Radiation therapy is administered to approximately half of cancer patients and responsible for 40% of cancer cures. Development of new technologies enables administration of high dose radiation within precise spatial targeting, termed ablative radiotherapy (ART), to kill tumour cells while sparing the surrounding healthy tissue. While it is clear ART kills cancer cells, the mechanism of cell death, and the genetic pathways that promote radiation therapy sensitivity and resistance are unknown.
Our research identified that ART induces distinct waves of cancer cell death. Surprisingly, we find that how and when cells die relative to radiation treatment is a function of DNA repair pathway engagement. In this project we are examining how DNA damage response and repair pathways, cell cycle regulation, inflammatory signalling, and environmental factors impact the molecular and cellular outcomes following ART. We are specifically interested in understanding how cellular process can be tuned to improve ART outcomes and identifying the specific molecular pathways that regulate cell following radiotherapy. We will tailor opportunities in this project to applicants’ interests and strengths on an individual basis.
Our laboratory utilizes cutting edge cell and molecular biology techniques to study genome integrity in human cells, with a primary focus on radiation oncology, DNA replication, and telomere biology. Much of our research uses advanced imaging platforms including spinning disk confocal and wide field live cell imaging systems, super resolution microscopy, and automated image capture and analysis. The lab also employs viral vector shRNA and CRISPR systems for modification of gene expression. Additionally, we have completed whole genome CRISPR/Cas9 screen and interactomics using proximity ligation and mass spectrometry. These research activities are supported by multiple Australian Cancer Research Foundation supported facilities at our institute. We are also always on the lookout for talented young individuals who can bring new experimental techniques to our lab.
Methodologies used in this project may include: viral vector based gene expression modification (shRNA, CRISPR); CRISPR screen; Live cell imaging (widefield and confocal); Fixed imaging (confocal and widefield); Automated image capture and analysis; Super-resolution microscopy; Cell based assays to measure genome instability and viability; Flow cytometry; Standard molecular biology and biochemistry (western blot, Chromatin Immunoprecipitation, etc); Mass-spectrometry (for selected students with interest and previous experience); DNA fiber analysis, ChIP and ChIP-seq (for selected students with interest and previous experience)
PhD entry: Hons I classification, lab-based research experience is preferable. Our lab has a strict policy that all Ph.D. candidates must attract external funding (such as an APA, IPA, IPRS, etc).
Additional Supervisor: Harriet Gee
The opportunity ID for this research opportunity is 3042