Gestational dynamics of cell-type specific epigenetic signatures in the placenta

MONK_U21DTP2

Within all tissues, cells differ in the way their genomes are regulated to active genes. This the basis of epigenetic regulation. Despite all cells of an individual having identical DNA, the interpretation of the genetic sequence makes them unique and ultimately regulates their differentiation. In complex organisms such as the human, cell-type heterogeneity is extensive and is only just being unravelled using single-cell genomics. Understanding this diversity is crucial to appreciating tissue function in healthy and disease conditions. The placenta is an exceptional tissue: it is transitory, regulating fetal growth and has unique methylation (5mC & m6A) profiles. Bioinformatic deconvolution of transcriptome and methylome datasets, combined with single-cell multi-omic analysis, will help resolve the heterogeneity that exists in this tissue across gestation and shed light on the relationship between transcriptome state, cellular phenotype and identify biomarkers associated with complicated pregnancies.

We are looking for an enthusiastic and ambitious student to generate and analyse multiple NGS-datasets to better understand placenta function in health and disease. 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 Wilfried Hearty at the Earlham Institute. In addition to the bench and bioinformatic training that is provided through this unique collaborative project, the successful candidate will acquire excellent personal and professional development training offered through the DTP programme. 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:

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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.