John B. Gurdon
To reprogram the nucleus of an adult somatic cell back to an early embryonic pattern of gene expression is a first step in creating stem cells for cell replacement. We aim to find a way of reprogramming the nuclei of readily accessible adult cells in order to generate embryos of the same genetic constitution as the adult cell donors. These derived embryonic cells can then be treated with various factors and conditions to make them specialize into different kinds of cell types. This experimental procedure provides, in principle, a way of creating replacement cells of the same genetic constitution as a donor, thereby avoiding the need for immunosuppression. We transplant nuclei from adult mouse or human cells into the growing oocytes of amphibia. The transplanted nuclei do not replicate DNA or divide but switch their pattern of gene expression directly into that characteristic of stem cells, by activating stem cell marker genes such as Oct4 and Nanog. The very large size and great abundance of amphibian oocytes enables us to try to identify the molecules and mechanisms involved in direct nuclear reprogramming. We combine several cell and molecular biological procedures with nuclear transfer to identify molecules involved in nuclear reprogramming. We plan to identify the mouse or human homologs of the Xenopus reprogramming molecules that we identify. We think it may become possible to overexpress these molecules in adult mammalian cells and so to directly initiate or facilitate their rejuvenation to a stem cell status.
Lab MembershipsGurdon Lab (Principal Investigator/Director)
British Xenopus Group (Other)