The loopy placenta: defining higher-order chromatin contacts in this essential developmental tissue

MONK_U22DTP1

Our previous work has revealed that the human placenta has a unique epigenome compared with somatic tissues. This developmentally important organ has relatively low levels of DNA methylation which is dynamic during gestations. In order to understand the consequence of such global hypomethylation on additional epigenetic layers, it is crucial to dissect chromatin accessibility profiles in different cells and compare them with histone modifications and DNA methylation. This project will involve generating global expression and chromatin accessibility profiles in placenta samples at both bulk and at single-cell resolution using RNA-seq and ATAC-seq technologies. Bioinformatic deconvolution of transcriptome and accessibility datasets, combined with single-cell multi-omic analysis, will help resolve the heterogeneity that exists in this tissue across gestation and is crucial to appreciating tissue function in health and disease.

We are looking for an enthusiastic and ambitious student who is keen to unite both laboratory and computations skills to develop and apply NGS protocols to understand how chromatin accessibility influences gene regulation in the human placenta. The project is a joint Norwich Research Park venture between the groups of Dr David Monk and Professor Grant Wheeler at the University of East Anglia and Dr 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. All candidates are strongly advised to contact the PI to discuss the projects prior to formal application.

References 

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

López-Abad M, Iglesias-Platas I, Monk D. Epigenetic Characterization of CDKN1C in Placenta Samples from Nonsyndromic Intrauterine Growth Restriction. Front. Genet. 2016, 7:62.