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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
Apoptosis And Stem Cells In Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$22,852,198.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks: enhanced cell survival and stem cell-like behaviour. As we discovered, cell death is often blocked in cancer cells. Hence, we are attempting to develop drugs that flip the natural ‘cell death switch’. Stem cells are rare cells that generate entire tissues, as we showed for the breast. Certain cancers may be driven by ‘rogue’ stem cells. If so, eradication of these rare cells within the bulk tumour may require novel therapies.
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.
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. P ....New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. Plastic is present everywhere in human life, but its manufacture and disposal have a strong negative impact on the environment; the new materials manufactured in this project are viable alternatives to plastics, and are sustainable from a production and disposal point of view.Read moreRead less
Tibet's rivers in the Anthropocene: history and present trajectories. This project aims to produce a multifaceted history of the eastern Tibetan Plateau's rivers, focusing on the increasing human impacts during the Anthropocene. It will combine data from archival, cultural and oral sources in multiple languages with the results of scientific studies of river flow, water quality, and sediment, ice, and tree-rings analysis. The project will produce both historical narratives and graphic representa ....Tibet's rivers in the Anthropocene: history and present trajectories. This project aims to produce a multifaceted history of the eastern Tibetan Plateau's rivers, focusing on the increasing human impacts during the Anthropocene. It will combine data from archival, cultural and oral sources in multiple languages with the results of scientific studies of river flow, water quality, and sediment, ice, and tree-rings analysis. The project will produce both historical narratives and graphic representations that model past land and water usage. The results of the project will underpin environmental policy for this hydrologically and ecologically crucial region, including the development of a paradigm of care based on the region's indigenous cultural resources.Read moreRead less
The culture of weeds: invasion biology, identity and aesthetics in Australia. Weeds are a significant threat to Australia’s biodiversity - but when does a plant become one? Defining plants and landscapes as weedy reflects not only ecological values, but also economics, aesthetics, and national identity. The question of how and why weeds spread reveals cultural values that inform the management of all invasive species.
Understanding the role of trauma in alcohol and other drug-related problems. This project aims to investigate the relationship between trauma and alcohol and other drug (AOD)-related problems. Using a robust set of qualitative and ethnographic methods, the project expects to advance international knowledge on how experiences of trauma influence AOD consumption, and the diverse factors that shape variation in experience and outcomes for individuals. Expected outcomes include targeted recommendati ....Understanding the role of trauma in alcohol and other drug-related problems. This project aims to investigate the relationship between trauma and alcohol and other drug (AOD)-related problems. Using a robust set of qualitative and ethnographic methods, the project expects to advance international knowledge on how experiences of trauma influence AOD consumption, and the diverse factors that shape variation in experience and outcomes for individuals. Expected outcomes include targeted recommendations to improve AOD responses, policy and trauma-informed AOD care, and increased capacity of the Australian health workforce to respond to trauma and AOD-related problems. This should provide significant benefit by reducing the harms, and economic and social costs associated with AOD consumption.Read moreRead less