Imprinting in health and disease
Lead Research Organisation:
University of Cambridge
Department Name: Anatomy
Abstract
Correct growth of babies in the womb and after birth is of great importance to health and prospects later in life. The particular interactive grouping of investigators on this MRC cooperative, combines basic science (mouse models, cell physiology, molecular genetics) approaches with clinical work (patient cohorts) to work out how a particular class of genes (the imprinted genes) are involved in the control of growth of the baby, the function of and relationship with its placenta, and how mistakes and mutations in these genes can lead to growth and developmental abnormalities and neural disorders. Each of the participating institutes encourages communication of research activities and results to the lay public. This includes proactive and responsive policies for producing press releases and talking to journalists and the media about any research of possible interest to the public. Specific public forums include a Schools Open Science day and participation in National Science Week and talks by scientists about research to school students, adult evening classes and community groups.
Technical Summary
Genomic imprinting is a process that causes genes to be expressed according to their parental origin. This Cooperative Grouping was established in 1999 with the aim of fostering interaction between experimental and clinical studies on genomic imprinting. The key objectives of identifying new imprinted genes, establishing detailed analyses of physiological and developmental pathways of their action in fetal growth, and of identifying imprinting gene defects in the human population, were all achieved. This has put the Cooperative in an excellent position to increase the number of PIs in complementary areas evolving from the existing studies and to tackle a new set of objectives. These are:
(1) the application of critical analysis into growth control from mouse knockout models to normal and aberrant human intrauterine growth,
(2) to explore the action of imprinted signalling pathways in adaptations to early postnatal life,
(3) to explore the action of imprinted genes in brain and behaviour and
(4) to investigate epigenetic mechanisms of imprinted gene expression associated with growth, developmental and behavioural phenotypes.
The new name of the Cooperative, ?Imprinting in Health and Disease? reflects its wider remit while it remains committed to a multidisciplinary approach linking experimental with clinical studies.
(1) the application of critical analysis into growth control from mouse knockout models to normal and aberrant human intrauterine growth,
(2) to explore the action of imprinted signalling pathways in adaptations to early postnatal life,
(3) to explore the action of imprinted genes in brain and behaviour and
(4) to investigate epigenetic mechanisms of imprinted gene expression associated with growth, developmental and behavioural phenotypes.
The new name of the Cooperative, ?Imprinting in Health and Disease? reflects its wider remit while it remains committed to a multidisciplinary approach linking experimental with clinical studies.
Organisations
- University of Cambridge, United Kingdom (Lead Research Organisation)
- University College London, United Kingdom (Collaboration)
- MRC Harwell, United Kingdom (Collaboration)
- Babraham Institute (Collaboration)
- St Jude Children's Hospital (Collaboration)
- University of Birmingham, United Kingdom (Collaboration)
- University of Manchester, Manchester, United Kingdom (Collaboration)
Publications

Ryder E
(2006)
MAMMOT--a set of tools for the design, management and visualization of genomic tiling arrays.
in Bioinformatics (Oxford, England)

Rugg-Gunn PJ
(2007)
Status of genomic imprinting in human embryonic stem cells as revealed by a large cohort of independently derived and maintained lines.
in Human molecular genetics

Charalambous M
(2007)
Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life.
in Current opinion in endocrinology, diabetes, and obesity

Burdon C
(2007)
Oxidative stress and the induction of cyclooxygenase enzymes and apoptosis in the murine placenta.
in Placenta

Coan PM
(2008)
Disproportional effects of Igf2 knockout on placental morphology and diffusional exchange characteristics in the mouse.
in The Journal of physiology

Ogata T
(2008)
Molecular mechanisms regulating phenotypic outcome in paternal and maternal uniparental disomy for chromosome 14.
in Epigenetics

Ellery PM
(2009)
Evidence for transcriptional activity in the syncytiotrophoblast of the human placenta.
in Placenta

Kong A
(2009)
Parental origin of sequence variants associated with complex diseases.
in Nature

Glass JL
(2009)
CG dinucleotide periodicities recognized by the Dnmt3a-Dnmt3L complex are distinctive at retroelements and imprinted domains.
in Mammalian genome : official journal of the International Mammalian Genome Society

Lim AL
(2010)
Genomic imprinting effects in a compromised in utero environment: implications for a healthy pregnancy.
in Seminars in cell & developmental biology

Smallwood SA
(2011)
Dynamic CpG island methylation landscape in oocytes and preimplantation embryos.
in Nature genetics

Williamson CM
(2011)
Uncoupling antisense-mediated silencing and DNA methylation in the imprinted Gnas cluster.
in PLoS genetics
Description | MRC Collaborative Grant |
Amount | £734,199 (GBP) |
Funding ID | G0801156 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2009 |
End | 09/2013 |
Description | MRC Programme Grant |
Amount | £2,400,000 (GBP) |
Funding ID | MR/K011332/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2013 |
End | 12/2017 |
Description | TSB grant |
Amount | £600,000 (GBP) |
Organisation | Innovate UK |
Sector | Public |
Country | United Kingdom |
Start | 01/2010 |
End | 03/2013 |
Description | Cooperative workshops/meetings |
Organisation | Babraham Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | hosted/organised workshops meetings |
Collaborator Contribution | collaborative interactionscollaborative interactionsgeneration of the Epigenomics Facility, site of next generation sequencing facilitiescollaborative interactionscollaborative interactions |
Impact | Too numerous to mention without extensive collation from the other Cooperative Groups involved - University of Cambridge, Babraham Institute, Kings College London, Institute of Child Health London, MRC mammalian genetics unit - Harwell, University of Manchester, University of Birmingham. |
Description | Cooperative workshops/meetings |
Organisation | MRC Harwell |
Department | MRC Mammalian Genetics Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | hosted/organised workshops meetings |
Collaborator Contribution | collaborative interactionscollaborative interactionsgeneration of the Epigenomics Facility, site of next generation sequencing facilitiescollaborative interactionscollaborative interactions |
Impact | Too numerous to mention without extensive collation from the other Cooperative Groups involved - University of Cambridge, Babraham Institute, Kings College London, Institute of Child Health London, MRC mammalian genetics unit - Harwell, University of Manchester, University of Birmingham. |
Description | Cooperative workshops/meetings |
Organisation | University College London |
Department | Institute of Child Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | hosted/organised workshops meetings |
Collaborator Contribution | collaborative interactionscollaborative interactionsgeneration of the Epigenomics Facility, site of next generation sequencing facilitiescollaborative interactionscollaborative interactions |
Impact | Too numerous to mention without extensive collation from the other Cooperative Groups involved - University of Cambridge, Babraham Institute, Kings College London, Institute of Child Health London, MRC mammalian genetics unit - Harwell, University of Manchester, University of Birmingham. |
Description | Cooperative workshops/meetings |
Organisation | University of Birmingham |
Department | College of Medical and Dental Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | hosted/organised workshops meetings |
Collaborator Contribution | collaborative interactionscollaborative interactionsgeneration of the Epigenomics Facility, site of next generation sequencing facilitiescollaborative interactionscollaborative interactions |
Impact | Too numerous to mention without extensive collation from the other Cooperative Groups involved - University of Cambridge, Babraham Institute, Kings College London, Institute of Child Health London, MRC mammalian genetics unit - Harwell, University of Manchester, University of Birmingham. |
Description | Cooperative workshops/meetings |
Organisation | University of Manchester |
Department | School of Medicine Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | hosted/organised workshops meetings |
Collaborator Contribution | collaborative interactionscollaborative interactionsgeneration of the Epigenomics Facility, site of next generation sequencing facilitiescollaborative interactionscollaborative interactions |
Impact | Too numerous to mention without extensive collation from the other Cooperative Groups involved - University of Cambridge, Babraham Institute, Kings College London, Institute of Child Health London, MRC mammalian genetics unit - Harwell, University of Manchester, University of Birmingham. |
Description | Epigenetic stability in human induced pluripotent stem (iPS) cells |
Organisation | St Jude Children's Hospital |
Department | Department of Surgery |
Country | United States |
Sector | Hospitals |
PI Contribution | Initiated iPS cell study |
Collaborator Contribution | additional programme of work |
Impact | additional funding from Technology strategy partnership in collaboration with CellCentric, Sigma, MRC Centre for Regenerative Medicine Cambridge, University College London. Project entitled 'Manufacturing solutions for high value induced pluripotent stem cell products' Total 2.4M pounds |
Start Year | 2008 |
Description | MRC cooperative - extensive collaborations |
Organisation | Babraham Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This cooperative group successfully interacted to generate multiple collaborative projects. |
Collaborator Contribution | too numerous to mention |
Impact | Publications of the Coordinating PI are listed. Others from members of the cooperative group are too numerous to mention |
Description | multiple interactions with schools |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Primary Audience | Schools |
Results and Impact | Lecture to school children and hosted visit by Finnish school children at Cambridge University. Similar activities at Babraham Institute. useful experience for schoolchildren |
Year(s) Of Engagement Activity | 2006 |