Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
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.
Microenvironments which support extramedullary hematopoiesis. Tissue regeneration is a breakthrough technology absolutely dependent on knowledge of the stem cells and stromal cells which support differentiation and tissue development. This project investigates the stromal cell types in spleen which can regenerate blood-forming cells in an ectopic tissue site or artificial matrix.
Epigenetic reprogramming of development by nutritional factors in honeybee. The project aims to study the mechanism by which a specialised nutrition can change or even reverse the process of adult cell fate. The project will use a previously unexplored method of nutritional reprogramming of imaginal discs in honeybees by royal jelly and identify novel components of both the genetic and epigenetic systems that are most potent as reprogramming factors. The project seeks to improve our understandin ....Epigenetic reprogramming of development by nutritional factors in honeybee. The project aims to study the mechanism by which a specialised nutrition can change or even reverse the process of adult cell fate. The project will use a previously unexplored method of nutritional reprogramming of imaginal discs in honeybees by royal jelly and identify novel components of both the genetic and epigenetic systems that are most potent as reprogramming factors. The project seeks to improve our understanding of how epigenetic remodelling of the information content of the genome contributes to conversion of cell fate in vivo and in vitro. More broadly, the project could potentially establish the honeybee imaginal discs as a model for understanding pluripotency and environmentally controlled developmental plasticity.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100011
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, ....Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, biochemical and chemical probes with a focus on minimizing phototoxicity. Expected outcomes include new fundamental knowledge on molecular signal transduction and cell heterogeneity; development of novel probes and methodologies and the development of new and existing interdisciplinary research collaborations. Read moreRead less
Gamete-specific knockout of Fizzy-Related to examine its meiotic role in oocytes and sperm. Fizzy-Related is a gene that appears to be essential in making an ovulated egg, and it may also have an important role to play in making sperm. A mouse knockout will be generated to examine exactly how it functions; because it affects the egg number remaining in the ovary and egg quality Fizzy-Related may be eventually an important therapeutic target.
Multi-object Estimation for Live-Cell Microscopy. The objective of this project is to develop new tools for the inference of biological information from live-cell data to facilitate analysis of experiments and speed up discovery in cell biology. The new tools would provide reliable, consistent inference requiring no manual intervention and able to process large volumes of data in a timely manner. This would equip biologists with a vehicle that could move them closer to the goal of understanding ....Multi-object Estimation for Live-Cell Microscopy. The objective of this project is to develop new tools for the inference of biological information from live-cell data to facilitate analysis of experiments and speed up discovery in cell biology. The new tools would provide reliable, consistent inference requiring no manual intervention and able to process large volumes of data in a timely manner. This would equip biologists with a vehicle that could move them closer to the goal of understanding the mechanism behind biological processes.Read moreRead less
Role of Musashi in the regulation of cell cycle proteins. We have identified a protein family that directs cell fate and maintains male fertility. This project will provide new avenues for generation of contraceptives in male animals and to regulate stem cells for production of specialised cell types in biotechnological applications.
How ribosomal protein loss affects cell fate. This project aims to challenge the dogma that the ribosome behaves only as a ‘‘house-keeper’’. Ribosomal protein (RP) mutations should, and often do, result in reduced cell growth and stunted animal development. Depletion of RPs in Drosophila blood cells impair stem cells and cause massive tissue overgrowth. This suggests RPs are involved in cell fate determination, which this project will research using genetic models. As ribosomal function is funda ....How ribosomal protein loss affects cell fate. This project aims to challenge the dogma that the ribosome behaves only as a ‘‘house-keeper’’. Ribosomal protein (RP) mutations should, and often do, result in reduced cell growth and stunted animal development. Depletion of RPs in Drosophila blood cells impair stem cells and cause massive tissue overgrowth. This suggests RPs are involved in cell fate determination, which this project will research using genetic models. As ribosomal function is fundamental to the development of all living organisms, this work could have wide implications for understanding all biology – from microbes, insects and plants to humans.Read moreRead less