Elucidation of the molecular mechanisms by which in utero environment influences adult onset phenotypes and diseases in humans.

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:
[1]

Waterland et al. (2010) Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. PLoS Genet. 6(12):e1001252.

[2]

Rakyan et al. (2011) Epigenome-wide association studies for common human diseases. Nat Rev Genet. 12(8):529.

[3]

Beyan et al. (2012) Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans. Genome Res. 22(11):2138.

[4]

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.

[5]

Holland et al. (2016) Gene-environment induced epigenetic dynamics at rDNA in the mouse. Science (in press)


Biological Areas:

Development
Genetics

BBSRC Area:

Genes, development and STEM approaches to biology