Development Of New Therapy For Children Suffering From Epidermolysis Bullosa
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
Skin blistering diseases affect 1:17,000 live births. Constant skin blistering affects the quality of life and is often fatal in the first 2 years. For those children that survive, skin blistering leads to scarring, fusion of the fingers, infections and skin cancers. To date, the management of blistered children is mainly supportive and no specific cure exists. This study will develop new therapies for children with skin blistering diseases and will significantly improve their quality of life.
The Role Of SKAM And Sphingosine Kinase In Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$281,340.00
Summary
Many aspects of wound healing are poorly understood. We have identified a novel cellular pathway that appears critically involved in controlling wound contraction. This project aims to characterise this cellular pathway to understand the exact mechanisms whereby it controls this critical aspect of wound healing. With this information we will develop topical therapeutics to aid the wound healing process.
Regulation Of Epithelial Migration By Scribble In Development And Wound Repair
Funder
National Health and Medical Research Council
Funding Amount
$516,078.00
Summary
The movement of epithelial cells within our body (the cells that form the thin protective layer on exposed bodily surfaces such as skin and the lining of internal cavities, ducts, and organs) is essential for our normal embryonic development as well as for healing of wounds following injury. Understanding how this movement is regulated is therefore a fundamental area of medical biology. Although much is known about the mechanics of how a cell moves, the signals used to coordinate this movement s ....The movement of epithelial cells within our body (the cells that form the thin protective layer on exposed bodily surfaces such as skin and the lining of internal cavities, ducts, and organs) is essential for our normal embryonic development as well as for healing of wounds following injury. Understanding how this movement is regulated is therefore a fundamental area of medical biology. Although much is known about the mechanics of how a cell moves, the signals used to coordinate this movement so as to ensure that each cell migrates to the right place during embryonic development or in response to a wound is not well understood. A number of lines of evidence suggest that proteins required for the correct orientation of cells within our body (a property of cells known as polarity) may be essential for this process. Mutation of the polarity protein Scribble in the fly, zebrafish and mouse causes a disorganization of epithelial tissues during embryonic development. We have now shown that Scribble is required for cells to orientate correctly so as to be able to move in response to a wound in tissue culture and also during embryonic development and wound healing in the mouse. It is currently unknown how Scribble regulates migration. Here we propose to identify the molecules that Scribble regulates to coordinate cell movement during development and tissue repair. These studies will provide new insights into the fundamental process of how cell movement is coordinated and could lead to novel strategies for improved treatment of tissue injuries.Read moreRead less
Understanding The Regulation Of Cell Polarity In Development And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$428,602.00
Summary
Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have now shown that the gene Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we will examine how disruption of Scribble and associated molecules affects normal development and promotes cancer using a combination of tissue culture studies and a newly established mouse model. These studies may provide novel targets for therapeutic intervention in cancer.
Role Of The Tetraspanin CD151 In Epithelial Biology And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
A cell surface protein identified in this laboratory has been linked to cancer progression and metastasis. This project aims to examine the molecular basis of the action of the protein in regulating cell migration, and to establish model systems to provide definitive evidence as to its role in the development and progression of cancer. The models will also provide systems for future studies to evaluate the potential of antibodies and other inhibitors of the action of this protein as therapeutics ....A cell surface protein identified in this laboratory has been linked to cancer progression and metastasis. This project aims to examine the molecular basis of the action of the protein in regulating cell migration, and to establish model systems to provide definitive evidence as to its role in the development and progression of cancer. The models will also provide systems for future studies to evaluate the potential of antibodies and other inhibitors of the action of this protein as therapeutics in a range of human cancers.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
Integrin Intracellular Transport, Expression And Function In Macrophages Regulates Inflammation During Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$434,134.00
Summary
Burns are one of the most common and devastating forms of trauma; 70% occur in young children. Burns scars may be aesthetically disfiguring and functionally disabling, as well as psychosocially damaging. The study will identify how macrophages enter, function and persist in a burn wound to regulate inflammation, which if prolonged results in delayed healing and excess scar formation, and will generate multiple targets for potential future wound healing therapies.
Improving The Pre-hospital Treatment And Acute Management Of Burned Children
Funder
National Health and Medical Research Council
Funding Amount
$359,942.00
Summary
Children’s burns are physically and psychologically debilitating and are a huge burden for the children themselves, their families and the Australian health care system. My work will determine exactly what conditions are required to cause burns so that we can act to prevent them. I will also develop more effective first aid treatment and new treatments to improve burn wound healing.
This project aims to improve the acute treatment of children with burn injuries through developing more effective and novel treatments and understanding the conditions required for burn injuries to occur.
Development Of Monoclonal Antibody Therapy For Treating Wounds
Funder
National Health and Medical Research Council
Funding Amount
$573,354.00
Summary
Chronic wounds, diabetic ulcers, injuries in response to trauma, burns and scalds form a medical need which will only expand as the population ages and the diabetic epidemic grows. In our studies, we have shown that Flightless I (Flii), an actin-remodelling protein, is a negative regulator of wound healing. We are developing monoclonal antibodies as a new therapy for reducing Flii levels in wounds which leads to improved wound repair outcomes.