Every cell in the body carries two copies of most genes—one from each parent—but for a small set of genes, only one copy is active. This research asks how the cell decides which copy to silence, and what happens when that decision goes wrong. The mechanism is epigenetic: chemical tags on the DNA mark one parental copy as “off” and the other as “on.” These marks must be set correctly during early development, but the process can be disrupted. The team will compare how the two chromosomes are physically packaged at imprinted regions, study a key imprinted gene active in the brain that is linked to human disease, and investigate a newly discovered ability of the early embryo to repair lost DNA methylation. They will test whether this repair fails in offspring of obese or older mothers, potentially altering the offspring’s lifelong health. This is fundamental science. It will not produce a treatment or diagnostic tomorrow. But understanding how epigenetic marks are established and maintained—and why they sometimes break—is essential for explaining why certain developmental disorders, metabolic conditions, and neurological diseases arise. Similar work on imprinting has already revealed mechanisms that underpin rare genetic syndromes and informed how environmental factors in pregnancy shape long-term health.
View original technical description
We are interested in understanding mechanisms of imprinted expression. What makes an imprinted gene be expressed from one of the chromosomes in a pair rather than both of them? The process causing only the paternally inherited or the maternally inherited copy to be expressed, is an 'epigenetic' one. Epigenetics means 'on top of genetics' and the epigenetic state at an imprinted gene is manifested as chemical modifications that sit on the DNA at only one parental chromosome and not the other causing the gene located there to be expressed on one of the chromosomes and kept off on the other. Our goal is to generate new knowledge about what the two parental chromosomes look like at an imprinted domain and how that influences one parental copy being on and the other being off. In our first aim we will compare the chromosome inherited from dad, with the chromosome inherited from mum, at an imprinted domain. This will allow us to identify if the two parentally inherited chromosomes are packaged differently from each other and in turn, whether this is a cause or a consequence of the expression or repression of the genes in the domain being investigated. In our second aim, we study a very important imprinted gene predominantly in the brain, to try and understand more about human diseases that are associated with abnormalities in this gene. Finally, we have recently discovered that the preimplantation embryo is able to 'repair' lost DNA methylation. This resilience to methylation loss has implications for offspring health and well being. In our third aim, we will characterise the sequences where methylation can be restored and the machinery that does the restoration. In particular, using the mouse as a model, we will investigate whether this process is compromised in obese mothers or aged mothers leading to abnormal methylomes in their offspring with implications for their life long health.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know