The epigenome determines which genes are active in which tissues at what time – something the body regulates by, for example, packaging or opening the structure of genes. Which genes are packaged or accessible differs per tissue type, but can also change due to external influences, such as diet and lifestyle. The epigenetic composition of the genome steers the folding of DNA in the cell nucleus and regulates which parts of the DNA are easily accessible and which remain more packaged. ‘The epigenome plays an important role in creating and maintaining cell identity. All contain the same genetic material, but during embryonic development each cell matures into a specific cell type - such as a skin cell or muscle cell for example. Every cell is programmed, as it were, by epigenetic information', explains Verschure.
Single cells and technological breakthroughs
Each cell type has its own epigenetic make-up, in which certain genes are active and others are not. It is known that altered, derailed epigenetic makeup can cause various diseases. As if a cell lost its identity. Verschure: 'My research focuses on the origin of this variability in individual cells, the moment one cell starts to distinguish itself epigenetically from another. At the molecular level, each gene is found to have unique timing. Technological breakthroughs such as innovative techniques to modify the genome epigenetically provide many new possibilities for investigating epigenetic dynamics in individual cells.'
The epigenetic composition of the genome is influenced by environmental factors. Examples include diet, radiation and lifestyle. ‘Think of the stories about identical twins who, despite their identical DNA, still differ from each other,’ says Verschure.
Verschure is looking for causal relationships between changes in epigenetic folding and the subsequent response of cells. She is especially interested in how it is possible that neighbouring cells start to differ from each other. Verschure: 'How is it possible that one cell changes just a little bit but as a result may completely derail and grow into a tumour cell? In addition to genetic changes, the epigenome plays an important role in variation between 'identical' cells of a cell type. This knowledge is important for the development of medical treatments. Perhaps we can intervene in the original changes at the epigenetic level.’
A plethora of applications
‘If you look at the average of a group of cells, an abnormal cell is not easily detected. Tumours show a high variety between cells. Due to this, treatments might only treat part of the cell population effectively.' Verschure coordinated the international EpiPredict consortium, which focused on the role of epigenetics in developing immunity to the treatment of hormone-sensitive breast cancer. Verschure: 'Breast cancer patients can be treated well, but after five to ten years, 30 to 40% of them become resistant to the treatment. We want to understand what epigenetic reprogramming occurs and, if possible, adjust the cells epigenetically.' Verschure is currently working on a follow-up project. ‘We aim to map the responsiveness of genes for making epigenetic changes – with the CRISPR/Cas platform (Nobel Prize 2020) – and to further develop it as a key technology. We focus not only on epigenetically adjusting dysregulated breast cancer and cells that regulate the immune system, but also on skin cells that have been altered by aging and UV radiation and from a biotechnological perspective on making plants with new properties to survive climate changes.'
Verschure studied Medical Biology at the UvA. She did her PhD research on cartilage degradation in rheumatoid arthritis in Nijmegen at Radboudumc. She then worked as a visiting researcher with fellowships in the United States. She received several prestigious grants (NWO-PULS, -Vidi, -Meervoud, KNAW), with which she started her own research group at the Swammerdam Institute for Life Sciences at the UvA. Verschure is involved in leading EU consortia, including as coordinator of the EU H2020 EpiPredict, working group leader in the COST Action International Nucleosome INC network and associate editor of Springer Nature journal Epigenetic Communications. With her chair Functional Dynamics of the Epigenome, Verschure will connect her fundamental research at the Faculty of Science (FNWI) with the clinical application at the Faculty of Medicine, Amsterdam UMC.