Grant: Project Grant

Tissues in multicellular organisms are formed by large numbers of cells that are physically and functionally connected with each other. While surrounded by neighbors, individual cells remain the basic units of life and are responsible for a range of autonomous cellular decisions, such as whether to secrete hormones, to change shape, to divide, or to die. To ensure tissue function, many cells must act together as one functional unit, and this requires coordination of individual cells' behavior with the behavior of their neighbors, through communication between them. Despite their fundamental importance for multicellular biology, the molecular mechanisms enabling such communication, and ultimately resulting in collective behavior of cells, have remained incompletely understood. Capitalizing on established and experimentally tractable models of collective movement of cultured endothelial cells and the formation of vascular tubes, the proposed research aims to identify novel mechanisms of intercellular communication. We will use genetic manipulations of cells, automated cell tracking, and advanced imaging technologies for visualizing and manipulating cellular activities in real time. Endothelial cells form a lining at the inner surface of blood vessels and represent a highly functional barrier between the bloodstream and surrounding tissues. This selective barrier enables distribution of nutrients and oxygen to tissues and, when necessary, the passage of immune cells to sites of infection or injury for clearance. Endothelial cells are also involved in the development of a range of vasculature-related diseases and therefore are of central importance for human health. The anticipated results will not only unveil fundamental principles of how cells are organized into tissues, but also identify new targets of future therapies to treat vasculature-related diseases, a major cause of mortality in Canada and worldwide.