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
Cell Surface Mucins In Gastrointestinal Infection, Inflammation And Cancer Development
Funder
National Health and Medical Research Council
Funding Amount
$469,627.00
Summary
Cell surface mucins are protective molecules that line all the wet surface of the body, including the gastrointestinal tract. Our research has uncovered that mucins regulate cell growth and cell death. Inappropriate control by the mucins, could lead to chronic inflammation and formation of cancers. We will test how important these molecules are in the development of cancers in the intestine, and further explore the mechanism of action.
Evolution And Function Of A Novel Lateral Flagellar Locus, Flag-2, In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$465,158.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified a novel genetic region that allows E. coli to survive and persist in the intestine. Similar genes are also present in closely related organisms. This project will help us to undestand how new diseases evolve and emerge and may lead to the development of new vaccines to protect against infant diarrhoea.
This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to dev ....This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to develop more effective and selective treatments ofchronic inflammatory disease in humans.Read moreRead less
In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak protein is a member of the Bcl-2 family of apoptosis regulators, and plays a pivotal role in mediating cell death. By defining each step in Bak-mediated apoptosis, we aim to better understand how cancer cells accumulate, and how targeting the Bcl-2 family may lead to effective anti-cancer therapeutics.
Role Of Bak And Bax Membrane Anchors In Targeting And Apoptotic Pore Formation.
Funder
National Health and Medical Research Council
Funding Amount
$352,319.00
Summary
In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak and Bax proteins are members of the Bcl-2 family of apoptosis regulators, and play a pivotal role in mediating cell death. By defining how these proteins form a pore in mitochondria, the point of no return in cell death, will help the development of novel anti-cancer agents that target the Bcl-2 family in general, and Bak and Bax in particular.
ASPREE-D; Aspirin In The Prevention Of Depression In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$796,784.00
Summary
The ASPREE (ASPirin in Reducing Events in the Elderly) study is a 5 year RCT of aspirin (100mg daily) or placebo in 19,000 healthy people over 70. We aim to augment the existing infrastructure of ASPREE in order to confirm the utility of aspirin for the prevention of depression in the elderly (ASPREE-D). The primary aim of ASPREE-D is to determine if use of low-dose aspirin reduces the incidence of de-novo episodes of depression in healthy individuals over 70 years of age.
Imaging Neutrophil And Endothelial Function In Acute Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$545,517.00
Summary
The glomerulus is a group of small blood vessels which form the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response during which white blood cells accumulate in the glomerular blood vessels and cause damage. In this project, we will visualise the blood vessel lining of the glomerulus in order to understand how white blood cells damage this region and cause leakage of protein leak into the urine.
Inflammation of the kidneys is an important, yet poorly understood cause of kidney disease in Australia. This project will define the role of some of the immune cells, called Th17, that usually act to protect us from infection, but can turn rouge and may cause kidney damage.
TLR9 AGGRAVATES GLOMERULONEPHRITIS AND KIDNEY INJURY IN RENAL VASCULITIS
Funder
National Health and Medical Research Council
Funding Amount
$349,336.00
Summary
Renal failure is a significant cause of morbidity and mortality in Australia. Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis associated glomerulonephritis (GN) is a significant cause of renal failure. The molecular mechanisms underlying ANCA vasculitis are poorly understood, while treatments are associated with considerable morbidity and mortality. This grant aims to explore key molecular events involved in the disease pathogenesis to facilitate the use of safer more targeted therapies.