Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of di ....Navigating tipping points in complex dynamical systems. This project aims to use applied mathematics to investigate the onset of tipping points in dynamical systems. Working with clinicians and practicing engineers, the project aims to contribute to the development of new treatment regimes for dynamical diseases and develop improved management strategies for resource focussed engineering industries. This should provide significant benefit to many areas, including the personalised treatment of disease.Read moreRead less
The Role And Underlying Mechanisms Of Constitutional Epigenetic Silencing In Cancer Predisposition
Funder
National Health and Medical Research Council
Funding Amount
$218,617.00
Summary
Familial and young onset bowel and uterine cancer are usually caused by the inheritance of spelling mistakes in the genetic code within a set of cancer-protection genes. Recently, some patients were identified with their gene switched off by paralysing chemicals instead. This study aims to identify additional cancer cases with gene paralysis, determine if this arises in the presence or absence of a genetic change in front of the gene, and how gene paralysis is transmitted to the next generation.
Validation Of A Multiplexed Blood Based Screening Assay For The Diagnosis Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$556,712.00
Summary
Colorectal cancer (CRC) is the second most common cancer in Australia with poor patient outcome due to late detection of the disease. We have developed a simple blood based test that can diagnose individuals with CRC at an early stage when the chance of cure is greater than 80%.
Molecular Characterisation Of Early Precursor Lesions Of A Novel Ñserrated Pathwayî Of Colorectal Cancer Using Gene Expression And Proteomics.
Funder
National Health and Medical Research Council
Funding Amount
$318,338.00
Summary
In Australia, CRC is the second highest cause of all cancer-related deaths. If detected early, CRC has a high success rate of cure, but a percentage of precursor lesions escape detection and show aggressive clinical behaviour to progress to CRC. These are difficult to diagnosis with existing technologies. We aim to understand the biology behind sessile serrated adenoma pathways and hence enhance early detection, diagnosis and treatments strategies.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
Prognosis based network-type feature extraction for complex biological data. This project aims to develop statistical tools that integrate high-throughput molecular data with biological knowledge to make discoveries in complex diseases. This project uses machine learning methods, statistical models and proteomic platforms to identify relationships among clinico-pathologic and molecular measurements. It will produce tools and insights that are intended to accelerate the process of biologically an ....Prognosis based network-type feature extraction for complex biological data. This project aims to develop statistical tools that integrate high-throughput molecular data with biological knowledge to make discoveries in complex diseases. This project uses machine learning methods, statistical models and proteomic platforms to identify relationships among clinico-pathologic and molecular measurements. It will produce tools and insights that are intended to accelerate the process of biologically and clinically significant discoveries in biomedical research. This project will help Australian researchers in statistics and users of statistics (from fields as diverse as biology, ecology, medicine, finance, agriculture and the social sciences) to make better predictions that are easier to understand.Read moreRead less
Understanding the Chemical Processes Involved in the Metabolism of Peptide Hormones. Peptide hormones regulate normal physiological activity in humans, and their over-production causes diseases such as cancer. The aims of this project are: to delineate the chemical processes through which these hormones are produced; to develop inhibitors of enzymes involved in hormone production, and agonists and antagonists of receptors through which the hormones act; and to study the ability of the inhibitors ....Understanding the Chemical Processes Involved in the Metabolism of Peptide Hormones. Peptide hormones regulate normal physiological activity in humans, and their over-production causes diseases such as cancer. The aims of this project are: to delineate the chemical processes through which these hormones are produced; to develop inhibitors of enzymes involved in hormone production, and agonists and antagonists of receptors through which the hormones act; and to study the ability of the inhibitors, agonists and antagonists to override and bypass the chemical control mechanisms through which hormone levels are usually maintained at homeostasis. The research is expected to lead to a better fundamental understanding of hormone metabolism, and to underpin the basis for the development of new disease therapies.Read moreRead less