Identifying new drivers of lung cancer

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Summary

This project will identify and investigate novel genes mutated in a Kras-induced mouse model of lung adenocarcinoma

Supervisor(s)

Dr Viive Howell, Dr Emily Colvin

Research Location

North Shore - Kolling Institute of Medical Research

Program Type

Masters/PHD

Synopsis

Lung cancer is the leading cause of cancer-related death globally with very few effective therapies. Advances in genetic characterisation of tumours have led to the identification of a number of abnormalities in lung cancer that can be treated with targeted therapies. However, for the vast majority of patients there are no effective treatments. A significant proportion of patients have mutations in the cancer-causing gene KRAS, which is difficult to target therapeutically. This project will use insertional mutagenesis to generate a novel preclinical model for identification of genetic mutations that cooperate with KRAS to promote lung cancer progression. These mutations will provide other genes that can be targeted to treat KRAS-mutant lung cancer patients more effectively.

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 cut-and-paste activity of the transposons (called T2/ONC3) in the mouse genome is catalysed by SB transposase. Integration of a transposon within a gene results in insertional mutagenesis of that gene. 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 including pancreatic cancer. This technology will enable the identification of new therapeutic targets and lead to the development of better preclinical models of lung 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.

Additional Information

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.

For more information please see the Bill Walsh Translational Cancer Research Laboratory website: http://www.bwcancerresearchlab.org.au/

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Keywords

lung cancer, Cancer, Genetics, mouse model, Oncogene, mutagenesis, targeted therapy

Opportunity ID

The opportunity ID for this research opportunity is: 1781

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