Phone: 024 765 74523
Office: IBRB 3.02
Warwick Centres and GRPs
Vacancies and Opportunities
For PhD and postdoctoral opportunities, and interest in potential collaborations, please contact me at the above email address.
As embryos develop they become more complex, acquiring progressively more cell types in order to form fully functional tissues and organs. Emergence of new cell types during development is highly coordinated in time and space. This coordination involves the activation and deactivation of specific sets of genes through multiple waves of programming, largely controlled by signals received from neighbouring cells and local tissue environments. Whether genes are activated or deactivated is heavily influenced by regulatory DNA sequences, and whether they are accessible to the relevant cellular machinery. We seek to understand how cues received by cells influences use of different DNA sequences by specialised proteins to activate and deactivate genes, and thus control cell identities.
The Nelson lab studies how cell identities are determined in two distinct contexts. We use zebrafish to investigate how specialised cells known as “endoderm” arise in the early embryo, and go on to make major contributions to the respiratory and gastrointestinal tracts, and associated organs including liver and pancreas. We also use stem cell cultures to investigate how the mouse placenta forms, and produces specialised cells that enhance blood supply to the developing foetus during pregnancy, and perform nutrient and waste exchange between mother and foetus.
Elucidating how programming of different cell types is controlled in zebrafish and mouse has a range of benefits. These include: (1) understanding how such processes likely occur in humans; (2) informing how cells of therapeutic value can be produced in the lab; (3) revealing how errors in gene activation through mutations in DNA can lead to developmental and metabolic defects; and (4) understanding how changes in these fundamental biological processes have driven differences between species during evolution.
Our main long-term goal is to understand how mutations in regulatory DNA sequences contribute to developmental defects and pregnancy complications.
Research: Technical Summary
The overall focus of our group is on gene regulatory control mechanisms underlying cell fate decisions during vertebrate embryogenesis. This is divided into two main areas:
Trophoblast Stem Cell (TSC) differentiation
TSCs are a multipotent cell type of foetal origin, which gives rise to the range of distinct trophoblasts subtypes within the placenta. Different trophoblast subtypes control different aspects of placenta function, such as maternal-foetal exchange, hormone production and expansion of the maternal vasculature to enhance the blood supply to the developing foetus. We culture and study mouse TSCs in the lab to investigate the molecular mechanisms controlling cell fate decisions during trophoblast differentiation using genetic, functional genomics, transcriptomics and proteomics approaches. This will help us to understand how the placenta develops correctly to maintain a healthy pregnancy, and how defects in placenta formation can lead to pregnancy complications such as preeclampsia.
Endoderm specification and differentiation
Endoderm, one of the three primary germ layers in the early vertebrate embryo makes direct contributions to several organs including liver, pancreas, and the digestive and respiratory tracts. A major goal of our research is to understand how gene regulatory networks control the specification of endoderm and its diversification into different endodermal cell types. To address this we use both zebrafish embryos and differentiating mouse embryonic stem cells as model systems, combined with genetic, functional genomic and transcriptomic approaches. Understanding how different endoderm cell types form during development will provide key insights into developmental disorders, and lead to refined regenerative medicine strategies.
For a full list of publications, see WRAP
- Associate Professor, School of Life Sciences, University of Warwick, 2021-present
- Assistant Professor, School of Life Sciences, University of Warwick, 2017-2020
- Postdoctoral studies with Prof. Elizabeth Robertson FRS, Sir William Dunn School of Pathology, University of Oxford, 2012-2017
- Postdoctoral studies with Dr Fiona Wardle, Department of Physiology, Development and Neuroscience, University of Cambridge, and Randall Division of Cell and Molecular Biophysics, King’s College London, 2008-2012
- PhD studies with Dr Andrew Fraser, Wellcome Trust Sanger Institute/University of Cambridge, 2004-2008
- BSc (Hons), Applied Biochemistry, University of Liverpool, 2000-2004
Member of British Society for Developmental Biology, 2009-present
Ad hoc reviewer for multiple journals including: “Development”, “eLife”, “Nature Communications”, “Genome Research”, “Genome Medicine”, “Frontiers in Cell and Developmental Biology” and others.Ad hoc reviewer for multiple funding bodies including: BBSRC, MRC, Leverhulme Trust, Human Frontier Science Programme.