Understanding early environmental influences on human epigenetic programmes

MONK_U21DTP1

Our 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. This 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.

We are looking for an enthusiastic and ambitious student to develop and apply NGS expression protocols and targeted imprinted methylation and expression analysis to better understand how environmental exposure influence the placenta methylome and pregnancy outcome. The project is a joint Norwich Research Park venture between the groups of David Monk at the Biomedical Research Centre, University of East Anglia and Iain Macaulay at the Earlham Institute. In addition to the generic skills training that is provided through the UEA/EI PhD BBSRC NRPDTP programme, the student will be supported by an excellent infrastructure and will work closely with experts in the placental biology and (epi)genomics. This diverse and stimulating environment will allow a creative and talented student to develop key skills in preparation for a successful career in research or industry.

References:

Silver MJ, Saffari A, Kessler NJ, Chandak GR, Fall CDH, Issarapu P, Dedaniya A, Betts M, Moore SE, James PT, Monk D and Prentice AM. Environmentally sensitie hotspots in the methylome of the early human embryo. BioRxiv doi: https://doi.org/10.1101/777508.

Monteagudo-Sánchez A, Sánchez-Delgado M, Ramon Hernandez Mora J, Tubío Santamaría N, Gratacó E, Esteller M, López de Heredia M, Nunes V, Choux C, Fauque P, Perez de Nanclares G, Anton L, Elovitz A, Iglesias-Platas I, Monk D. Differences in expression rather than methylation at placenta-specific imprinted loci is associated with Intrauterine Growth Restriction. Clinical Epigenetics. 2019 11: 35.

Sanchez-Delgado M, Court F, Vidal E, Medrano J, Monteagudo-Sánchez A, Martin-Trujillo A, Tayama C, Iglesias-Platas I, Kondova I, Bontrop R, Eugenia Poo-Llanillo M, Marques-Bonet T, Nakabayashin K, Simón C, Monk D. Human oocyte-derived methylation differences persist in the placenta revealing widespread transient imprinting. PLOS Genetics. 2016, 12 (11): e1006427.