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
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology t ....Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets is mandated by humanity, and also to safeguard Australia's region against the social and economical implication of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
microRNAs and the control of T lymphocyte differentiation, function and malignant transformation. The molecular mechanism of the immune system is not completely understood. This project will investigate how transcription factors and microRNAs, two major types of regulatory molecules work together to control immune responses. The results from this research will assist in the design of better vaccination strategies and treat certain lymphomas.
Biogenesis of red blood cell membrane modifications by the malaria parasite Plasmodium falciparum. Malaria is not only a major global health problem, but also affects countries neighbouring Australia like Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (aid and military personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identi ....Biogenesis of red blood cell membrane modifications by the malaria parasite Plasmodium falciparum. Malaria is not only a major global health problem, but also affects countries neighbouring Australia like Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (aid and military personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for Plasmodium falciparum infection. Developing novel targets is mandated by humanity, but also to safeguard Australia's region against the social and economic implications of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preven ....Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preventative health perspective, the investigation of platelet calcium signalling will greatly accelerate the development of new pharmaceuticals to tackle acute and chronic cardiovascular diseases, such as stroke, heart attack and artherosclerosis. Read moreRead less
Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum- ....Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum-chemical methods and then test predictions experimentally. We will capitalise on our previous successful studies of Rubisco by addressing emergent issues which are the keys to understanding catalytic efficiency and CO2/O2 selectivity: the roles of a carbamylated lysine; the way CO2 addition is rendered irreversible; and the spin inversion inherent in O2 addition.Read moreRead less
Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This k ....Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This knowledge will reveal how IPO5 controls formation of sperm by revealing what other proteins it binds to and how this affects cell signaling and responses to the environment.
Benefits: This will provide information about potential interventions to control fertility or to repair abnormal cells.
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ARC Centre of Excellence in Plant Energy Biology. We propose a novel approach to improve sustainable yield by optimising the overall efficiency of energy capture, conversion and use by plants. Efficiency gains in metabolism, transport, and development will be more effective than optimising single nutrient inputs or product outputs. Improving multiple parameters simultaneously is a necessary solution to the increasing demand for more crop yield from finite land, water, and nutrient resources. Unp ....ARC Centre of Excellence in Plant Energy Biology. We propose a novel approach to improve sustainable yield by optimising the overall efficiency of energy capture, conversion and use by plants. Efficiency gains in metabolism, transport, and development will be more effective than optimising single nutrient inputs or product outputs. Improving multiple parameters simultaneously is a necessary solution to the increasing demand for more crop yield from finite land, water, and nutrient resources. Unpredictable environmental challenges adversely affect plant growth and further perturb plant energy balance, limiting yield. The epigenetic controls, gene variants and signals discovered will provide a new basis for sustainable productivity of crops and will future-proof plants in changing climates.Read moreRead less