PhD opportunities & Honours Projects

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PhD Project 1: Targeting 'metastasis initiating cells' in prostate cancer

Supervisor: Prof Peter Croucher

Bone metastases are a devastating clinical consequence for patients with prostate cancer. The mechanisms leading to their development are poorly defined, and approaches to prevention and treatment limited. We have developed new high-resolution imaging technology that allows us to visualize the tumour initiating cells, at a single cell resolution, in the skeleton. Projects in this area will use the latest imaging technology and next generation genetic and bioinformatic tools to establish a genetic and molecular fingerprint of these tumour-initiating cells and utilise this knowledge to develop new therapeutic approaches to preventing the development of bone metastasis.

 

PhD Project 2: Anti-tumour effects of bisphosphonates

Supervisor: Prof Mike Rogers & Dr Marcia Munoz

Bisphosphonates are a class of drugs that inhibit protein prenylation and are used to prevent bone destruction in patients with bone metastases. Bisphosphonate therapy has also been shown to prolong the survival of some patients with cancer and has anti-tumour activity in various animal models, but the exact mechanisms remain unknown. This project will seek to identify exactly how these drugs prevent tumour growth, particularly focusing on their effects on myeloid cells of the immune system, such as macrophages (Junankar et al, Cancer Discovery 2015). In vivo and ex vivo 2-photon microscopy and flow cytometry will be used to determine the tissue distribution and cellular uptake of fluorescently-tagged bisphosphonates in mouse models of cancer. We will also use a wide variety of molecular, biochemical and imaging techniques to examine how bisphosphonate treatment affects the function of myeloid cells in mice and in cancer patients, and whether such effects are mediated via inhibition of protein prenylation.

 

PhD Project 3: Biologically relevant biomarkers of prostate cancer risk and disease outcomes

Supervisor: Prof Vanessa Hayes and Co-supervisor: Dr Eva Chan 

Prostate cancer is not only the most common male cancer worldwide (affecting one in every six men) it is arguably the most heritable of the common cancers. Australia has one of the highest incidence rates, with marked global disparities in both incidence and mortality. The genetic etiology of prostate cancer and this global (ethnic) disparity is however poorly understood. Clinical management is hindered by lack of reliable biomarkers and the heterogenous nature of disease course (from asymptomatic to rapid metastasis and mortality). The goal of this PhD study is to apply high-throughput genome-wide genetic approaches (from genotyping to sequencing) to identify biologically relevant (statistically significant) biomarkers of PCa that may explain disparities in prostate cancer risk and disease outcomes globally, using large local and internationally relevant study cohorts. The genetic data will furthermore be correlated with environmental factors to identify confounding associations, while biological relevance will be further investigated using both computational and laboratory-based models.

 

Honours Project 1: Transcriptional Profiling of Dormant Prostate Cancer Cells in the Skeleton

Supervisor: Prof Peter Croucher

Bone imagingProMis is an international collaboration of 7 research laboratories from across Australia and the US, led by Prof Croucher. ProMis aims to deliver transformative insights into the biology and heterogeneity of prostate cancer bone metastasis and develop new therapeutic approaches to preventing prostate cancer develop in the skeleton.

We have developed new labelling technology and intravital, two-photon imaging to visualise dormant prostate cancer cells in the skeleton in real time. PCa cells are labelled with a membrane dye (Vibryant DiD), which is shared between daughter cells when cells divide. Cells that do not proliferate retain the label and are therefore dormant. We wish to determine whether LNCaP and C4-2B prostate cancer cells are retained in a dormant state in bone and have a unique transcript profile when compared to proliferating cells. Specifically we will:

  1. Determine whether LNCaP and C4-2B cells are retained in a dormant state in bone.
  2. Determine whether all or only a limited number of LNCaP and C4-2B PCa are retained in a dormant state in bone.
  3. Purify dormant and proliferating PCa cells from bone and perform RNASeq.
  4. Establish a transcriptional signature for dormant LNCaP and C4-2B in the skeleton.

In this project the successful student will gain skills in animal models of metastasis, cell culture and two photon intravital imaging, in FACS sorting, RNASeq and bioinformatics analysis.

For more information please email: promis@garvan.org.au