The vascular system is a complex hierarchical network to provide nutrients and oxygen but also to transmit signals to distant sites during organ development, homeostasis and repair. Within the vasculature the endothelium is the key regulator of vascular tone and homeostasis and it acts both as a barrier to the underlying tissue but also adapts constantly to changes in mechanical forces, biomechanical and biochemical environment cues. More recently it has been shown that mechanical signals are integrated into growth factor signaling at distinct levels affecting the stability of specific signaling molecules. This strongly affects cell fate decisions by altering their differentiation, proliferation and survival. The BMP signal transduction pathway plays a crucial role in the vascular system as shown by its impact in the development of multiple vascular diseases. BMPs bind to and activate a complex of two transmembrane Ser/Thr kinase receptors and induce via discrete spatially localized BMP receptors distinct signaling pathways leading to transcriptional responses or cytoskeletal rearrangements. The BMP pathway offers several points of integrating biomechanical stimuli at the extracellular, cell membrane and cytosolic sites. The molecular details are not well understood yet, but very important in order to develop novel therapeutic intervention strategies.
In this project we will use multiple molecular biology and cell signaling approaches including CRISPR genome editing, quantitative western blot, siRNA knockdown and immunoprecititations to investigate the role of BMP receptors in vascular biology. We will provide newly established methods in cell and tissue imaging and aim to develop with the successful candidate novel bioreactor systems to combine biochemical growth factor signaling and mechanical stimulations in response to modified cell matrices.
This PhD project is part of the doctoral program of the Berlin Brandenburg School for Regenerative Therapies (BSRT). For more information on how to apply, click here.