For 60 years, we have had only 3 effective cancer treatments: surgery, radiation and chemotherapy, often used in combination.The last 5 years have produced a powerful fourth treatment: the patient's own immune system.The long standing collaborations and synergies of our multi-disciplinary teams have already underpinned many recent advances in immune-based therapies: we are now poised to develop several further immunotherapies and on track to test them in patients during the term of this grant.
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
Using MiR-200 To Find New Therapeutic Targets For Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$563,152.00
Summary
Neuroblastoma is one of the most common cancers in children. We have found that a genetic regulator, called microRNA, can limit the ability of neuroblastoma cells to invade surrounding tissues and metastasise. We aim use the microRNAs to find new therapeutic targets that may work in combination with existing treatments, reducing the short term toxicity and long term deleterious effects of current treatments.
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.
Engineering MYCN Models Of High-grade Serous Ovarian Cancer (HGSC)
Funder
National Health and Medical Research Council
Funding Amount
$797,478.00
Summary
The most lethal type of ovarian cancer, high-grade serous cancer (HGSC), can be divided into four subtypes based on gene patterns. One subtype involves a set of genes/proteins that, in their specific combination, result in activation of a pathway known as MYCN. As most HGSC start in the fallopian tube, we are using fallopian tube material to make new MYCN HGSC models to observe development in the earliest stages. We hope to generate new tests and treatments for this subtype of ovarian 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.
Role Of MACROD2 Loss In DNA Repair, Chromosomal Instability And Development Of Colorectal Cancer: Clinical And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$772,871.00
Summary
The MACROD2 gene is deleted in one-third of human bowel cancers. We have discovered that MACROD2 deletion causes defective DNA repair and tumour chromosomal instability. Here, we will use novel laboratory models to show that MACROD2 loss actively promotes bowel cancer development. We will test the clinical implication of MACROD2 loss for predicting tumour therapy response and will investigate the potential of exploiting this deficiency for drug targeting.
Determination of cellular mechanisms underpinning cancer cell metastasis through integrated in vivo imaging approaches. Understanding key steps that drive the spread of cancer is critical to improve current treatment strategies. Using cutting-edge imaging technology and in vivo model systems that mimic the disease, this project will pinpoint key events that are susceptible to drug intervention and identify new therapeutic targets.
How do mechanical cues regulate tissue renewal and tumour progression? Imbalances between cell production and cell death in tissues can be catastrophic, leading to major global health issues such as cancer. This project will use modified mice and protein-protein interaction based techniques to identify how changes in the mechanical properties of tissues regulate the balance between cell production and cell death.
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.