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Characterisation Of The Cellular Changes Induced By Ultraviolet A Radiation
Funder
National Health and Medical Research Council
Funding Amount
$448,500.00
Summary
Sunlight is an important environmental health hazard as it causes immunosuppression and cancer. It suppresses our ability to destroy developing cancers. Australia has the highest incidence of skin cancer in the world, 66% of Australians develop skin cancer during their lifetime. The relationship between UV dose, wavelength and cancer in humans is unknown. As this cannot be directly experimentally determined in humans, surrogate biological endpoints such as immunosuppression will help determine t ....Sunlight is an important environmental health hazard as it causes immunosuppression and cancer. It suppresses our ability to destroy developing cancers. Australia has the highest incidence of skin cancer in the world, 66% of Australians develop skin cancer during their lifetime. The relationship between UV dose, wavelength and cancer in humans is unknown. As this cannot be directly experimentally determined in humans, surrogate biological endpoints such as immunosuppression will help determine the damaging wavebands within sunlight. There has been little work on the effect of UVA on health or the mechanisms of action of UVA compared to UVB. A recent consensus UVA working group of 80 international participants convened by the American Academy of Dermatology out of concern about the lack of knowledge of UVA on human health concluded that the action spectrum for photocarcinogenesis and photoageing, particularly the efficacy of UVA in humans remains to be elucidated, and that more funding should be provided for radiation biology research to help elucidate UVA mechanisms of injury. Similarly a recent expert meeting (including Prof. Halliday) convened by the International Agency for Research on Cancer (WHO) on sunscreen protection from skin cancer recommended that studies should be conducted on the effects of exposure to UVA in causing both photoageing and skin cancer which followed from their major recommendation that it is important to understand the nature of the dose-response relationship on risk and the action spectrum for each effect . The studies described in this project will contribute to these recommendations.Read moreRead less
Developmental Potential Of Murine Keratinocyte Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
The stem cells of the epidermis or outer lining of the skin are an important group of cells with a role in normal cell replenishment, in wound healing and in skin disorders such as psoriasis and cancer. These primitive cells remain in the skin during the lifetime of an individual and are responsible for the production of mature, functional cells that form a protective barrier against the environment and pathogens. We have recently developed a strategy for the isolation of stem cells of the skin ....The stem cells of the epidermis or outer lining of the skin are an important group of cells with a role in normal cell replenishment, in wound healing and in skin disorders such as psoriasis and cancer. These primitive cells remain in the skin during the lifetime of an individual and are responsible for the production of mature, functional cells that form a protective barrier against the environment and pathogens. We have recently developed a strategy for the isolation of stem cells of the skin which places us in a unique position to further study these cells and determine possible therapeutic approaches for the future. The aims of this project encompass testing the potency of skin stem cells (i) to reform complex structures such as a mature epidermis, hair follicles and sebaceous glands; and (ii) to give rise to cells from other tissues such as muscle and liver. A final aim of this project is to dissect the complexity of the stem cell compartment further to gain insights into how normal skin growth is regulated.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
Pre-clinical Evaluation Of Nano-membrane Dressings To Promote Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$188,600.00
Summary
This project will investigate whether a novel type of wound dressing can promote faster wound healing and reduce scarring. Time taken to heal is one of the best predictors of whether a wound will heal with significant scarring. The faster wounds heal the better. We have identified a new dressing with specific nano-scale pores that may promote faster healing. This dressing will be tested in the best model of human wound healing with the potential to progress to clinical trials if successful.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100050
Funder
Australian Research Council
Funding Amount
$1,681,491.00
Summary
A national network for magnetic resonance spectroscopy. Our proposed network of high-end facilities for solid-state nuclear magnetic resonance spectroscopy aims to establish cutting-edge capabilities nationally for molecular and materials characterisation. The new infrastructure will enable advanced studies in chemistry, drug design, materials science, and environmental sciences. The expected outcomes include new discoveries, innovative applications, and potential commercialisation of new produc ....A national network for magnetic resonance spectroscopy. Our proposed network of high-end facilities for solid-state nuclear magnetic resonance spectroscopy aims to establish cutting-edge capabilities nationally for molecular and materials characterisation. The new infrastructure will enable advanced studies in chemistry, drug design, materials science, and environmental sciences. The expected outcomes include new discoveries, innovative applications, and potential commercialisation of new products, which will bring significant economic benefits to the Australian economy. Additionally, the network will foster collaborations with international researchers and industry partners in areas of biotechnology, energy capture and storage, and environmental sustainability.Read moreRead less
Activated Protein C As A Promoter Of Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$391,650.00
Summary
The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physi ....The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physiological anticoagulation. APC potently activates gelatinase A, an enzyme that plays a prominent role during the remodelling phase of wound healing and angiogenesis. Our preliminary experiments provide very strong evidence that APC accelerates wound healing using both cultured cells and a rat skin wounding model. There are three aims to this study. The first will use cell culture techniques to investigate the mechanisms of action of APC during wound healing. Secondly, we will expand our pilot studies on the effect of APC as a promoter of wound healing in vivo. These studies will examine the exact dosing and timing regime for APC, using a rat wound healing model. In addition, we will test the effect of APC on slow healing wounds, present in diabetic rats. Thirdly, we will determine whether APC is quantitatively or functionally deficient in human wound fluid derived from slow-healing wounds compared to wounds that heal normally. This is the first time that APC has been implicated in wound healing. It is envisaged that this work will ultimately lead to a novel topical treatment of APC to accelerate slow-healing wounds.Read moreRead less
Defects In Epidermal Morphogenesis In Grainyhead-like Gene Deficient Mice
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
The cells of the skin play an essential role in the development of the mammalian embryo. They are critical for forming a protective barrier against infection and external toxins, for preventing excess fluid loss, for repair of defects and wounds , and for the generation of hair. Our laboratory has identified a family of genes that are critical for these processes. The aim of this study is to determine the relationship between these genes to further our understanding of the skin and its functions
The Role Of Dermal Mast Cells In Limiting The Pathology Associated With Chronic Low-dose UVB Irradiation Of The Skin.
Funder
National Health and Medical Research Council
Funding Amount
$513,945.00
Summary
Australians are subject to high levels of sun exposure , that consequently can lead to skin damage and skin cancer. The specific aims of our reseearch are to investigate the role of skin mast cells in the limitation of skin alterations associated with chronic low-dose ultraviolet B exposure. Understanding the innate mechanisms that protect against excessive skin damage and cancer might aid the development of better treatment modalities in the future.