A therapeutic strategy for killing cancer cells by DNA repair inhibition

Research Opportunity
PhD students, Masters by Research, Honours students, Master of Biomedical Science
Department / Centre
Medicine and Radiology
Location
St Vincent's Institute of Medical Research
Primary Supervisor Email Number Webpage
A/Prof Andrew Deans adeans@svi.edu.au 92312505 Personal web page

Summary DNA damage drives cancer formation but also its treatment. BLM helicase is an enzyme that acts as a quality control factor during the repair of DNA damage. In this project you will drive the development of new small molecule-based strategies for targeting BLM for cancer treatment.

Project Details

DNA damage drives cancer formation. BLM helicase is an enzyme that acts as a quality control factor during the repair of DNA damage. As such, BLM is a critical tumour suppressor protein in normal cells. However, inactivation of BLM in cancer cells leads to a big increase in sensitivity to death by chemotherapy. In some cells, BLM inhibition can even kill in the absence of additional DNA damage, by a process known as “synthetic lethality”. In this project, you will investigate new strategies cells to inhibit the activity of BLM helicase in cells. The findings of your project will drive the development of new small molecule-based strategies for cancer treatment.

Our lab studies the mechanism of DNA repair by the BLM protein using cell-based and cutting-edge protein chemistry-based approaches, as well as structural biology.  Using these approaches, we have identified critical weakness points in BLM protein that could be targeted. You will work on development of peptide-based inhibitors of BLM, using biochemical reconstitution, and genetic inhibitors of BLM using normal and cancer-derived human cells. This project will also investigate the mechanism of DNA repair by the BLM protein using cell-based and protein chemistry-based approaches. A combination of approaches will be used such as cell culture with patient cell lines, studies on chemotherapy toxicity, protein interaction and expression studies and analysis of recombinant human BLM using state-of-the-art protein expression systems. This project is part of a larger NHMRC-funded study into the role of DNA repair in cancer initiation and chemotherapy.

Our team has a high Post Doc-to-student ratio so there will be plenty of research expertise and support for your project in the laboratory. By joining us you will gain exposure to basic and translational research that is at the forefront internationally. You will receive training in a molecular biology laboratory with a focus on biochemistry and cell biology, increase your understanding of cancer biology and treatment, and increase your employability particularly in the science sector.



Faculty Research Themes

Cancer

School Research Themes

Cancer in Medicine



Research Opportunities

PhD students, Masters by Research, Honours students, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department / Centre

Medicine and Radiology

Research Node

St Vincent's Institute of Medical Research

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