An integrative approach to tissue-specific effects of microRNA regulatory networks Supervisor: Margarida Gama-Carvalho (BioISI) | Co-supervisor: Nham Tran, UTS Objectives: Generate a comprehensive map of tissue-specific miRNA-dependent regulatory networks in normal and cancer cells, improving current target-prediction methods

Background: The Gama-Carvalho lab has recently uncovered an unexpected role in T lymphocyte activation for a member of the miR-34/449 family, well known for its role in neuronal differentiation, stem cell maintenance and cancer. Interestingly, most of the known targets for this miR do not exhibit tissue specific expression. In parallel, the Tran lab has shown that the expression of a highly specific ‘myomiR’, miR-499, is dysregulated in oropharyngeal cancers, eventually contributing to tumorigenesis. These observations raise the question of how miRs influence distinct phenotypic outcomes across different tissue types. Our ongoing bioinformatics work has revealed the prevalence of miR sequence variants that can potentially impact tissue-specific regulation, compounded by 3’UTR sequence variation. Furthermore, results from the Tran lab show that cooperative interactions between highly expressed and low abundance miRs influence regulatory outcomes. In spite of the increasing data availability, these aspects are not currently incorporated into target prediction algorithms.