2020 Joint Winners
Two Reik lab members, Melanie Eckersley-Maslin, a BBSRC Discovery Fellow, and Stephen Clark, a senior researcher, were jointly awarded the 2020 Sir Michael Berridge Prize. This year’s Prize is especially poignant due to the loss of Sir Michael in February this year.
Melanie’s award recognised her two publications on the roles of Dppa2 and 4 in the epigenetic regulation of transcription during early development and in maintenance of pluripotency. Melanie’s research investigates the process of epigenetic priming where genes that are not yet active but needed in later development are ‘protected’ from permanent silencing during the genome-wide changes that occur during early development.
Melanie’s work identified developmental pluripotency associated 2 (Dppa2) and 4 (Dppa4) as epigenetic priming factors in early embryos. As a whole, Melanie’s research has uncovered how epigenetic priming factors are important gatekeepers of early embryonic cell fate transitions and raises future questions on how these mechanisms may go awry in disease.
Stephen’s award recognised his leading contributions to collaborative landmark papers establishing methods enabling multi-omic profiling of single cells and their application to understanding gastrulation, the process of mammalian germ layer specification. Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes. Global epigenetic reprogramming accompanies these changes but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear.
In collaboration with researchers at several Cambridge research institutes, Stephen contributed to the development of a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The resolution of this approach generates new understanding about the epigenetic priming events that determine the cellular types that emerge later in development.
Eckersley-Maslin, M. et al. Epigenetic priming by Dppa2/4 in pluripotency facilitates multi-lineage commitment. Nature Structural & Molecular Biology. DOI: 10.1038/s41594-020-0443-3.
News item, 22 June 2020: Early preparation allows genes to ‘come online’ later
Eckersley-Maslin et al. Dppa2 and Dppa4 directly regulate the Dux driven zygotic transcriptional programme. Genes and Development DOI: 10.1101/gad.321174.118
News item, 28 January 2019: Kick-starting the genome in early development
Argelaguet, Clark, Mohammed, Stapel et al. Multi-omics profiling of mouse gastrulation at single-cell resolution. Nature. DOI: 10.1038/s41586-019-1825-8
News item, 11 December 2019: Single-cell analysis of the earliest cell fate decisions in development
Stephen J. Clark, S.J. et al. scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells. Nature Communications (2018) DOI: 10.1038/s41467-018-03149-4
News item, 22 February 2018: New technique offers insights into early life