Smith Group Pluripotent stem cell biology Pluripotency is the flexibility of single cells to generate all cell types of the animal. This cellular plasticity is the foundation of mammalian development. In the embryo pluripotency is dynamic and short-lived, but in vitro pluripotent stem cells can be established and multiplied without limit. The most pristine type of pluripotent stem cell exists in a naive state, as found in the pre-implantation embryo. To execute their potential for differentiation, naive cells must gain lineage competence, a process termed formative transition. Knowledge of this process can be applied to optimise preparation of pluripotent stem cells for biomedical applications such as disease modelling or cell therapy. We seek to understand: how potency and competence are encoded in a dynamic regulatory network of signals, transcription factors and chromatin how cells transition between states of competence and how fate decisions are made how the trajectory and regulatory machinery of pluripotency are adapted in different mammals Recent papers: Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee: Cell Stem Cell Propagating pluripotency – The conundrum of self‐renewal – Smith – BioEssays – Wiley Online Library Branching topology of the human embryo transcriptome revealed by Entropy Sort Feature Weighting | Development | The Company of Biologists ERK signalling eliminates Nanog and maintains Oct4 to drive the formative pluripotency transition | Development | The Company of Biologists Further information on the Smith Group: Profile | Living Systems Institute | University of Exeter Postdoc Opportunities Exciting opportunity available for stem cell and molecular developmental biologists motivated by fundamental curiosity with a particular interest in early development and/or cell fate decision-making: Stem cells matching the emergent state of naïve pluripotency in the early embryo have so far been established only from rodents and higher primates. Our goal is to capture naïve pluripotent stem cells from a broad range of mammals and to reveal the core gene regulatory network. In this project signalling environments designed from recent insights will be applied to propagate naïve stem cells generated by network resetting, somatic cell reprogramming, and/or direct derivation from livestock embryos. Multimodal profiling, in vitro differentiation and in vivo chimaera formation will be used to evaluate and validate naïve pluripotency. Bioinformatics and network inference will be supported by computational members of the team. Chimaera studies will be carried out in partnership with our collaborator Ramiro Alberio at the University of Nottingham. The position requires cell culture expertise and working knowledge of signalling biochemistry and genetic manipulation techniques. Salary: from £33,482 to £52,565. For application details click here Informal enquiries to: austin.smith@exeter.ac.uk