Identification Of Novel ERBB2 Co-operating Tumor Suppressors Using In Vivo RNAi Screens.
Funder
National Health and Medical Research Council
Summary
Invasive breast cancer is often lethal, however, noninvasive disease has a >98% survival rate. Thus, understanding how breast cancer develops invasive ability is an important research goal. Using a new method in mice predisposed to breast cancer, we will find genes that prevent tumor invasion and determine if they are important in human cancer. By understanding how these genes restrict tumor invasion, we hope to develop therapies to improve breast cancer treatment.
Testing Novel Therapies Using Paediatric Brain Tumour Models
Funder
National Health and Medical Research Council
Funding Amount
$384,023.00
Summary
Brain tumours are the second most common childhood cancer, with 300 children affected in Australia each year. Many children with brain tumours continue to die of their disease, whilst survivors are often left with devastating life long side effects. Our goals are to harness the power of innovative model systems of childhood brain tumours, in order to test the effectiveness of new treatments for these devastating diseases, so that the most promising therapies can be taken through to the clinic.
Targeted Molecular Therapies And Predictive Biomarkers In A Novel Orthotopic Xenograft Model Of Oesophageal Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
Oesophageal cancer is the most rapidly increasing malignancy in Western society. This disease often presents in advanced stages with poor response to established medical and surgical therapies. Our aim is to develop a novel mouse model of oesophageal cancer, allowing us to tailor cancer-inhibiting molecular treatments to individual patients by predicting therapeutic success or resistance with the use of cellular markers identified in our animal mode.
Regulation Of Mitogenic Signalling Via The Gab2 Docking Protein
Funder
National Health and Medical Research Council
Funding Amount
$141,750.00
Summary
Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. F ....Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. Furthermore, we have identified that another protein, termed PKB, can 'switch off' signalling by Gab2, and that deregulated signalling by Gab2 can make cells cancerous. The aim of this project is to characterize how PKB regulates Gab2, and to investigate whether this mechanism is impaired in human cancers, leading to enhanced Gab2 signalling. The research will provide important information regarding how growth factor signals are transmitted inside cells, and may identify a new cancer-causing gene.Read moreRead less
REVEALING MOLECULAR MECHANISMS OF THE SYNCHROTRON RADIATION-INDUCED BYSTANDER EFFECT
Funder
National Health and Medical Research Council
Funding Amount
$429,294.00
Summary
Radiotherapy, a major treatment for more than half of cancer patients, is based on the dogma that radiation kills targeted cells. The radiation-induced bystander effect, by which the neighbours of irradiated cells can also damaged, is a new paradigm. What is the "danger signal" which induces DNA damage in un-irradiated normal tissues, and what minimal volume of tissue needs to be irradiated to induce bystander damage? The answers could have a major impact on optimising radiotherapy treatment.
Activated Protein C Suppresses The Abnormal Immune Response In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
This project will determine whether activated protein C (APC) reduces the severity of rheumatoid arthritis (RA) by altering the abnormal response of a type of white blood cells known as the T cells. Experiments will utilise T cells isolated from patients with RA, normal controls and an animal model of RA, to examine a newly discovered immune pathway now thought to play a major role in causing RA. The results will help clarify whether and how APC prevents joint destruction in RA
T Cells: Their Impact On HIV Evolution And Their Regulation In Influenza
Funder
National Health and Medical Research Council
Funding Amount
$338,484.00
Summary
The T cells of our immune system are critical defenders against viral infection. It is vitally important to understand what stimulates these cells so we can better target them against globally important viruses, such as HIV and influenza - infections that kill millions per year. We need to understand what genes in the T cell turns them into effective killers and which part of these viruses elicits the most effective T cell response. We can use this knowledge for vaccine development.
Last year an estimated 3.1 million people died of AIDS (source: UNAIDS, Dec 2002) equivalent to the number killed by tuberculosis and malaria combined. AIDS-related opportunistic infections (OIs) are the main cause of death for AIDS patients, especially in resource constrained countries where access to antiretroviral and antibiotic therapy is limited. Attempts to limit the epidemic have failed and new foci have emerged in Eastern Europe, Central Asia and, of particular relevance for us, South Ea ....Last year an estimated 3.1 million people died of AIDS (source: UNAIDS, Dec 2002) equivalent to the number killed by tuberculosis and malaria combined. AIDS-related opportunistic infections (OIs) are the main cause of death for AIDS patients, especially in resource constrained countries where access to antiretroviral and antibiotic therapy is limited. Attempts to limit the epidemic have failed and new foci have emerged in Eastern Europe, Central Asia and, of particular relevance for us, South East Asia, underlining the fact that safe and effective treatment for AIDS-related OIs will be a global health priority for the foreseeable future. People with healthy immune systems do not get OIs since the germs that cause such infections are efficiently ingested and subsequently destroyed by cells called macrophages. We have discovered that the virus that causes AIDS, HIV-1, interferes with the ability of macrophages to ingest opportunistic pathogens by the 2 most important mechanisms used for this purpose. We believe that this is the direct cause for the susceptibility of AIDS patients to many of the opportunistic pathogens that cause their OIs. The purpose of this grant will be to understand the biochemical basis underlying these 2 defects in macrophage function. This will help in the design of safe, adjunctive therapies aimed at improving macrophage function and reducing the risk of HIV-infected individuals developing AIDS-related OIs.Read moreRead less
Evaluation Of Immune Correlates For Virus-specific CD8+ T Cells Following Prime-boost Vaccination
Funder
National Health and Medical Research Council
Funding Amount
$397,889.00
Summary
This project will use cutting-edge technology to evaluate the quality of virus-specific white blood cells generated following vaccination. Clinically relevant vaccination strategies will be analysed in a well characterised mouse model of infection to produce correlates associated with protective vaccine efficacy, particularly in an immunosupressed setting. This will lead to more focused research and ultimately the development of prophylactic and therapeutic HIV vaccines.