Our lab is interested in epigenetic gene regulation in mammalian development and in ageing. Global epigenetic reprogramming occurs at fertilisation and fundamentally remodels the epigenomes of sperm and egg. We are working to understand the mechanisms of reprogramming and also how it may be linked with zygotic genome activation, the sudden transcriptional springing to life of the genome in the early embryo.
Soon after implantation of the embryo in the maternal uterus there is a major programme of cell fate decisions which establishes the three primary germ layers, the ectoderm (which gives rise to brain and skin), the mesoderm (giving rise to muscle and heart), and the endoderm (which gives rise to the gut amongst other tissues).
These three lineages are the foundations of all organs in the adult body and we are interested in the transcriptional and epigenetic events that underlie their emergence from the undifferentiated epiblast. Finally, we are studying how the epigenome degrades during ageing potentially in a programmed fashion, and whether there are approaches by which this degradation can be slowed down or reversed.
Perturbation of DNA methyltransferases (DNMTs) and of the active DNA demethylation pathway via ten-eleven translocation (TET) methylcytosine dioxygenases results in severe developmental defects and embryonic lethality. Dynamic control of DNA methylation is therefore vital for embryogenesis, yet the underlying mechanisms remain poorly understood.
Biological systems have the capacity to not only build and robustly maintain complex structures but also to rapidly break up and rebuild such structures. Here, using primitive societies of Polistes wasps, we show that both robust specialization and rapid plasticity are emergent properties of multi-scale dynamics. We combine theory with experiments that, after perturbing the social structure by removing the queen, correlate time-resolved multi-omics with video recordings. We show that the queen-worker dimorphism relies on the balance between the development of a molecular queen phenotype in all insects and colony-scale inhibition of this phenotype via asymmetric interactions. This allows Polistes to be stable against intrinsic perturbations of molecular states while reacting plastically to extrinsic cues affecting the whole society. Long-term stability of the social structure is reinforced by dynamic DNA methylation. Our study provides a general principle of how both specialization and plasticity can be achieved in biological systems. A record of this paper's transparent peer review process is included in the supplemental information.
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