The fact that the DFG are continuing to fund the only collaborative research centre (SFB, Sonderforschungsbereich) in Germany that is exclusively focused on vascular research underlines the concentrated expertise found in Mannheim and Heidelberg in the field of vascular biology.
Pathological alterations in blood vessels are intimately linked with many human diseases such as diabetes, stroke, myocardial infarction, peripheral arterial obstructive disease, hypertension, rheumatoid arthritis and cancers. Vascular disease directly or indirectly accounts for approximately 70% of all deaths. Despite the high social and economic impart of vascular disease, surprisingly little is known about the molecular and cellular mechanisms that affect the cells of the vessel wall during disease development. Moreover, the functional analysis of the molecular mechanisms that regulate blood vessel formation has in the past concentrated on the characterisation of molecules and signalling pathways that play a role in angiogenesis (the formation of new blood vessels). Investigations in the past mainly focused on vascular endothelial cells. A great deal less is known about the function of other cells involved in vascularisation and remodelling, including endothelial progenitor cells, pericytes and smooth muscle cells, and their interactions. That is why these cells constitute a major focus in the “Vascular Differentiation and Remodelling” Transregio collaborative research centre.
The SFB-TR23, which was established in 2005, comprises 18 research groups at the University of Heidelberg, including groups from the Mannheim and Heidelberg medical faculties, as well as the University of Frankfurt and the German Cancer Research Centre (DKFZ). The SFB-TR23 is the only DFG-funded special research area in Germany to focus on vascular research. In 2009, the DFG decided to continue funding the SFB-TR23 for another funding period of four years, which essentially confirmed the outstanding expertise found at these research institutions in the field of vascular biology.
The new funding period also brought a new SFB spokesperson. Prof. Dr. Karl Plate's (Institute of Neurobiology at the University of Frankfurt) role as SFB spokesperson was taken over by Prof. Dr. Hellmut Augustin, who is head of the Department of Vascular Biology and Tumor Angiogenesis of the Aventis Foundation at the Centre for Biomedicine and Medical Technology (CBTM) at the Mannheim Medical Faculty and head of the Department of Vascular Oncology and Metastasis at the DKFZ (see BIOPRO article of 27th April 2009): "Interaction mechanisms between tumours and blood vessels". Augustin's professorship in the "Joint Research Division Vascular Biology" cooperatively run by the Mannheim Medical Faculty and the DKFZ, guarantees the close networking of all institutions focused on vascular research that participate in the SFB.
The functional and phenotypic regulation of the cells of the vessel wall are being studied by different SFB-TR23 project groups that each have a different focus (see figure): "Mediators and Effectors" (A), "Cellular Responses" (B) and "Cellular and Systemic Interactions" (C). Moreover, there are two central service projects (Z) that support the work groups in specific research issues.
Project Z5, dealt with by the research group led by Dr. Jens Kroll in Augustin’s department at the CBTM in Mannheim, uses the zebrafish (Danio rerio) as model organism to study vascular development and differentiation. Kroll is also scientific managing director of the SFB-TR23.Since zebrafish embryos and larvae are almost completely transparent, they are excellent tools for studying vascular differentiation and remodelling in living organisms in real time. Moreover, it is easy to study zebrafish embryos due to the external fertilisation of the fish eggs. They develop quickly and can be easily manipulated. Further advantages of using zebrafish as model organisms are that they are easy to keep in large numbers and they also have short generation intervals and can thus be rapidly bred in large numbers.
Working with the research group led by the developmental scientist from Freiburg, Prof. Dr. Wolfgang Driever, Kroll and his team have identified a new signalling pathway that can be used to regulate vascular differentiation during zebra fish development. The scientists identified a new molecular switch (ELMO1) that regulates a signal transduction protein (GTPase Rac1) involved in vascular differentiation and were able to show how this switch is activated in vascular cells.
The importance of vascular medicine as one of four research priorities of the Mannheim Medical Faculty is especially emphasised by the DFG-funded “Vascular Medicine” (GRK 880) research training centre. The GRK 880, which is an international research project due to its close strategic cooperation with institutes at the Rijksuniversiteit Groningen (Netherlands), has now entered its third funding period. The research training programme aims to bring together clinical knowledge and basic research in the field of vascular medicine. The third funding period will focus on “vascular damage” that plays a key role in common diseases such as diabetes, cardiovascular diseases and cancer. The research training centre offers doctoral students the opportunity to pursue their work as part of a coordinated research project supervised by several professors and that aims to progress the treatment of such diseases.
Literature:Epting D, Wendik B, Bennewitz K, Dietz CT, Driever W, Kroll J: The Rac1 Regulator ELMO Controls Vascular Morphogenesis in Zebrafish. Circulation Research, publ. May 13, 2010