Predicting Renal, Ophthalmic And Heart Events In The Aboriginal Community: The PROPHECY Diabetes Multi-Omics Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$3,955,505.00
Summary
Diabetes is at epidemic levels in Indigenous Australians, impairing quality of life, and contributing to poor health. This is a result of rapid development of kidney, heart and eye complications. We have established a large long-term population study among Aboriginal communities within South Australia and will explore the burden, natural history and the social, psychological, environmental, clinical and genomic predictors of diabetes and its complications.
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.
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.
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
Physiological and molecular controls of plant transpiration efficiency: investigating the role of the ERECTA gene. Water is the single most limiting factor in agriculture and the world's supply of fresh water is diminishing, the greatest fraction of total water use being by agriculture. Progress in water-use efficiency will have social value, and this program should help us to achieve it. Our progress in this area is already one of the most successful of 'bottom-up' approaches - in the sense of ....Physiological and molecular controls of plant transpiration efficiency: investigating the role of the ERECTA gene. Water is the single most limiting factor in agriculture and the world's supply of fresh water is diminishing, the greatest fraction of total water use being by agriculture. Progress in water-use efficiency will have social value, and this program should help us to achieve it. Our progress in this area is already one of the most successful of 'bottom-up' approaches - in the sense of transferring knowledge from biochemistry and biophysics to breeding and agronomy, as CSIRO now has a successful wheat breeding program based on this earlier work of ours. Now that we have discovered a gene that controls water-use efficiency at the leaf level, we wish to see how the gene works, and how it affects mineral nutrition of leaves.Read moreRead less
Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to ....Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to provide novel functions, thereby facilitating the evolution of specific characteristics within species.Read moreRead less
Cellular signals controlling oocyte activation. This research will significantly advance our understanding of the basic biological processes that underpin the fertility rate of all mammals and are key to the immediate and future health and well-being of Australian landscape and society. Understanding the processes that maintain healthy quiescent oocytes over many years before activation and subsequent growth will enable development of methods of increasing productivity in domestic animals and en ....Cellular signals controlling oocyte activation. This research will significantly advance our understanding of the basic biological processes that underpin the fertility rate of all mammals and are key to the immediate and future health and well-being of Australian landscape and society. Understanding the processes that maintain healthy quiescent oocytes over many years before activation and subsequent growth will enable development of methods of increasing productivity in domestic animals and enhancing fertility in endangered species. Knowledge of these cellular mechanisms will underpin biotechnology platforms necessary for novel methods of feral animal population control thus contributing at multiple levels to an economically sustainable Australia.Read moreRead less
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
The Shape of Plants; Discovering factors that control morphology by organizing the cytoskeleton. Understanding how plants generate the huge diversity of shapes seen in nature is both a scientific challenge and a biotechnological opportunity. Microtubules dominate cell architecture, providing dynamic, yet rigid, frameworks for defining or changing growth polarity. We recently discovered and cloned MOR1, a gene that is essential for organizing microtubules and controlling morphogenesis. This place ....The Shape of Plants; Discovering factors that control morphology by organizing the cytoskeleton. Understanding how plants generate the huge diversity of shapes seen in nature is both a scientific challenge and a biotechnological opportunity. Microtubules dominate cell architecture, providing dynamic, yet rigid, frameworks for defining or changing growth polarity. We recently discovered and cloned MOR1, a gene that is essential for organizing microtubules and controlling morphogenesis. This places us in a strong position to resolve a long-standing mystery: how are microtubules organized? We intend to define MOR1's structural attributes, identify its interacting proteins and innovate an ambitious screen for additional genes that have related functions. This project should stimulate new ideas and applications.Read moreRead less
CesA (cellulose synthase) genes of Arabidopsis; all doing the same job or specialists cooperating to make the most abundant biopolymer. The biosphere makes more cellulose than any other polymer with fibre industries depending on its physical properties and atmospheric carbon dioxide levels depending on its stability as a carbon sink. Demonstrations that cellulose production needs CesA genes drove recent progress in elucidating the mechanism of synthesis. CesA proteins all look very similar but i ....CesA (cellulose synthase) genes of Arabidopsis; all doing the same job or specialists cooperating to make the most abundant biopolymer. The biosphere makes more cellulose than any other polymer with fibre industries depending on its physical properties and atmospheric carbon dioxide levels depending on its stability as a carbon sink. Demonstrations that cellulose production needs CesA genes drove recent progress in elucidating the mechanism of synthesis. CesA proteins all look very similar but if all do the same job, why do plants need so many and why do none seem redundant? We will make gene interchanges in transgenic plants, build chimeric genes and identify where each CesA protein operates. This will identify their individual and cooperative contributions to cellulose production.Read moreRead less