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

血液干细胞在整个生命过程中提供新血细胞的持续供应，它们在疾病中也很重要;例如，它们取代病人的能力？人类自身的造血干细胞是骨髓移植治疗白血病和白血病相关疾病的基础，而另一方面，突变的造血干细胞被认为是许多白血病的基础。干细胞的独特性质在很大程度上取决于它们的活性基因谱，而活性基因谱又由称为转录因子的专门蛋白质控制，这些转录因子充当分子开关。其中一种蛋白质似乎是造血干细胞中基因激活的关键，它就是c-Myb。该项目旨在研究c-Myb如何以及在多大程度上作为造血干细胞中基因激活的开关。这项工作将使用从小鼠骨髓中纯化的干细胞进行，这些干细胞经过基因修饰，改变了c-Myb的含量，从而诱导其通常控制的基因活性平衡发生变化。从这项研究中获得的知识将有助于完成对正常造血干细胞功能至关重要的分子过程网络的图片，并将对正常和疾病情况下的干细胞的理解产生更广泛的影响，并可能最终在治疗背景下对其进行操作。

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.