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Ros John

Professor Ros John

Director of Research, Professor

School of Biosciences

Email
JohnRM@cardiff.ac.uk
Telephone
+44 29208 70145
Campuses
Sir Martin Evans Building, Room Cardiff School of Biosciences, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, Museum Avenue, Cardiff, CF10 3AX
Comment
Media commentator
Users
Available for postgraduate supervision

Overview

Research overview

My research seek to tackle one of the most challenging and fundamentally important questions in human health which is how to maximise the chances of a healthy and successful pregnancy. Pregnancy-related care costs the NHS some £5.8 billion per year, but only 2.4% of all direct, non-industry health-research funding is spent on pregnancy related research (RAND report, 2020). This identifies pregnancy research as one of the most underfunded areas of research in the UK. Yet this is where human health begins and where we can make the most effective changes to improve the health not only of the mother but also for future generations. My research groups ultilises human cohort data (The Grown in Wales Study) and experimental systems to explore how prenatal adversity, which is estimated to impact more than half of all pregnancies in the UK, compromises fetal growth and maternal mental health, and programs some of the most common and pervasive diseases that impact human populations.

Roles

  • Director of Research
  • Academic Team Leader

Publication

2023

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Articles

Book sections

Research

Summary

The principal interest of my laboratory lies in understanding how epigenetic marks direct mammalian development with a particular focus on in utero processes, and how exposure during critically sensitive windows in development can alter outcomes for both mother and child.

Genomic Imprinting

Genomic imprinting is an epigenetic system, first initiated in the germ line, that directs the allele-specific expression of a small set of developmentally important genes (Figure 1). Imprinted genes function within a myriad of networks to regulate fetal growth, placental development, metabolism and behaviour. The aberrant expression of imprinted genes has been reported in relation to low birth weight, placental dysfunction, metabolic and psychiatric diseases. A goal of our research is to further understand the dosage-related function of imprinted genes in development and disease. We are also investigating factors and lifestyles which may influence the expression of imprinted genes early in life resulting in pregnancy complications, mood disorders and poorer behavioural outcomes for children both in the short term and across the life course.

The placenta

We have demonstrated that certain imprinted genes regulate the size of the endocrine compartment of the placenta and consequently modulate the production of placental hormones (Figure 2). During pregnancy placental hormones flood the maternal circulation to induce the physiological changes required for a successful pregnancy. Placental hormones ensure nutrient availability to ensure appropriate fetal growth. Placental hormones also prime the maternal brain in preparation for mothering the newborn infant. Funded by BBSRC, we are using unique experimental models based on the genetically modified expression of imprinted genes to experimentally show that imprinted genes influence fetal growth and maternal caregiving through the regulation of placental endocrine lineages (Figure 3).

Environmental programming

Imprinted genes are regulated by epigenetic marks that can respond to environmental factors. In addition to exploring the consequences of aberrant imprinted gene expression, funded by BBSRC we are investigating whether specific maternal diets or conditions can influence gene expression in the placenta causing placental endocrine dysfunction (Figure 4) and in the fetus directly influencing development, both of which may be linked to the poorer outcomes for children.

Lifelong health

It is well known that prenatal adversity is associated with poorer outcomes for children including behavioural difficulties and metabolic disorders. Funded by BBSRC and Wellcome Trust, we are exploring the consequences of placental endocrine dysfunction on offspring outcomes focusing on offspring behaviour (Figure 4).

Clinical engagement

The imprinted genes we are studying regulate placental development, fetal growth and maternal adaptations to pregnancy via the regulation of placental signalling. The aberrant expression of imprinted genes is common in a number of human disorders of pregnancy including low birth weight, gestational diabetes and preeclampsia. Our recent work suggests that aberrant imprinting may also have relevance to maternal mood disorders programmed by placental dysfunction. Funded by MRC, we initiated “The Grown in Wales” Study (Figure 5) to collect of data and biological samples including placenta from women delivering locally at University Hospital Wales to integrate the knowledge gained from our experimental models with studies on human samples. We are also assessing the development and behaviour of the children from this study in “The Grown in Wales Infant Study” funded by The Waterloo Foundation. Our work will promote the optimal interpretation of clinical data with a longer-term goal of improving diagnostic performance and the identification of possible therapeutic targets for treatment.

Clinical study

“The Grown in Wales Study: Developing and placentomic tool for characterising atypical pregnancies and predicting outcomes.”

REC reference number 15/WA/0004; IRAS project ID 166243; UKCRN ID 18894

Current grant support

Active grants as lead applicant

  • BBSRC (2021-24) Imprinted genes as master regulators of placental hormones.
  • BBSRC (2021-24) Prenatal adversity and the intergenerational transmission of atypical maternal caregiving.
  • TWF (2021-22) Examining whether depression in pregnancy impacts omega-3/6 nutrition and placental transfer increasing the risk of neurodevelopmental disorders

Active grants as co-applicant

  • Leverhulme trust (2021-24) The contribution of maternally expressed imprinted genes to parental behaviour.
  • Foundation for Prader-Willi Research (2020-21) The role of the placenta in PWS: mapping the expression of PWS genes
  • Wellcome Trust Neuroscience DTG “A system level approach to identify and validate imprinted genes involved in parental care” (2019-2022)

External Collaborators

Amanda Fisher (MRC London Institute of Medical Sciences, Imperial College, London)

Takahiro Arima (Tokoyu University, Japan)

Meeting organization

Annual Mammalian Genes, Development and Disease meeting (funded by The Genetics Society)

(Rotates between Cardiff, Bath, Bristol and Exeter)

"Genetics of Reproduction" Sponsored by Genetics Society, this meeting will take place at Royal Society London 18/11/22.

Affiliated staff 

Bridget Allen

Samantha Garay

Alice Chibnall

Ekaterina Lysikova

Ryan Sixtus

Mariia Malinoshevska

Postgraduate research students

As principle supervisor

Alice Chibnall

As second supervisor

Matt Higgs (Wellcome Trust Neuroscience DTP PhD)

Cindy Ikie (BIOSI PhD)

Elnur Aliyev

    Links

    https://www.cardiff.ac.uk/biosciences/research/projects/grown-in-wales

    Podcast from Oct 7th 2021

    https://geneticsunzipped.com/blog/2021/10/7/science-genetics-placenta-mother-baby

    Teaching

    Teaching

    BI2332 Concepts of Disease: Epigenetics and Underlying Principles

    BI3351 Contemporary Topics in Disease: Mouse models of imprinting

    BI3001 Biosciences Final Year Project.

    BI3008 Integrated Masters Biomedical Group Project

    BI4001 Integrated Masters Biomedical Individual Projects

    BIT002 MRes Research Techniques in Bioscience: Research seminar

    Biography

    Rosalind M John is Professor of Developmental Epigenetics and Director of Research for the School of Biosciences at Cardiff University. She received her PhD from Imperial College, University of London and trained at University of San Francisco California (UCSF) and Stanford, USA, and Cambridge University. She has a >20 year track record in the epigenetics of fetal and placental development using animal models to study the relevance of genomic imprinting, and how gene dosage may be influenced by environmental factors mediating short and life long phenotypic outcomes. She is an expert in the generation of BAC transgenic mice (Phlda2, Cdkn1c and Ascl2) and the use of loss-of-function models (Cdkn1c, Phlda2 and Peg3) to gain insight in the relevance of controlled gene dosage. Her group have reported phenotypes affecting fetal growth, placental development, metabolism, adult behaviour and, most recently, maternal behaviour in response to placental endocrine dysfunction. Professor John set up the Grown in Wales Study and the Grown in Wales Infant study to translate her findings from experimental models to humans with relevance to low birth weight babies, maternal mood disorders and neurodevelopmental disorders in children. Professor John’s group is funded by MRC, BBSRC, Wellcome, The Waterloo Foundation and the Welsh Government. Professor John serves on the MRC PSMB and UKRI FLF panels. 

    Professional memberships

    • The Genetics Society;
    • British Society of Developmental Biology;
    • International Society for Developmental Origins of Health and Disease;
    • International Federation Placenta Associations;
    • European Placenta Group;
    • ESRC InteSTELA network;
    • GeCIPs (Genomics England Clinical Interpretation Partnerships) subdomain Imprinting Disorders: Epigenomics, Aetiology and Stratification, or IDEAS);

    Committees and reviewing

    • UKRI Future Leader fellowships Sift Panel Round 7 2023 - 
    • MRC National Mouse Genetics Network scientific advisory board, Chair (2023- )
    • MRC Population and Systems Medicine Board 2021 -
    • Royal Society Biological Awards Search Panel 2021 -
    • Genetics Society Ordinary Committee Member 2021 -(Cell and Developmental Genetics )
    • Speciality Chief Editor for Frontiers in Cell and Developmental Biology: Developmental Epigenetics (2019-2023)
    • UKRI GCRF Health and Context Panel (2019-20)
    • UKRI Future Leaders Fellowships Interview Panel Round 2 (2019)
    • MRC Expert Review Panel for UK NRP Collaborative Awards (2019).
    • BBSRC Expert Review Panel A (2011-2017)

    Supervisions

    There are many opportunities to study for a PhD in my group:

    If you are interested in prenatal adversity, fetal programming, maternal behaviour and/or genomic imprinting AND have access to your own funding or opportunities to apply for funding with a supportive supervisor, please email me to make enquiries: JohnRM@cardiff.ac.uk

    For example, I am principal investigator for two human pregnancy cohorts

    The Welsh Fetal Growth Restriction Cohort - focused on fetal growth restriction and low birth weight

    The Grown in Wales Study - focused on maternal depression and anxiety

    We also have follow up data for the Grown in Wales Infant Study currently aged 4 years.

    PhD students can use these cohorts to study the relationship between specific maternal lifestyles, placental gene expression and outcomes for children with particular relevance to fetal growth restriction and infant neurodevelopment.

    My group also work with experimental murine models of adversity which provide an opportunity for students to undertake research testing causal and effect relationship.

    In addition to these in vivo models, we have tissue culture models where stem cells can be manipulated in culture to examine how this impacts their developmental potential.

    Lots of possibilities for a flexible project to suit your interests!