Comparative genomics is important for our understanding of the evolution of the molecular basis of mammalian biology but can also identify disease causing changes in genes and whole pathways. Our work on the iconic Australian egg-laying mammals has provided novel insights into the fascinating biology of the platypus and echidna and revolutionised our understanding of the origin of our own sex chromosomes. This has also let to the Identification and characterization of novel genes involved in monotreme reproductive biology which are also candidate genes for reproduction in other mammals.
Comparative analysis can also further our understanding of human disease as evidenced by our work on the piRNA pathway in the mammalian ovary and ovarian cancer. The piRNA pathway is important for various aspects of germ cell biology and genome integrity. Based on our previous work that showed expression of piRNA pathway genes in mammalian ovary we investigated the expression of these genes in ovarian cancer and found overexpression associated with increased malignancy.
We investigated if this change in piRNA pathway activity is reflected in signature changes in small RNA profiles. Small RNA sequencing of the early and late tumours revealed less than 1% of known piRNAs present. This is consistent with other cancer small RNA datasets where the proportion of known piRNAs was also low but extensive mapping to tRNA fragments and other RNAs was observed. This raises the possibility of other, yet unknown roles of piRNA pathway genes potentially in the regulation of translation. In order to better understand the direct roles of this pathway in ovarian cancer progression we currently overexpress those pathway genes in ovarian cancer cell lines and measure effects on invasiveness, proliferation, stemness and epithelial to mesenchymal transition.