations endothelial cells tightly control the amount and functionality of the powerful co-stimulatory receptor CD40 on their surface. Moreover, CD40 ligation with CD154 found on activated platelets in both cultured and native endothelial cells promotes the release of von Willebrand factor (vWF), which is deposited primarily as ultra-large vWF (ULVWF) multimers on their surface in the presence of flow. Platelets rapidly adhere to these multimers, become activated and promote the rolling of circulating monocytes along these ULVWF-platelet strings towards the endothelial cell-cell junctions even at fast or turbulent flow.

By combining different genetic mouse models (conditional cell-specific loss of function) with state of the art imaging and protein detection methods, the successful candidate will analyse in detail the relevance of this CD40 ligand-induced ULVWF multimer-platelet string-mediated monocyte recruitment and activation in the most deleterious vascular remodelling process, i.e. atherosclerosis. A central element of this project will be the establishment of a novel ultrasound-based high resolution imaging method along with advanced cell biology techniques, aided by mass spectrometry imaging of single cells, to detect early atherosclerotic plaque formation and characterise the different types of immune cells present in these plaques.

Group and Working Environment:
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 centres of biomedical research in Europe, provides ample opportunity for scientific exchange not only within the university, but with other renowned research institutions as well.

The project is integrated in the Collaborative Research Centre/Transregio 23 funded by the German Research Foundation (DFG), which, in addition to researchers at Heidelberg University, includes groups at the German Cancer Research Centre, the University of Frankfurt, and the Max Planck Institute in Bad Nauheim.

The PhD candidate will receive advanced training in vascular biology through lectures, courses and summer schools offered by the Integrated Research Training Group established within the CRC/TR23.

References:
Wagner AH et al., Blood 2011; 118:3734-3742.
Demicheva E et al., Circ Res 2008;103(5):477-484.
Korff T et al., Circulation 2007; 116:2288-2297.
Wagner AH et al. Arterioscler Thromb Vasc Biol 2004; 24:715-720.

Methods that will be used:
human cultured cells and experimental mouse models, confocal microscopy (including to intravital 2-photon imaging), live cell imaging (including RICM), mass spectrometry imaging, high-resolution ultrasound imaging

Personal Qualifications:
– Master or diploma in biology, biochemistry, or related fields
– Knowledge of light microscopy, cell biology, and animal experimentation techniques or willingness to acquire the necessary skills
– Ability to rapidly familiarize him/herself with new research areas in theory and praxis
– Team-minded, highly motivated and flexible

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.