Study level

  • Honours

Faculty/School

Faculty of Health

School of Biomedical Sciences

Topic status

We're looking for students to study this topic.

Research centre

Supervisors

Dr Emma Bolderson
Position
Senior Research Fellow
Division / Faculty
Faculty of Health
Dr Didier Boucher
Position
Visiting Fellow
Division / Faculty
Faculty of Health
Dr Joshua Burgess
Position
Visiting Fellow
Division / Faculty
Faculty of Health

Overview

Our cellular DNA is constantly under threat from both exogenous and endogenous factors. DNA repair pathways function to maintain genomic stability, preventing deleterious mutations that may ultimately lead to cancer initiation. When a tumour forms, it becomes genetically unstable, allowing environmental adaptation. This genetic instability can also result in gene mutations and protein expression alterations that can be targeted to induce cancer-specific cell death (phenomenon also known as synthetic lethality). For example, it has been shown that cells deficient in DNA double-strand breaks repair by homologous recombination are highly sensitive to the inhibition of the DNA repair protein PARP1.

The aim of my research is to improve the efficiency of PARP inhibition treatment.

Data generated in the lab has identified a protein as a predictive biomarker for PARP inhibitor sensitivity in ovarian cancer. Our in-vitro data indicates that depletion of this protein in ovarian cancer cell lines markedly increases the sensitivity to PARP inhibitors

This project will determine if modulation of our biomarker levels in ovarian cancer cells grafted in mice impacts tumours response to PARP1 inhibitors treatment, providing in-vivo validation of our therapeutic biomarker.

To induce the modulation of the biomarker level, you will silence and overexpress protein expression with a tetracycline-inducible lentiviral system. You will also tag the cells with a luciferase reporter gene to image the grafted tumours in live animals (IVIS bioluminescence imaging system, weekly analysis).

You will be trained in the animal facility to handle mice, measure tumour volumes and deliver treatments.

Approaches, skills and techniques

  • Cancer cell line culture.
  • Generation of genetically modified cell lines.
  • Mouse handling.
  • Xenograft models.
  • Tissue processing.
  • Data analysis.

Outcomes

This proposal presents a unique approach to redefine ovarian cancer patients who will benefit from the PARP inhibitor therapy. At the end of this proposal you will have defined the prognostic significance of a novel biomarker for ovarian cancer.

Keywords

Contact

Contact the supervisor for more information.