Cells have developed a vast array of repair and signalling proteins in order to prevent the loss of valuable genetic information that results from DNA damage. Our work centres on elucidating the roles of two newly identified single-stranded DNA binding proteins designated as SSB1 and SSB2 that plays a crucial role in the repair of DNA damage. We have generated conditional knockout mouse models for these genes and we have published phenotypic characterization of SSB1 in a recent paper in Plos Genet. 2013;9(2):e1003298. The SSB1 knockout mice die at birth from respiratory failure due to severe rib cage malformation and impaired alveolar development, coupled with additional skeletal defects, indicating that Ssb1 is necessary for proper development of the embryonic skeleton.
Furthermore, conditional deletion of Ssb1 in adult mice led to increased cancer susceptibility with broad tumour spectrum, impaired male fertility with testicular degeneration, and increased radiosensitivity and IR–induced chromosome breaks, indicating Ssb1 is essential for spermatogenesis, and genome stability in vivo. Interestingly, we observed profound upregulation of Ssb2 protein levels in bone marrow and spleen from conditional Ssb1-/- mice, indicating a potential functional compensation between these two proteins. To further investigate this aspect, we generated double inducible knockout mouse model of Ssb1 and Ssb2 (DKO) and we will use Ssb1-/-, Ssb2-/- and DKO mouse models to comprehensively characterize their roles in embryogenesis, spermatogenesis, and genome stability in vivo. The studies using knockout mouse models will help us understand unique and overlapping roles of these proteins in the various organs of a living organism.
Expected outcomes and deliverables
Scholars will gain skills in cell biology, molecular biology and/or animal techniques including tissue culture, immunofluorescence, western blotting, FACS, animal handling and dissections and Xenograft Tumour Models.
- Suitable for students with a background in biology who are looking to undertake Honours or a PhD in the future.