Molecular dissection of the role of ARAP3 in angiogenesis

在胚胎发育过程中，特殊组织形成。例如，需要循环系统来滋养发育中的有机体。这个过程称为血管生成。血管生成在癌症中也很重要，因为新的肿瘤需要血液来滋养。当我们研究一只缺乏ARAP 3的小鼠时，我们发现ARAP 3是一种新的信号蛋白，是血管生成所必需的，并且看到胚胎因为无法形成血管而死亡。我们希望确定为什么ARAP 3是血管生成所必需的，以及它是否可以成为癌症治疗的良好靶点。为此，我们将研究ARAP 3的控制方式以及控制其他细胞蛋白质的方式。我们将分析小鼠胚胎中的血管，这些血管要么缺乏ARAP 3，要么含有微小的变化（突变）。其次，我们将研究缺乏ARAP 3或含有突变ARAP 3蛋白的内皮细胞（形成血管），以了解它们与正常细胞的不同之处。最后，我们将把ARAP 3或其突变体放回内皮细胞，以“拯救”它们。通过这种方式，我们将了解为什么ARAP 3是血管生成所必需的，以及它是否是一个很好的癌症药物靶点。

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.