Defining the mechanism of c-Myb involvement in the regulation of haemopoietic stem cells

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Blood stem cells provide the constant supply of new blood cells throughout life, and they are also important in disease; for example, their ability to replace a patient?s own cells underpins bone marrow transplantation as a therapy for leukaemia and leukaemia-related diseases, whereas on the other hand, mutated versions of blood stem cells are thought to underlie many leukaemias. The unique properties of stem cells depend largely on their profile of active genes, which in turn is controlled by specialised proteins called transcription factors that act as molecular switches. One such protein that appears to be a key in the activation of genes in blood stem cells is c-Myb. This project aims to investigate how and to what extent c-Myb acts as a switch of gene activation in blood stem cells. The work will be performed using stem cells purified from the bone marrow of mice genetically modified to have altered amounts of c-Myb so as to induce changes in the balance of gene activities that it normally controls. The knowledge gained from this study will help to complete the picture of the network of molecular processes that are crucial for normal blood stem cell function, and will have wider implications for the understanding of stem cells in normal and disease situations and perhaps ultimately for their manipulation in a therapeutic context.