Molecular drivers of metastasis

Mitochondrial genes as potential therapeutic targets for metastatic prostate cancer

Degree type

PhD

Closing date

10 October 2022

Campus

Hobart

Citizenship requirement

Domestic/International

About the research project

The vast majority of deaths associated with solid tumours are due to metastatic disease. Aggressive prostate cancers (PrCa) are particularly problematic as these tumours have a high propensity to metastasise to bone. Five-year survival for men with bone metastatic PrCa lesions is ~6%, and current therapies available are both limited and largely ineffective. Lethality-based genome-wide (CRISPR/Cas9) screens are an innovative technique used to uncover the genes that underpin complex disease, the outcomes of which are seeding important advances particularly for cancer treatment. We have performed a successful lethality-based genome-wide screen in an aggressive prostate cancer cell line (isolated from a patient with bone metastases) and identified several mitochondrial-associated genes as the top ranked genes driving survival and metastatic behaviour. Mitochondria, as the cell's powerhouse, are known to sustain tumour cell proliferation and survival, and this project seeks to uncover how these genes are critical to the metastatic cell state in PrCa, and further how this knowledge can be harnessed to develop much needed therapeutic interventions for metastatic disease. Our close clinical collaboration with both public and private prostate cancer treatment service providers has enabled us to develop a rare clinically annotated biospecimen resource comprising matched primary and metastatic tumour specimen.

In this project, we will explore the functionality of the identified genes and their role in influencing cell proliferation, migration, and mitochondrial functional assays in vitro, in addition to their influence on metastasis in a xenograft zebrafish model. Further, we will utilise our existing extensive clinically annotated prostate tumour pathology resources to explore association of these genes with clinicopathological features of PrCa. A second focus of our work will be to explore the influence of these genes on sensitivity to current radiotherapeutic and chemotherapeutic interventions and their putative value as prognostic indicators of therapeutic response, and or as therapeutic targets for drug intervention.

Primary Supervisor

Meet Dr Kelsie Raspin

Funding

Applicants will be considered for a Research Training Program (RTP) scholarship or Tasmania Graduate Research Scholarship (TGRS) which, if successful, provides:

  • a living allowance stipend of $28,854 per annum (2022 rate, indexed annually) for 3.5 years
  • a relocation allowance of up to $2,000
  • a tuition fees offset covering the cost of tuition fees for up to four years (domestic applicants only)

If successful, international applicants will receive a University of Tasmania Fees Offset for up to four years.

As part of the application process you may indicate if you do not wish to be considered for scholarship funding.

Eligibility

Applicants should review the Higher Degree by Research minimum entry requirements.

Additional eligibility criteria specific to this project/scholarship:

  • Applications are open to onshore applicants only
  • Applicants must be able to undertake the project on-campus

Selection Criteria

The project is competitively assessed and awarded.  Selection is based on academic merit and suitability to the project as determined by the College.

Additional desirable selection criteria specific to this project:

  • Skills in molecular biology and analysis of genetic data would be favourable

Application process

There is a three-step application process:

  1. Select your project, and check you meet the eligibility and selection criteria;
  2. Contact the Primary Supervisor, Dr Kelsie Raspin to discuss your suitability and the project's requirements; and
  3. Submit an application by the closing date listed above.
    • Copy and paste the title of the project from this advertisement into your application. If you don’t correctly do this your application may be rejected.
    • As part of your application, you will be required to submit a covering letter, a CV including 2 x referees and your project research proposal.

Following the application closing date applications will be assessed within the College. Applicants should expect to receive notification of the outcome by email by the advertised outcome date.

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