The Link Between Aberrations in the P53 Pathway and Outcome from DNA-Damaging Therapies in Breast Cancer
Closing Date: 30 June 2019
This project will involve analysis of breast cancer tissues by IHC and next-generation sequencing; as well as functional investigation in pre-clinical cell line models, to determine how aberrations in the p53 pathway affect DNA-damaging therapy outcome in breast cancer.
Breast cancer is the second-leading cause of cancer-related deaths in Australian women, accounting for over 3000 deaths in 2017. DNA-damaging therapies are common in breast cancer treatment, yet there is no standardised test that predicts their efficacy. The vast majority of breast cancer deaths are due to treatment resistance. To reduce the number of lives lost from breast cancer, a predictive test that indicates whether the pathway being targeted is functional is required. Breast cancer is a result of abnormal cell growth. The tumour suppressor gene p53 is essential for maintaining normal cell growth and repairing damaged cells. It is the single most commonly mutated gene in cancer, but despite this, almost all cytotoxic therapies used in breast cancer activate this pathway. Somatic mutation of p53 is associated with breast cancer development and progression, but its power as a predictive biomarker of treatment response is yet to be realised. p53 is expressed as a number of smaller isoforms, which are critical for its function. The Breast Cancer Group at the Hunter Medical Research Institute have been studying p53 isoforms for a number of years and have shown that they are a better predictor of outcome than p53 mutation status in breast cancer. The overall aim of this project is to develop a novel predictive assay which takes into account aberrations in p53 signalling and its isoforms. This will be done using immunohistochemistry and next-generation sequencing in breast cancer cohorts. The effect of these aberrations on the response to selected DNA-damaging therapies will also be tested in pre-clinical cell line models. The results of this study will provide novel information on aberrations in the p53 pathway that contribute to treatment outcome in breast cancer. The project will be carried out at the Hunter Medical Research Institute (located on the John Hunter Hospital Campus). The student will have the opportunity to gain experience in 3D cell culture assays, microscopy techniques, cutting edge genomic analysis as well as a number of assays to investigate cell viability. The student will join a highly supportive team and will have access to cutting-edge laboratory equipment, excellent mentoring and possible overseas collaborative opportunities.
PhD Scholarship details
Funding: Funded by the Cancer Institute NSW. $27,596 per annum (2019 rate) indexed annually. For a PhD candidate, the living allowance scholarship is for 3.5 years and the tuition fee scholarship is for four years.
Supervisor: Dr. Kelly Kiejda
Available to: Domestic students
The applicant will have an interest in breast cancer. Applicants should have a strong work ethic, as well as strong communication and teamwork skills. Strong proficiency in English is essential. Previous research experience, particularly in molecular biology is desirable. The successful applicant must be able to commence their PhD by 31 March 2020. Please also refer to the admission eligibility criteria.
Interested applicants should send an email expressing their interest along with scanned copies of their academic transcripts, CV, a brief statement of their research interests and a proposal that specifically links them to the research project.
Please send the email expressing interest to Kelly.Kiejda@newcastle.edu.au by 5pm on 30 June 2019.
Applications Close 30 June 2019
|Contact||Dr. Kelly Kiejda|
|Phone||+61 2 4042 0309|
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