Grant: Project Grant

The contractile activity of the smooth muscle component of the uterus, the myometrium, generates the force needed to expel the fetus at birth. To initiate contractions, individual smooth muscle cells within the myometrium turn on a group of genes in response to hormonal, mechanical and inflammatory signals. In many patient cases this cell-coordinated contractile response occurs prior to term; women can consequently enter labour too early, which results in the delivery of underdeveloped infants at high risk of death or complications later in life. There is currently no effective treatment for preterm labour. Recent research has identified activated genes in the myometrium at term and preterm labour; however, the mechanisms that stimulate expression of these genes remain unclear. To understand the basis of preterm labour and develop new preterm labour therapies, we need to find the components involved in activating genes in both term labour and preterm labour. Inside cell nuclei the DNA that makes up our genome is highly organised into three dimensional structures so that regions of the genome that turn genes on or off can contact the genes they regulate. This genome organisation is specific to each cell type which ensures genes are expressed in the correct context. Currently, genome organisation in the myometrium as well as the parts of the genome that regulate gene expression changes during pregnancy and labour are unknown. Out team will identify the three dimensional genome structures specific to myometrial cells and the labour process. In addition, we will identify the proteins that bind to the genome to regulate gene expression during preterm or term labour. Uncovering the suite of genomic regions and regulatory proteins that underlie the labour process will provide new targets for the development of therapeutic treatments for preterm labour, preventing complications that occur when babies are born preterm.