Epigenetics

The activity of our genes is determined by more than their DNA sequence alone. Epigenetic marks include reversible chemical modifications to our DNA (DNA methylation) and how the DNA is wound around histone proteins as it is packaged in the cell nucleus. Epigenetic modifications alter the activity of genes, determining whether they are accessible and 'on', or inaccessible and 'off'.

Epigenetic marks play important roles in defining different cell types in the body, including as cells differentiate from stem cells during development, and can be influenced by environmental and nutritional factors. It is known that epigenetic marks are affected by ageing and these changes can be used to read the 'epigenetic clock' to provide accurate read-outs of biological age.

The sum of epigenetic marks in a tissue is known as the epigenome.

Our research explores how epigenetic control influences trans-generational inheritance, including how the epigenome reflects nutritional and environmental experiences, and the role of epigenetic regulation throughout development. We are particularly interested in the epigenomes of the stem cells that contribute to, and are present in, the early embryo and in understanding how cell identity is established and can also be manipulated (through the process of cellular reprogramming).

Our research will provide approaches by which epigenetics can be manipulated in cells and organisms, potentially leading to enhanced stem cells and applications in regenerative medicine, improved assisted reproduction technology, and healthy ageing.

Using state-of-the-art technology, most of which we have developed ourselves, we are performing analyses to study the epigenome and gene expression patterns in mammalian development and also through the lifecourse of model systems (yeast and nematode worms). This information allows us to unravel how epigenetic marks influence development and confer cell identity and how the epigenome changes as a result of ageing and environmental stress.

We are defining the signalling pathways in stem cells that induce reprogramming of the epigenome on a large scale. Additionally, we are studying the enzymes that regulate the epigenome together with factors such as RNA that can help to target specific epigenetic marks. Understanding the epigenetic mechanisms at play and how these are altered during disease is required before they can be targeted for therapeutic effect.