The Nutrition Theme of MRC Unit The Gambia has been awarded two major grants to build on their existing epigenetics research which focuses on understanding the impact of maternal nutrition on the offspring epigenome and lifelong health. The first grant of £840,00 awarded by MRC is to follow up the discovery that a mother's diet around the time of conception is associated with changes in her infant's epigenome, specifically DNA methylation marks [1].  These marks have the potential to affect gene expression and hence phenotype.  More recently, research conducted by The Unit has revealed that similar changes occur in a gene called VTRNA2-1, and that these changes are stable over a 10 year period [2].  VTRNA2-1 is a tumour suppressor gene with a role in the regulation of the immune system, suggesting that a mother's diet around the time of conception could have a lasting impact on her child's health.

The MRC grant will enable researchers to probe the effects of changes in VTRNA2-1 methylation on gene expression and the immune system through in vitro studies, and by looking for adverse health outcomes in Gambians with atypical methylation at this gene.  Researchers will also interrogate the epigenomes of Gambian infants at high resolution to look for more widespread effects associated with season of conception, taking advantage of the annual cycle of Gambian dry and rainy seasons to perform a 'natural experiment'.  The study will use existing maternal and infant samples from the MRC-funded ENID study [3].  An important element of the research will be a detailed investigation of circulating maternal nutrients involved in one-carbon metabolism, a pathway fundamental to the laying down of epigenetic marks in the epigenome. Study PI Professor Andrew Prentice who leads the Nutrition Theme said: "Our work is already suggesting that a mother's diet around the time of conception can give rise to long term effects on her offspring's health.  This MRC grant will take us a step closer to our goal of devising nutritional interventions that could have an impact on child health by minimising errors in the fetal epigenome that are laid down at the very start of life." The second grant is for research into epigenetic mechanisms linking maternal pre-conceptional micronutrient supplementation with offspring health in India and The Gambia.  The grant for £925,000 was awarded by the Newton Fund in a joint initiative funded by the MRC, the Indian Department of Biotechnology and the UK Department for International Development.  The study is led by Professor Caroline Fall from the MRC Lifecourse Epidemiology Unit at the University of Southampton, UK, with Co-PIs Dr Giriraj Chandak from the Centre for Cellular and Molecular Biology, Hyderabad, India and Dr Matt Silver from MRC ING.

The Gambian arm of the study will look for DNA methylation changes in 7-8yr children whose mothers took part in the Peri-conceptional Multiple Micronutrient Supplementation Trial in rural Gambia [4]. Significant changes will be correlated with a range of health-related outcomes including changes in body composition, cardio-metabolic risk markers and cognitive function.  A major strength of the study will be the ability to compare findings across Indian and Gambian cohorts. Gambian study Co-PI Dr Matt Silver said: "This study perfectly complements our work looking at the impact of circulating maternal nutrients on the infant epigenome at the time of conception by assessing similar effects arising from maternal micronutrient supplementation.  Taken together these two studies present us with a golden opportunity to unpick the complex interplay of dietary factors responsible for laying down the fetal epigenome.  This knowledge could lead to a deeper understanding of how early life exposures can 'program' the body with a significant effect on life long health and disease".

Dominguez-Salas P, Moore SE, Baker MS, Bergen AW, Cox SE, Dyer RA, Fulford AJ, Guan Y, Laritsky E, Silver MJ, Swan GE, Zeisel SH, Innis SM, Waterland RA, Prentice AM, Hennig BJ (2014). Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun; 29;(5):3746

Silver MJ, Hennig BJ,, Dominguez-Salas P, Kessler NJ, Laritsky E, Baker S, Coarfa C, Hernandez-Vargas H, Castelino J, Routledge MN, Gong YY, Herceg Z, Lee YS, Lee K, Moore SE, Fulford AJ, Prentice AM, Waterland RA (2015). Periconceptional environment affects epigenetic metastability at VTRNA2-1, a non-coding RNA with tumor suppressor activity.  Genome Biology (in press).

Moore SE, Fulford AJ, Darboe MK, Jobarteh ML, Jarjou LM, Prentice AM (2012). A randomized trial to investigate the effects of pre-natal and infant nutritional supplementation on infant immune development in rural Gambia: the ENID trial: Early Nutrition and Immune Development. BMC Pregnancy Childbirth 12, 107.

Gulati R, Bailey R, Prentice AM, Brabin BJ, Owens S (2009). Haematological effects of multimicronutrient supplementation in non-pregnant Gambian women. Eur. J. Clin. Nutr. 63, 970–977.