Living Systems Institute

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 propagated without limit. The most primitive type of pluripotent stem cell exists in a naive  state, as in the pre-implantation embryo. To execute their potential for differentiation, naive cells must gain lineage competence, a process termed formative transition. We seek to understand:

  1. how potency and competence are encoded in a dynamic regulatory network of signals, transcription factors and chromatin
  2. how cells transition between states of competence and how fate decisions are made
  3. how the trajectory and regulatory machinery of pluripotency is adapted in different mammals

Current preprints:

Postdoc Opportunities

We currently have an opening for a postdoctoral research fellow to develop and lead a programme of computational and bioinformatics research. You will delineate developmental trajectories, infer gene regulatory networks and dynamics, and model cell fate transition paths in embryos and stem cell-derived embryoids.

You will work mainly with single cell next generation sequencing data from stem cell self-renewal, differentiation and perturbation studies and from natural and model embryos. The project will include comparative analyses between human, non-human primates and other mammals. You will create and implement algorithms, analysis methods and visualisation tools for interrogation of transcriptomic and multimodal ‘omics datasets. You will generate mathematical and/or computational models of the pluripotency gene regulatory network and of cell fate transitions that will iteratively inform experimental investigation.

You will have the opportunity to develop your own research projects and to supervise project students. In addition, you will collaborate with wet lab researchers in the group in the design and analysis of ‘omics studies and will have the opportunity to perform your own experiments if appropriate.

Prior knowledge in stem cell or developmental biology is not necessary, but experience in working closely with experimental researchers is essential.

The post is available immediately and funded until 31 April, 2027. For further details and to apply: Click here

Postdoc opportunities are also 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:

Post 1: Naïve pluripotent stem cells have to date been established only from rodents and primates. Our goal is to design signalling environments for capturing naïve pluripotent stem cells from livestock and other mammals, including marsupials. Approaches will include pluripotency network resetting and somatic cell reprogramming, as well as direct derivations from livestock embryos. This post requires cell culture aptitude, experience with genetic manipulations, and knowledge of developmental signalling.

Post 2: Mouse and human naïve pluripotent stem cells have overlapping but distinct gene regulatory networks and exhibit different direct lineage potencies. Our goal is to uncover the core gene regulatory network shared across mammalian species. Approaches will include genetic perturbations, transcriptome and chromatin analyses, and network inference. This post requires advanced skills in molecular cell genetics, ability to use basic sequencing analysis pipelines, and an interest in molecular networks.

Both posts are available immediately and funded until June 2026. For further details and to apply: Click here.

Informal enquiries to:

Further information on the Smith Group: Profile | Living Systems Institute | University of Exeter

PhD Opportunities

We currently have no funded PhD positions available.