Abstract
The developmental programming hypothesis posits that environmental insults in utero can have a major influence on adult-onset disease and phenotypic outcomes. We are interested in understanding the mechanistic basis of this phenomenon in mammals. In particular, identifying developmental programming-induced molecular perturbations, such as epigenetic marks, and then understanding how these perturbations influence phenotype. The project will be highly inter-disciplinary and will involve novel in vitro assays, followed by translation into a unique long-standing human cohort from the Gambia. The experimental work will be underpinned by bioinformatics/statistical analyses of (epi)genome-scale datasets.
References
- Waterland et al. (2010) Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. PLoS Genet. 6(12):e1001252.
- Rakyan et al. (2011) Epigenome-wide association studies for common human diseases. Nat Rev Genet. 12(8):529.
- Beyan et al. (2012) Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans. Genome Res. 22(11):2138.
- Silver MJ et al. (2015) Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Biol. 16:118.
- Holland et al. (2016) Gene-environment induced epigenetic dynamics at rDNA in the mouse. Science 353(6298):495-8.