Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
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.
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
TELEPHONE COUNSELLING FOR MAINTENANCE OF PHYSICAL ACTIVITY, WEIGHT LOSS And GLYCAEMIC CONTROL IN TYPE 2 DIABETES
Funder
National Health and Medical Research Council
Funding Amount
$1,285,894.00
Summary
Regular exercise, a healthy diet and weight loss are key to managing type 2 diabetes, yet these are major challenges for most people with diabetes. This study will evaluate the impact of a telephone counselling program to assist people with type 2 diabetes to exercise, eat a healthy diet and lose weight, with the goal of helping them to sustain these changes over the long-term. It is expected that these lifestyle changes will also result in improved blood glucose control and quality of life.
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.
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Understanding The Acute And Cumulative Metabolic Effects Of Prolonged Sitting In Adults
Funder
National Health and Medical Research Council
Funding Amount
$416,597.00
Summary
Sedentary behaviour (sitting time) has been linked to an increased risk of chronic illnesses, including type 2 diabetes and obesity, but recent evidence suggests that light-intensity activity (non-exercise activities of daily living) is associated with reduced risk. These studies will examine whether breaking up sitting time with frequent short periods of activity can overcome the negative effects of prolonged sitting on blood glucose and blood fats in overweight older adults.
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
Pathogen recognition and plant-defence activation by a novel Fusarium wilt-resistance protein from tomato. The devastating effects of Fusarium wilt disease of tomato is a threat to one of Australia's most economically important horticultural crops. Resistant tomato varieties offer the most effective means of control but the fundamental mechanisms underlying this resistance are yet to be understood. This research will increase our understanding of resistance to Fusarium wilt disease. The knowledg ....Pathogen recognition and plant-defence activation by a novel Fusarium wilt-resistance protein from tomato. The devastating effects of Fusarium wilt disease of tomato is a threat to one of Australia's most economically important horticultural crops. Resistant tomato varieties offer the most effective means of control but the fundamental mechanisms underlying this resistance are yet to be understood. This research will increase our understanding of resistance to Fusarium wilt disease. The knowledge gained will assist in the development of new robust, sustainable approaches to disease control, as well as the development of pre-emptive strategies to avert major outbreaks, which will ensure reliable productivity and minimal economic losses into the future.Read moreRead less
Translocation of secreted effector proteins from fungal pathogens into host plant cells. Every year, fungal diseases of plants cause huge losses in agricultural productivity and extensive environmental damage in Australia. Disease control in major crops, like wheat, currently relies heavily on breeding for disease resistance. However, fungal pathogens continually adapt to overcome plant defences, necessitating identification of new sources of resistance. The research in this project will eluc ....Translocation of secreted effector proteins from fungal pathogens into host plant cells. Every year, fungal diseases of plants cause huge losses in agricultural productivity and extensive environmental damage in Australia. Disease control in major crops, like wheat, currently relies heavily on breeding for disease resistance. However, fungal pathogens continually adapt to overcome plant defences, necessitating identification of new sources of resistance. The research in this project will elucidate the molecular basis of a new aspect of the establishment of plant infection by fungi, and in so doing will provide new avenues for the development of novel disease resistance strategies, with relevance in particular to devastating cereal diseases like wheat rust.Read moreRead less