We are studying sex chromosomes and their impact on health and disease.
Male and female mammals have genetic and biological differences. Females have two X chromosomes, while males have one X chromosome and one Y chromosome. These sex chromosomes are responsible for differences in growth, behaviour and health between the sexes. We are studying the development, epigenetics, evolution and cell biology of the sex chromosomes in a range of organisms, including human, mouse and opossum and models, e.g. stem cells.
One specific area that we are studying is the role of sex chromosomes in disease. Many diseases show a sex bias. For instance, heart disease is more common in men, whereas Alzheimer’s disease is more prevalent in women. We are working to understand how the sex chromosomes contribute to these differences. Within this research area we have a special interest in infertility. This condition is common, affecting approximately 1 in 4 couples, and is increasing in prevalence. Sex chromosomes have an important role in the development of the reproductive organs and other tissues. Sex chromosome abnormalities are the most common genetic cause of infertility. For more information, see here:
- Disorders of the Sex Chromosomes, WikiLectures, 2020
- Global prevalence of infertility, infecundity and childnessness, WHO, 2020
- Artificial sperm for mice offers infertile men hope, The Times, 2017
A second area of interest is in X chromosome inactivation. This is the process in which one of the two X chromosomes in females is silenced, in order to balance the dose of X-linked genes with males. We study how X-inactivation occurs, how it interfaces with early embryo development, and how it evolved. In the latter case, we make use of a unique animal model, the marsupial opossum, which we have a colony of at the Crick.
Our final area of interest is germ cell surveillance, or the ways that cells sense errors in their own development. Errors in meiosis, the stage in germ cells when chromosomes exchange genetic information, are the leading cause of abnormal numbers of chromosomes arising in embryo development. We are studying the mechanisms in germ cells that aim to prevent these errors occurring.
In summary, our research could lead to a better understanding of sex differences in disease, and new ways of managing diseases in men and women.