Molecular dissection of the role of ARAP3 in angiogenesis

点击翻译按钮获取中文摘要

During embryonic development, specialised tissues form. For example, a circulatory system is required to nourish the developing organism. This process is called angiogenesis. Angiogenesis is also important in cancer, where new tumours need to be provided with blood so they can be nourished. We found out that ARAP3, a new signalling protein, is needed for angiogenesis when we studied a mouse that lacked ARAP3 and saw that the embryos died because they couldn’t form blood vessels. We want to establish why ARAP3 is required for angiogenesis, and whether it could be a good target for cancer treatment. For this, we will look at the way in which ARAP3 is controlled and in term controls other cellular proteins. We will analyse vessels in mouse embryos, which either lack ARAP3 or where it contains a small change (mutation). Secondly, we will study endothelial cells (which form blood vessels) lacking ARAP3, or containing the mutant ARAP3 protein, to see how they differ from normal cells. Finally, we will put ARAP3, or its mutants back into endothelial cells, to ‘rescue’ them. In this way we will learn why ARAP3 is required for angiogenesis, and whether it is a good cancer drug target.