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.
Proteome Analysis of Plant Response Pathways to Microbial Signals in the Model Legume, Medicago truncatula. This project will investigate plant responses to soil microbes in the model legume, Medicago truncatula, to provide fundamental information needed to design crops with improved abilities to interact beneficially with soil microbes. Plant development and performance are significantly influenced by soil microbes, but it is largely unknown how the information contained in microbial signalling ....Proteome Analysis of Plant Response Pathways to Microbial Signals in the Model Legume, Medicago truncatula. This project will investigate plant responses to soil microbes in the model legume, Medicago truncatula, to provide fundamental information needed to design crops with improved abilities to interact beneficially with soil microbes. Plant development and performance are significantly influenced by soil microbes, but it is largely unknown how the information contained in microbial signalling molecules is relayed to plants. Proteome analysis and immunocytochemistry will be combined to identify and localise differentially expressed proteins in roots treated with specific microbial signal molecules. Annotated Proteome databases will be generated to strengthen and complement an international project on M. truncatula genome analysis.Read moreRead less
Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less
Novel cell wall genes ripe for the picking. This project aims to investigate the role of recently discovered plant cellulose synthase-like CslM genes and to define the polysaccharide product associated with them. Successful identification of the polysaccharide is highly likely to increase our fundamental understanding of how cell walls are made, how cells stick together or fall apart as well as facilitating the training of the next generation of cell wall biologists in challenging molecular and ....Novel cell wall genes ripe for the picking. This project aims to investigate the role of recently discovered plant cellulose synthase-like CslM genes and to define the polysaccharide product associated with them. Successful identification of the polysaccharide is highly likely to increase our fundamental understanding of how cell walls are made, how cells stick together or fall apart as well as facilitating the training of the next generation of cell wall biologists in challenging molecular and biochemical techniques. This new knowledge could increase our understanding of fruit ripening, and how it might be manipulated. This could have significant downstream commercial benefits if applied to breeding programs of economically important fruit such as grapes, tomatoes and strawberries.Read moreRead less
Environmental Influences In The Establishment Of The Epigenetic Landscape In Children
Funder
National Health and Medical Research Council
Funding Amount
$695,097.00
Summary
The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells ....The DNA in each of our cells does not exist alone, it is packaged into complex structures called chromosomes, through association with many different proteins. The distribution of these proteins varies along the length of a chromosome depending on the type of cell and this phenomenon is called 'epigenetics', literally meaning 'above the DNA'. Epigenetic analysis is the study of how proteins and other molecules can change the activity of a gene without changing the DNA sequence. All of our cells use epigenetic changes to help control how they grow and develop. Evidence suggests a direct link between diet and environmental influences on our epigenetic profile. Recent research has traced the origins of many of the health problems of adult life back to the earliest periods of development _ to the time spent in the womb and the first few years of life. If we are born with a low birth weight, we are more likely to get sick later in life. Overwhelming evidence exists that the environment in the womb is critical for a healthy birth weight (and health in later life) and it is thought that epigenetics may be the missing link between this environment, low birth weight, and therefore health in later life. In addition, mounting evidence supports a general link between epigenetic de-regulation and predisposition to disease. However, the timing and the overall contribution of environmental- genetic influences to the establishment of faulty epigenetic markings remain largely unknown. Twins are the best model to study this link as they share similar (but not identical environments) and some share identical genetic makeup. Using twins, Dr Jeffrey Craig and his team will investigate the factors in the prenatal environment that modify specific cells, leading to low birth weight and increase disease risk later in life. They predict that this occurs via specific changes in gene activity caused by epigenetic disruption.Read moreRead less
Predicting cell wall mechanics from structure in a materials engineering approach to plant growth. The project fosters a novel, interdisciplinary approach to understanding how the structure of plant cell walls determines their mechanical properties. Such understanding requires combining biological and engineering approaches and will illuminate how plants grow and produce cells and organs with particular shapes. This is scientifically important but is also important for industries depending on sp ....Predicting cell wall mechanics from structure in a materials engineering approach to plant growth. The project fosters a novel, interdisciplinary approach to understanding how the structure of plant cell walls determines their mechanical properties. Such understanding requires combining biological and engineering approaches and will illuminate how plants grow and produce cells and organs with particular shapes. This is scientifically important but is also important for industries depending on specialised cell shapes such as those of cotton and wood fibres. Our work will improve our understanding of how wall structure determines fibre and other cell shapes and give us tools which can be used to understand how final wall structure determines the fibre mechanics on which industrial users depend. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100210
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
In-vivo, high-resolution, whole animal imaging . The purchase of state-of-the-art live-animal imaging equipment for use by researchers at The Australian National University and The University of New South Wales. This equipment will aid the study of many aspects of normal biology and disease including cancer, inflammation, autoimmune diseases and blood vessel disorders.
New methods for structure analysis of proteins and protein interactions. This project will advance nuclear magnetic resonance (NMR) technologies pioneered at the Australian National University which employ site-specific attachment of paramagnetic metal tags to proteins. A new and diverse set of strategies will dramatically extend the range of applications to targets of interest in the fight against cancer and bacterial infections.