Understanding early envirnomental influences on human epigenetic programmes

Previous work has focused on identifying loci whose methylation state varies between individuals but shows strong cross-tissue correlation within individuals, suggestive that the methylation marks were established in the pregastrulation embryo. These regions, recognised as sensitive to periconceptional environment- based on seasonality in Gambian cohorts- are enriched for metastable epialleles and regions of parent-of-origin methylation, many of which demark imprinted loci solely in the placenta. In order to understand the mechanisms involved in variation at these environmentally sensitive methylation hotspots, it is crucial to dissect the methylation profiles of different cells within our model tissue; the placenta. The project will involve generating global expression and methylation profiles in placenta samples from the Gambia collected across consecutive rainy-dry seasons and correlating outcomes with prenatal exposures. Once established, nutrition exposures associated with between individual methylation differences will be modelled using a placenta organoid system.