SANDPIT: Intracellular mechanisms of lumen formation in angiogenesis

Angiogenesis is a process of fundamental importance in embryonic development, in wound healing and in diseases such as cancer. It involves the growth of new blood vessels, and is controlled by complex pathways with biochemical, genetic, mechanical and environmental dependence. Driven by external stimuli, endothelial cells can migrate into tissue surrounding existing blood vessels to form cords that develop closed loops, which must then develop an internal lumen to allow new blood flow pathways to develop. Lumen formation occurs through a variety of mechanisms. In vitro studies have shown that one such mechanism involves the formation of vacuoles within an endothelial cell: the vacuoles merge with each other and then with the cell membrane to create a channel for blood flow. The present project has two primary aims. First, sections of tissue undergoing vigorous angiogenesis (mouse corpus luteum) will be examined under electron microscopy to investigate the dynamic processes of lumen formation in vivo. This will be a postdoctoral researcher with a mathematical training, to give them exposure to biological techniques and issues. Necessary training will be provided. Second, the researcher will develop simple mathematical models of intracellular vacuolization. The ultrastructural images should provide new insights into the dynamics of lumen formation in vivo; models will help identify the rate at which vacuoles merge. The results of this preliminary project will form the basis of a future more substantial research proposal.