Evaluation Of Molecular Mechanisms Driving Metastasis Using Integrated Intravital Imaging
Funder
National Health and Medical Research Council
Funding Amount
$885,271.00
Summary
Metastasis is the leading cause of cancer-associated death. Understanding key steps that drive the spread of cancer is critical to improve current treatment strategies. Using cutting-edge imaging technology and 3-dimensional model systems that mimic the disease, we will pinpoint key events that are susceptible to drug intervention and identify new therapeutic targets.
Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolut ....Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolution of live imaging to the single molecule to understand the dynamics of actin assembly with implications for cellular processes that are hijacked in diseases. It also aims to provide a novel assay that may enable testing of the impact of drugs on cellular processes in real time.Read moreRead less
Role of endocytic mechanisms in mammalian cytokinesis. Cell division requires endocytic proteins and failed cell division can contribute to cancer. This project aims to understand how endocytic proteins function to complete cell division successfully and has implications for the development of chemotherapeutic agents to treat cancer.
Real-time Optical Window Imaging Of AKT-FRET Biosensor Mice To Maximise PI3K/AKT Drug Targeting Within The Hypoxic Microenvironment Of Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$683,447.00
Summary
Inefficient drug response in solid tumour tissue is often a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours with low oxygen levels known as hypoxia. Here, we will specifically target factors limiting efficient drug targeting in these areas to improve the encouraging anti-cancer profile of AKT inhibitors in pancreatic cancer.
PARP And PI3K Inhibition In Pancreatic Cancer: Intravital Insights And ‘fine-tune’ Priming Using AKT And Single/double-strand DNA Break Biosensor Mice.
Funder
National Health and Medical Research Council
Funding Amount
$760,505.00
Summary
Inefficient drug response in solid tumour tissue is often a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we can map areas of poor drug response within distinct regions of tumours with chemotherapy. Here, we will shift factors limiting efficient drug targeting in these areas to improve the encouraging anti-cancer profile of PI3K and DNA repair inhibitors in pancreatic cancer.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100092
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Fluorescence microscopy with optical tweezers: imaging cellular responses. Life relies on the ability of our cells to receive and respond to signals with pinpoint accuracy, involving both chemical and mechanical signals. This equipment will allow scientists to expose cells to both types of signals and measure the response at an unprecedented level of accuracy for the first time.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100166
Funder
Australian Research Council
Funding Amount
$370,000.00
Summary
Imaging Cell and Tissue Architecture using Confocal and Super-Resolution Microscopy. Imaging cell and tissue architecture using confocal and super-resolution microscopy: This project aims to understand how the architecture of cells and tissues is controlled. This is because the organisation of biological space underpins the function of cells, tissues and organisms. This project will test the role of identified parts of cell architecture in regulating specific animal functions/pathologies. It wil ....Imaging Cell and Tissue Architecture using Confocal and Super-Resolution Microscopy. Imaging cell and tissue architecture using confocal and super-resolution microscopy: This project aims to understand how the architecture of cells and tissues is controlled. This is because the organisation of biological space underpins the function of cells, tissues and organisms. This project will test the role of identified parts of cell architecture in regulating specific animal functions/pathologies. It will do this by using new microscope technologies which are at the frontier of visualising cell structure in isolation and in the context of tissue including application to the living animal. The dynamic organisation of structures in cells will be imaged in living tissue. Novel insights into structure/function relationships in the body will impact the health industry and generate opportunities for new diagnostics and therapeutics. Read moreRead less
Identification of novel therapeutic targets for selectively eliminating cancer stem cells in paediatric leukaemia. Leukaemia is the most common form of cancer in children, and while the majority of children can be cured, those who relapse face a dire prognosis. It is widely believed that leukemic stem cells are responsible for relapse and this project will aim to unravel their underlying biology and identify new targets for therapeutic approaches to the disease.
mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patien ....mTOR signalling in serous ovarian cancer. Serous ovarian cancer is the most aggressive and lethal gynaecological cancer in Australian women. Activation of Mammalian Target of Rapamycin (mTOR) is frequently observed and associated with poor prognosis in ovarian cancer patients. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. In preliminary studies, deletion of genes regulating mTOR signalling in up to 60 per cent of human serous ovarian cancer patients was observed. This project will provide mechanistic details of involvement of mTOR signalling in pathogenesis of the serous ovarian carcinoma, and develop a rationale for targeting mTOR pathway in these patients. Read moreRead less
Targeting Bone Marrow Mediated Angiogenesis And Metastasis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,006.00
Summary
Despite advances in treatment and diagnostics breast cancer (BC) remains one of the leading causes of death in women. Metastases and tumour blood vessel recruitment are linked. Work by Dr Mellick and others has shown that host bone marrow contributes endothelial progenitor cells (EPCs) to tumour vasculature. The chemokines and their receptors, which differentiate EPCs from tumour vessels, will be knocked down in the tumour cells and EPC progenitors with the aim of preventing tumour spread.