Cancer drug discovery by inhibition of a DNA repair pathway with Crispr/Cas9 gene editing and biochemistry

Summary In this project, you would learn about DNA repair, genetic diseases like familial breast cancer, and a variety of laboratory-based techniques (CRISPR/Cas9 gene-editing in breast cancer cell lines, AlphaScreen drug discovery assays, recombinant DNA technology, drug discovery, cell-based chemotherapy response assays, pharmacokinetics, protein purification and in vitro enzyme assays).

Project Details

Want to cure cancer? We do too. Join our dynamic young team of experts, in the identification and characterisation of new potential cancer therapeutics. In this project, you would learn about DNA repair, genetic diseases like familial breast cancer, and a variety of laboratory-based techniques (CRISPR/Cas9 gene-editing in breast cancer cell lines, AlphaScreen drug discovery assays, recombinant DNA technology, drug discovery, cell-based chemotherapy response assays, pharmacokinetics, protein purification and in vitro enzyme assays).

A new mechanism being used to kill cancers is synthetic lethality – a combination of deficiencies in the expression of two or more genes leads to cell death, whereas a deficiency in only one of these genes does not (see Kais et al below). Our team is working towards identifying new targeted breast and ovarian cancer treatments, which exploits synthetic lethality. The team has made major breakthroughs in reconstituting the necessary DNA repair reactions in vitro, allowing new approaches to design DNA repair-inhibiting drugs. We already have many candidate drugs and gene-editing projects waiting for a motivated candidate.

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.

$5,000 PhD top ups and Honours scholarships are available to a limited number of outstanding candidates. Scholarships are awarded on a competitive basis and at the discretion of St Vincent's Institute of Medical Research.

Background reading
1.Van Twest et al 2017. Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway. Molecular Cell
2.Kais et al 2016. FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair. Cell Reports