Liggins Institute


Developmental epigenetics

We are investigating the molecular mechanisms through which factors in the early life environment determine an individual’s phenotype, namely adult body type, physiology and health profile. Knowledge from this emerging field of science holds potential benefits for both human health and agriculture.

Overview


Developmental epigenetics is a re-emerging area of science driven by modern advances in technology.

Epigenetics refers to the molecular mechanisms that cause changes in gene expression without direct alteration to the DNA sequence. It includes, for example, DNA methylation, which involves the (potentially reversible) addition of a methyl group to specific DNA sites, and reversible modifications of the histone proteins that package DNA within chromosomes. Collectively, these epigenetic changes can control how actively genes are expressed.

During early life, the environment in which an organism develops influences the activity of genes through modulation of the epigenetic structure of the genome.

Developmental epigenetics explains how the same genetic sequence can be functionally translated selectively in different cells at different times as a result of different environmental influences that occur during development. It explains why children with a comparable genetic heritage can grow up with their own individual phenotype which includes body composition and health risks.

Improving our knowledge of these early life processes will give us the capacity to manipulate parameters, such as nutrition during pregnancy and in the early postnatal period, to influence the activity levels of key metabolic genes.

The developmental epigenetics group brings Liggins scientists together with scientists at New Zealand Crown Research Institute AgResearch on research in developmental epigenetics that is applicable to the health and development of both humans and farm animals.

The team is exploring developmental plasticity, the process through which the environment can have a profound influence on fundamental aspects of early mammalian development. Acting through maternal sensing of environment (particularly nutrition), the physiology of a fetus (human or animal) becomes adapted in expectation of the postnatal environment to be experienced by the newborn. An epigenetic process, developmental plasticity serves to increase postnatal survival and evolutionary success.

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Investigators


Liggins Institute

Professor Peter Gluckman
Dr Allan Sheppard
Dr Sherry Ngo
Dr Zengxiang Pan

AgResearch

Cameron McLean
Kavitha Babu
Stephanie Moloney
Tony Pleasants

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Collaborators


Associates within Liggins Institute

Prof Wayne Cutfield, Associate Professor Mark Vickers, Dr Anna Ponnampalam, Dr Jian Guan

Associates at other organisations

University of Otago: Associate Professor Peter Dearden
University of Southampton (UK): Professor Mark Hanson, Professor Keith Godfrey
Singapore Institute of Clinical Sciences
EpiGen partners
Stem Cell Sciences Inc (USA)

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Current research projects


Nutritional epigenomics

The goal of this research is to understand how the nutritional environment a ewe is exposed to at the time of conception induces epigenetic changes in gene expression in the offspring affecting the lamb’s early growth potential. This knowledge will be used to develop strategies for managing pregnancies that would otherwise be adversely affected by environmental conditions such as drought, leading to poor lamb growth. It will also lead to development of management strategies to optimise growth and tailored to individual flocks and environmental conditions.

Epigenetics of intrauterine growth restriction (IUGR) in humans

In collaboration with the Singapore Institute of Clinical Sciences (SICS) we are analysing epigenetic profiles of a cohort of Singaporean children born with IUGR and developing a molecular profile to characterise ‘low birth weight’ phenotypes.

Adipocyte biology

We are working with Singapore based researchers to investigate both the basic science and clinical aspects of fat cell biology, specifically the epigenetic regulation of fat specification from precursors and the subsequent differentiation of fat cells (adipocytes).

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Research students


We currently have research students based at the Liggins Institute, at AgResearch in Hamilton and at the Singapore Institute of Clinical Sciences.

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Projects available for new research students


We have new projects available for doctoral and non doctoral research students at each of these locations.

Please contact Dr Allan Sheppard for further information.
Email: a.sheppard@auckland.ac.nz

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Approaches, methodologies used in this research


Central to our research is the Sequenom EpiTyper analysis platform. In addition to standard cellular and biochemical techniques, we also employ confocal microscopy, flow cytometry, mass spectrometry and cell culture extensively.

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Publications


McLean C, Wang Z, Babu K, Edwards A, Kasinathan P, Robl J, Sheppard A (2010) Normal development following chromatin transfer correlates with donor cell initial epigenetic state. Anim. Reprod. Sci.118: 388-393.

Hochberg Z, Junien C, Carel J-C, Boileau P, Deal C, Feil R, Fraga M, Constancia M, Le Bouc Y, K Lillycrop, R Scharfmann, Sheppard A, Skinner M, Szyf M, Waterland R, Waxman DJ, Whitelaw E, Ong K and Albertsson-Wikland K (2010) Child Health, Developmental Plasticity, Epigenetics, and Programming. Endocrine Reviews (in press).

Godfrey K, Sheppard A, Gluckman P, McLean C, Lillycrop K, Burdge G, Rodford J, Slater-Jeffries J, Crozier S, Emerald B, Gale C, Cooper C and Hanson M (2010) Epigenetic marks at birth predict body composition and cardiovascular health at 9 years.
PLoS Gen. (under review).

Wake G, Pleasants A, Sheppard A, Vickers M and Gluckman P (2010) The application of a dynamical model of glucose and insulin interaction to explain an observed affect of leptin administration in reversal of developmental programming. J. Theor. Biol. (under review).

Li C, Yang F and Sheppard A (2009) Adult stem cells and mammalian epimorphic regeneration (invited review)
Current Stem Cell Research and Therapy 4(3): 237-251.

Ngo S, Barry JB, Nisbet JC, Prins JB, Whitehead JP. Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes. Mol Cell Endocrinol 2009;302(1):33-40.

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Funding


Foundation for Research Science and Technology (FRST)
Gravida National Centre for Growth and Development (NRCGD)
Commercial contracts via Epi Gen Research Consortium.

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