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Investigating the biology of novel homeobox gene fusions in paediatric cancer

Centre for Childhood Cancer Research

, Applications accepted all year round Competition Funded PhD Project (Students Worldwide)

About the Project

Cancer in children, as in adults, is a disease caused by the accumulation of somatic mutations in previously normal cells. In many paediatric malignancies, a frequent event is the fusion of 2 genes to form a novel active oncogene which then drive the phenotypic traits (hallmarks) of cancer cells including unregulated proliferation and a resistance to cell death (apoptosis). We have identified several novel fusions which, as a common feature, drive the expression of homeobox genes, normally expressed during early development and which are thought to regulate gene expression programs controlling differentiation.

In this project, the student will use the tools of molecular and cellular biology to determine the mechanisms by which these novel homeobox oncogenes function to drive proliferation, repress cell death, regulate differentiation and activate oncogenic signalling pathways. The broad aims of the projects will include;
1. Determining how these fusions regulate differentiation programs using in vitro and in vivo model systems.
2. Identifying where in the genome the fusions bind, the molecular complexes in which they function, and the changes in gene expression they induce.
3.Use high-throughput drug screens to identify potential targeted therapies.

This project will engage the student in cancer biology and the generation of new models to study these fusion genes. Techniques such as CRISPR/Cas9 to modify genes and generate generate endogenous fusions, RNA sequencing, ChIP sequencing, protein analysis including phosphoproteomics will be employed in this project and the student will develop valuable skills in these methodologies.

The overall aim of this project is to determine the mechanisms by which homeobox fusion oncogenes drive cancer and use this molecular insight to identify ways in which these novel fusions can be therapeutically targeted.

Funding Notes

To help us determine your suitability for postgraduate studies with us could you please send through a copy of your full academic transcript.
All students at the Institute must fulfil the requirements for enrolment at UNSW to undertake their PhD with us as well as obtain a scholarship that will cover both your living expenses and tuition fees. Scholarship and entry requirements will be provided on request.

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