The role of hemodynamic loading on the link between vimentin and Notch signaling

Description

Notch signalling is a direct cell-cell communication pathway that plays a key role in cardiovascular development. Specific removal of different Notch receptors and ligands has shown that they are essential for the formation of a mature vasculature. Mutations in Notch related proteins can lead to different cardiovascular diseases like CADASIL, Alagille syndrome or calcific aortic valve disease. 

Our group is interested in the role of Notch signalling in vascular organization with a specific focus on mechanobiology. To understand this relationship, we study endothelial cells exposed to shear stress, smooth muscle cells exposed stretch or the interaction between these cell types in response to mechanics. Furthermore, we have found that vimentin, one of the components of the cytoskeleton and family of the intermediate filaments, is interrelated with Notch signalling. However, these studies are still inconclusive and do not give mechanistic insights. The goal in this project is to investigate the role of hemodynamic loading on our previously identified link between vimentin and notch signaling in vascular cells.

In short, the aim of the project is to create vimentin knock out vascular cells to study the relation between vimentin, Notch signalling and cellular mechanics by using the IBIDI and/or Flexcell system. One of the methods to study the role of a protein is silencing through RNA interference. Techniques that can be used are western blots, qPCR and fluorescence microscopy.