Innovative Use Of Hydrogel Technology To Recapitulate And Investigate Cardiac Pathology.
Funder
National Health and Medical Research Council
Funding Amount
$716,162.00
Summary
Hypertrophic cardiomyopathy is the leading cause of sudden death in the young. No treatment exists that can reverse or prevent it, primarily because the underlying mechanisms of the disease have not been fully elucidated. I will use innovative hydrogel technology to simulate the disease state. I will use this as a tool to identify the mechanisms involved with development of the disease. This will enable identification of potential therapeutic targets for prevention of the disease.
Cytoskeletal Remodeling Of The Erythrocyte During Malaria Parasite Invasion
Funder
National Health and Medical Research Council
Funding Amount
$559,807.00
Summary
Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease ....Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease establishment.Read moreRead less
The Role Of The Actomyosin Cytoskeleton In T Cell-mediated Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$616,950.00
Summary
T cells, specialised immune cells, are crucial in the defence against tumours. In order to reach cancerous target cells, T cells must enter tumour tissues from the blood stream and then effectively migrate in the extravascular space. This application aims to uncover the role of the cytoskeleton, a group of molecules driving cell shape change and motility, in the efficient execution of T cell anti-tumour function. These studies will aid the development of improved immunotherapies against cancer.
Discovering New Pathways To Improved Biotherapeutic Treatment Of Snakebite Envenoming.
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Snakebite is a public health emergency affecting up to 5.4 million people a year, causing up to 125,000 deaths. This multidisciplinary project will develop a new generation of medicines for treating snakebites, using innovative design approaches supported by cutting edge science and novel production ideas. Directly focused on improving antivenom effectiveness in the treatment of snakebites in Australia, Africa and Papua New Guinea, the results will make Australia a world leader in this field.
Pharmacological Strategy For Blocking Lung Cell Damage By Toxic Smoke Constituents.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, ....People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, where the lung is flooded with fluids and is unable to perform its respiratory function. At present, the clinical approaches used to treat smoke inhalation victims are mostly directed against offsetting the symptoms of lung injury and do not take into account the role of lung cell injury by toxic substances in smoke such as acrolein. This project will provide a better understanding of the chemical events underlying the injury caused by smoke to lung cells, and also into possible drug strategies for treating victims of smoke inhalation. The work will explore the ability of a range of compounds that are chemically related to a blood pressure-lowering medicine (hydralazine) to protect lung cells against such smoke-induced damage. The work will employ a range of modern research techniques to understand the events occurring in lung cells exposed to smoke. Once this is understood, these approaches will be used to test the various drug compounds for their abilities to prevent the death of cells exposed to smoke or its toxic constutuent acrolein. This work will yield new information on a series of compounds concerning their ability to block the toxicity of smoke to lung cells. The goal is to identify one or two molecules that can be carried forward to testing in smoke-exposed animals.Read moreRead less
A Novel Cytoskeletal Structure In Muscle Is Associated With Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$371,250.00
Summary
A NEW PROTEIN NETWORK IN MUSCLE IS ASSOCIATED WITH MUSCLE DISEASE An intricate protein network connects the contracting mechanism of a muscle to the surrounding cell membrane. Disruption of this connection is one of the known causes of muscular dystrophy. For many patients however the cause of the disease is unknown. We have identified a new region within this protein network that is also associated with muscle disease in mice. A number of proteins that are involved in transmitting chemical mess ....A NEW PROTEIN NETWORK IN MUSCLE IS ASSOCIATED WITH MUSCLE DISEASE An intricate protein network connects the contracting mechanism of a muscle to the surrounding cell membrane. Disruption of this connection is one of the known causes of muscular dystrophy. For many patients however the cause of the disease is unknown. We have identified a new region within this protein network that is also associated with muscle disease in mice. A number of proteins that are involved in transmitting chemical messages from one part of the muscle cell to another are found at this same location. It is possible that disruption of these messages may lead to muscle disease. This project aims to establish the nature of the relationship between the proteins found in this newly identified region of the protein network and muscle diseases such as muscular dystrophy, in both animal models and in humans. We expect that this project may identify new markers for identifying the cause of muscle diseases in some patients and lead to better hopes for an eventual cure.Read moreRead less
ISG60, A Novel Interferon-induced Protein: Cell Growth Inhibitory Actions
Funder
National Health and Medical Research Council
Funding Amount
$197,030.00
Summary
The interferons are signaling molecules produced by cells as part of an early warning sytsem to alert nearby tissue cells and immune cells to defend themselves against an impending viral attack or aberrant growth of cells. We have discovered ISG60, a new member of a group of proteins called the ISG54 family. The production of this family of proteins is turned on in all cells responding to the interferons. Exactly what the members of the protein family do within cells remains to be established. H ....The interferons are signaling molecules produced by cells as part of an early warning sytsem to alert nearby tissue cells and immune cells to defend themselves against an impending viral attack or aberrant growth of cells. We have discovered ISG60, a new member of a group of proteins called the ISG54 family. The production of this family of proteins is turned on in all cells responding to the interferons. Exactly what the members of the protein family do within cells remains to be established. However, by preparing cells which produce the ISG60 protein, we have found that it severely affects their growth, slowing the growth rate down and making the cells divide abnormally to become large, containing many nuclei and others dying. We propose that ISG60 binds to the structures involved in cell division and we have preliminary evidence that ISG60 interacts with an important protein involved in cell regulation, the retinoblastoma protein (pRb). The aim of this project is to more fully understand the role of ISG60 in cells. In particular, we aim to determine if ISG60 interacts with other important proteins inside cells. We shall explore the relationship of ISG60 function inside cells in greater detail as it should provide new insight into ways in which cell growth is regulated. This study will also provide insight into how the slowing of cell growth makes the cells less suitable for viral infection and reproduction, as well as providing new approaches for preventing the growth of cancer cells.Read moreRead less
Function Of The Flightless Protein In Wound Repair And Scar Formation In Skin
Funder
National Health and Medical Research Council
Funding Amount
$472,750.00
Summary
Scarring is the inevitable outcome of wound repair and can cover a spectrum of conditions, from normal fine lines to unsightly, restrictive and deforming scars. Each year in the world over 100 million patients acquire scars, primarily from surgical procedures. Many of these scars cause considerable problems. Over 4 million burn scars occur every year, 70% of them in children. Poor wound healing is a major clinical problem and can result in loss of movement and deformity. These are especially imp ....Scarring is the inevitable outcome of wound repair and can cover a spectrum of conditions, from normal fine lines to unsightly, restrictive and deforming scars. Each year in the world over 100 million patients acquire scars, primarily from surgical procedures. Many of these scars cause considerable problems. Over 4 million burn scars occur every year, 70% of them in children. Poor wound healing is a major clinical problem and can result in loss of movement and deformity. These are especially important considerations for children, where their growth places extra demands on healing wounds and grafts, necessitating regular surgical adjustment. Scarring is an area of largely unmet medical need and development of new treatment strategies would have significant impact on public health. Changes in cell adhesion, shape and movement are important processes in wound repair. A framework of filaments, much like guy-ropes that support a tent, help coordinate these events. Remodelling of these filaments, shortening or extending them and making new connections, allows cells to change shape and respond to stimuli. This is a crucial event in repairing wounds and the proteins that perform this are fundamentally important to wound repair. We have discovered a protein in skin, known as Flightless, that is involved in this filament remodelling process. The goal of this project is to determine what Flightless does in wound repair. By changing the amount of this protein and comparing its effect in non-scarring and scarring animal wound healing models we can gain insight into its role in wound healing and scar formation in humans. The development of new animal models in this research and the discovery of the role of Flightless in wound repair will provide exciting new opportunities to improve wound repair and reduce scarring, with significant impact on public health.Read moreRead less
Unified Model For Group A Streptococcal Invasive Disease Initiation.
Funder
National Health and Medical Research Council
Funding Amount
$605,221.00
Summary
Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis and streptococcal toxic shock-like syndrome. We have recently discovered the trigger mechanism for GAS invasive disease. We hypothesise that the initial host response at the site of infection selects for a GAS invasive phenotype. We propose to examine the chain of events which result in tissue invasion in order to unde ....Streptococcus pyogenes (group A streptococcus; GAS) is a bacterium that causes human skin and throat infections as well as highly invasive diseases including necrotising fasciitis and streptococcal toxic shock-like syndrome. We have recently discovered the trigger mechanism for GAS invasive disease. We hypothesise that the initial host response at the site of infection selects for a GAS invasive phenotype. We propose to examine the chain of events which result in tissue invasion in order to understand these disease processes and allow the development of future therapeutic interventions.Read moreRead less