Grant: Operating Grant - Priority Announcement: Ovarian Cancer (bridge funding)

The human genome encodes approximately 22000 protein-coding genes. Depending on the cell type, the actual protein content varies as controlled not only by gene expression regulation but also through the process of alternative splicing, which allows the production of different proteins from a single gene. Although alternative splicing has been extensively investigated, the regulation of many tissue-specific alternative splicing events is poorly understood. Many forms of cancer including ovarian cancer are characterized by alterations in splicing programs highlighting the importance of a comprehensive understanding of this regulation. Small non-coding RNAs represent an abundant and diverse group of molecules, many of which have been recently described as involved in the regulation of essential cellular processes. Preliminary evidence suggests a role for specific types of small RNAs in the regulation of alternative splicing. Some such small RNAs have recently been discovered to be much more abundant in cancer cells including ovarian cancer than in healthy cells. In light of these recent findings, we propose to characterise specific families of small RNAs and to study their regulatory role in alternative splicing, in normal and ovarian cancer cells, using computational and experimental methods. We will also study the consequences of their deregulation in ovarian cancer, which will be instrumental in devising urgently needed methods for the detection and treatment of this disease.