Dr Ricarda Thier

Selected research projects for HDR students:

GSTP1-1 Regulates Progression and Metastasis in Prostate Cancer: In 2013 about 20,000 men will be diagnosed with prostate cancer (PCa) and more than 3,300 men will die as a direct cause of this disease. When tumours turn malignant, they start to infiltrate the surrounding tissue and individual cancer cells migrate to other organs and generate a secondary tumour. Spread and Metastasis of cancer is the most important and least understood factor in disease progression to a malignant tumour. Emerging evidence suggests that tiny microvesicles, exosomes, are 'sent ahead' by primary tumours to prepare normal tissues for arrival of metastatic cells and establishment of metastases. Glutathione transferase GSTP1-1 has been identified as one of several tumour markers. GSTP1-1 protects normal cells from toxins, oxidative stress, inflammatory damage, and ultimately from early cancer development. In advanced tumours GSTP1 shelters tumour cells from drug treatment effects and promotes growth and migration properties. GSTP1-1 and other glutathione transferases have been found in exosomes of many different normal and cancerous tissues, indicating that GSTs indeed play a role in cell-cell communication and possibly in tumour invasion and metastasis.

This project aims to identify whether GSTP1-1 and other GSTs are also present in PCa generated exosomes and contribute to PCa progression locally and in bones, the major site of PCa metastasis.   Students will be exposed to a variety of techniques including advanced tissue culture, cytotoxicity assays, differential centrifugation, immunocytochemistry, RT-PCR and Western blots, apoptosis assays and timelapse-imaging.

Effects of Flame Retardants on Neurodevelopment: Brominated flame-retardants (PBDEs) are used widely in every day products particularly building materials, motor vehicles, (home) electronics and textiles. They bioaccumulate and our main uptake  is via the diet. Environmental exposure to PBDEs in Australia is amongst the highest in the world. Previous studies show that particularly 2-5 year old children show a high level of PBDEs in blood. Concern about their impact on healthy neurodevelopment arise from findings that prenatal exposure to PBDEs might be linked to mental development deficiencies in 2 and 5-6 year old children. Changes in behavioural and motor skills upon prenatal PBDE exposure have also been observed in animal studies.  This study investigates effects of flame retardants on

1. the outgrowth and morphology of axons from neurons and
2. the morphology and migration of Schwann cells in vitro. Comparison between newborn and adult mice will be performed.

The projectbased on primary cell cultures and introduces students to organic pollutants, their potential health effects in humans and offers experience in cell culture, immunocytochemistry and imaging techniques, such as isolation and growth of dorsal root ganglion neurons and Schwann cells from transgenic mice, neurite outgrowth assay using time-lapse live imaging, analysis of data with BD PathwayTM bioimaging platforms, and determination of subcellular adaptation via immunocytochemistry.

Enhancement of Antineoplastic Efficacy of Carmustine in Glioblastoma Chemotherapy:  Glioma is the most common brain cancer in adults but prognosis is very poor. Current treatment includes a combination of surgery, radiotherapy, and chemotherapy with e.g. carmustine (BCNU). The polymorphic drug metbaolising enzyme GSTT1-1 is readily inactivating carmustine. A gene deletion polymorphism in the GSTT1 gene leads to three phenotypes. In Caucasians 11-30 % are devoid of the GSTT1 gene. The remaining subpopulation is carrying either one or two copies of the gene resulting in intermediate or high enzyme activity, respectively. The two latter groups will have high capacity to inactivate carmustine. We hypothesise that high activity of GSTT1-1 reduces the antineoplastic efficacy of carmustine in glioma cells and, thus, contributing to the poor prognosis of glioma patients.

This study investigates whether the knock down of the GSTT1 gene with shRNA will enhance antineoplastic effects of carmustine in vitro. This project is based on cell culture. Techniques to be used include polymerase chain reaction (PCR), knock down of gene expression with shRNA, cell survival assays, Western blots and spectrophotometric enzyme activity assays.