The regulation of early thymocyte development by morphogen signalling

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T cells are white blood cells that are made in an organ called the thymus. T cells are essential to immunity because they both fight infectious diseases and instruct other types of white blood cell to fight infection. Understanding how T-cells are produced is therefore very important to our understanding of immunity. When developing T-cells divide out-of-control T cell leukaemias and lymphomas arise, so understanding what controls their production will also help us to understand and design treatments for leukaemia. This project will study how molecules called 'Hedgehog' proteins control the production of T cells in the thymus. Hedgehog proteins are molecules that are made by cells and secreted to tell other neighbouring cells to undergo a particular process, such as to divide, die or change into a different type of cell. They do this by controlling which molecules are made in the target cell, and this is determined by which genes are active in that cell. Hedgehog proteins are essential in our embryonic development because they transmit messages to developing organs controlling how the organs form and grow. We have shown that after birth Hedgehog proteins are also important in our immune systems because they allow communication between different cells of the immune system. They also determine how many T-cells are produced in the thymus and they can make developing T-cells divide, or stop dividing. We aim to find out what messages Hedgehog proteins give to developing T-cells in the thymus by finding out which molecules are made and which genes become active when Hedgehog proteins signal to T-cells at different stages of their development.