Programming blood stem cells during embryonic development

We are studying the embryonic signals and nuclear responses involved in the programming of blood stem cells during development. An understanding of the mechanism by which these cells are prevented from differentiating will serve as a paradigm for stem cells in general and facilitate manipulation of these important cells for regenerative medicine. Their genesis in the embryo begins with the formation of cells with blood and endothelial potential in the lateral plate mesoderm which differentiate as arterial endothelium before an epithelial to haematopoietic transition takes place in the floor of the dorsal aorta. We and others have identified many of the signals driving this process and the responding transcription factors that establish the regulatory networks in the nucleus, and we are beginning to model the process. The student will be involved in the manipulation of these pathways in either Xenopus or zebrafish models. In addition to stem cell ontogeny, we have begun to investigate the decisions taken by the stem cells as they migrate to their final resting place. In particular, we are interested in where and how they expand, a property of immense value in the clinic.

The student will become expert in the handling of Xenopus and zebrafish embryos, including temporal and spatial perturbation of gene function, expression profiling in situ and in extracted RNA, generation and use of transgenic lines, cell tracking using fluorescent transgenic lines, cell and protein purification using fluorescent or affinity tags and a broad range of molecular biological techniques including DNA manipulation. The student will also leave the lab with a deep understanding of developmental biology and of haematopoiesis, with a particular emphasis on the development of stem cells. Along the way a knowledge of vasculogenesis and angiogenesis will be obtained.