The Hackett group aims to understand the interplay between epigenetics, genome regulation and cell identity, with emphasis on transgenerational epigenetic inheritance.

Previous and current research

Epigenetic systems stabilise gene expression programmes and underpin cell fate decisions during development. The epigenome therefore acts as a stable ‘memory’ of differentiated cell identity. Nevertheless, epigenetic memory must be reset between generations in order to reacquire totipotency; the capacity of an early embryo to give rise to all cell types. The zygote and nascent germline therefore undergo a process of extensive epigenetic reprogramming, including DNA demethylation and chromatin remodelling, which restores cellular potential. At the same time, we have found that some epigenetic information escapes reprogramming and is therefore epigenetically inherited by offspring. If the balance between reprogramming and inheriting epigenetic states is adversely affected, this may have a significant impact on normal development, ageing and disease, potentially over several generations.

Future projects and goals

We are broadly interested in understanding the regulatory principles that govern epigenetic reprogramming, and the consequences of inheriting perturbed epigenetic states transgenerationally. We also aim to understand how epigenetic systems influence cell identity, using ES cells as a model. In particular we are interested in the link between epigenetics, retrotransposon regulation, and emergent cell states.

To address our interests we make use of a wide range of genetic and molecular tools, as well as mouse models. In particular we utilise state-of-the-art CRISPR/Cas9 genetic screening and epigenetic editing technologies, coupled with genomics, live imaging and developmental biology approaches.