This project will use insertional mutagenesis in mice to identify and investigate potential genetic drivers of ovarian carcinogenesis.
Ovarian cancer is the 6th most common cause of cancer related deaths in Australian women, with high-grade serous epithelial ovarian carcinoma being the most common and aggressive subtype. Improving early diagnosis for ovarian cancer is recognised as a major public health issue; however, despite concerted research this has not been realised and the majority of women have distant metastases at diagnosis. Defining the sequence of events that give rise to this malignancy is critical if improvements in early diagnosis and treatment are to be made. However, as the disease is invariably diagnosed at a late stage, there is a scarcity of tissue and no human cell lines in which to study early changes. This is compounded by the paucity of robust genetically engineered models of this malignancy for monitoring the natural history of the malignancy and preclinical testing of novel therapeutics. Sleeping Beauty (SB) insertional mutagenesis is a recent genetic technology developed to induce cancer in mice by generating mutations through the insertion of DNA transposons. The transposon tags the mutated gene, enabling identification of targeted genes and the primary genetic changes required for tumour development. SB mutagenesis has already been used successfully to identify novel driver mutations in several cancer types. Genes identified from tumours induced by surgical activation of this system in the ovary will be investigated as potential oncogenic driver genes. Additional models will be also assessed for increased penetrance and suitability as preclinical models of ovarian cancer.
The candidate will gain experience in a variety of molecular, cellular and transgenic mouse techniques including mammalian cell culture, adenoviral and lentiviral transduction, immunohistochemistry, PCR and quantitative RT-PCR. They will work in the Bill Walsh Translational Cancer Research Laboratory located in the state-of-the-art Kolling Building based at Royal North Shore Hospital.
Honours projects based within or related to the above project are also available
Interested students are asked to apply for all available funding (eg. APA, UPA, NHMRC Dora Lush, CINSW Research Scholar Awards etc.). The potential supervisors will help with this process.
Bill Walsh Translational Cancer Research Laboratory The Bill Walsh Lab is the research arm of the Medical Oncology department at Royal North Shore Hospital and has a major interest in research driven by clinical issues including personalised medicine, cancer vaccine development, model development, drug discovery and predictive biomarkers. The lab currently comprises 15 people and includes post-doctoral and post-graduate research scientists, medical oncologists, surgeons and PhD students.
In addition to ovarian cancer, the lab is involved in clinical trials and on-going laboratory based projects in a number of other cancers including lung, colorectal, mesothelioma, breast, melanoma and leukemia. The Kolling Institute provides a dynamic academic environment for students with seminar programs, journals clubs, and an active student group PReSS
The opportunity ID for this research opportunity is 1197