Broad spectrum nanomedicine for Meningitis treatment. Brain inflammatory diseases are among the top ten infectious causes of death. The project aims to provide Australian doctors with a superior alternative of treating infections that do not respond to conventional antibiotics. The nanomedicine developed will reduce the burden of hospital and boost Australia economy in the biomedical sector.
The Role Of Keratin End-domains In Filament Biology
Funder
National Health and Medical Research Council
Funding Amount
$139,235.00
Summary
The skin is the largest organ in the body and is the main interface between the organism and the external environment. It protects us from UV radiation, microbial invasion and chemical attack. It is able to repair itself and in fact, is continually renewing itself. In this study, we propose to examine the biology of keratins and the filament networks they form. Keratins are the most abundant proteins present in the epidermis, the outer layer of the skin. Keratins form a cellular skeleton that re ....The skin is the largest organ in the body and is the main interface between the organism and the external environment. It protects us from UV radiation, microbial invasion and chemical attack. It is able to repair itself and in fact, is continually renewing itself. In this study, we propose to examine the biology of keratins and the filament networks they form. Keratins are the most abundant proteins present in the epidermis, the outer layer of the skin. Keratins form a cellular skeleton that reinforces skin cells to help them withstand mechanical trauma. Mutations in these proteins result in a much weaker skeleton and ultimately in disease. We will examine how the keratin building blocks are transported around the cell to where they are needed. We will also determine the effect of mutations in this transport process on the biology of the cell. These studies may provide important clues into certain inherited skin disorders.Read moreRead less
New data-driven mathematical models of collective cell motion. Cancer and chronic wounds are a national, and indeed, international health problem set to worsen as our population ages. Predictive and interpretive tools are required to improve our understanding of collective cell migration in relation to cancer and chronic wounds. This project will produce new validated mathematical tools for predicting collective cell migration in a general framework that can deal with application-specific detail ....New data-driven mathematical models of collective cell motion. Cancer and chronic wounds are a national, and indeed, international health problem set to worsen as our population ages. Predictive and interpretive tools are required to improve our understanding of collective cell migration in relation to cancer and chronic wounds. This project will produce new validated mathematical tools for predicting collective cell migration in a general framework that can deal with application-specific details, such as the role of cell shape and cell size. Although cell shape and size are known to affect collective cell migration, standard mathematical models ignore these details. This project will produce new predictive mathematical modelling tools that are validated by new experimental data. Read moreRead less
Modelling cell invasion incorporating the epithelial to mesenchymal transition: Exploring therapies to control wound healing and cancer progression. Cancer and wounds are closely related, commonly lethal, diseases. Both require cell growth and invasion. This project will apply experimental measurements to create new mathematical models of cancer and wounds; models that will inform new targets and strategies for the treatment of these deadly diseases.
Human skin equivalent constructs: enhanced culturing and application of laboratory-grown skin through mathematical modelling and in silico experimentation. Laboratory-grown human skin equivalent constructs, given social and legislative imperatives, will be critical for advances in novel treatment protocol definitions for wound repair, dermatogical screening of pharmacueticals and fundamental studies of skin diseases.
In silico studies undertaken in this project will make a significant contrib ....Human skin equivalent constructs: enhanced culturing and application of laboratory-grown skin through mathematical modelling and in silico experimentation. Laboratory-grown human skin equivalent constructs, given social and legislative imperatives, will be critical for advances in novel treatment protocol definitions for wound repair, dermatogical screening of pharmacueticals and fundamental studies of skin diseases.
In silico studies undertaken in this project will make a significant contribution to the effectiveness of the application of human skin constructs, by delivering new and deeper insights into the interplay between dependent processes that regulate the behaviour of skin, in vivo or ex vivo. The models and the researchers associated with this project will drive innovative studies in medical science over the next decade.Read moreRead less
Mast Cells Determine Susceptibility To Induction Of Systemic Immunomodulation By UVB Radiation
Funder
National Health and Medical Research Council
Funding Amount
$194,993.00
Summary
The ultraviolet B component of sunlight causes an immunosuppression in humans such that UV-induced tumours develop. In a murine model, we have shown that dermal mast cells at the irradiated site are crucially important in the mechanisms by which UVB stimulates this immunosuppression. In this project we wish to study in more depth the mechanisms by which sunlight stimulates mast cells to produce molecules which in turn signal immunosuppressive events. We hypothesise that there is an intermediary ....The ultraviolet B component of sunlight causes an immunosuppression in humans such that UV-induced tumours develop. In a murine model, we have shown that dermal mast cells at the irradiated site are crucially important in the mechanisms by which UVB stimulates this immunosuppression. In this project we wish to study in more depth the mechanisms by which sunlight stimulates mast cells to produce molecules which in turn signal immunosuppressive events. We hypothesise that there is an intermediary by which sunlight stimulates mast cell activity; we hypothesise that cis-urocanic acid may be involved directly or indirectly in this process. There is considerable evidence that histamine may be the major product of mast cells involved in this process; however it is unknown whether its primary action is on keratinocytes (stimulating prostanoid production), antigen presenting cells or lymph node cells. This project will also investigate the relationship of studies with mice to UVB-induced systemic immunosuppression in humans. Non-sun-exposed skin from controls and patients with non-melanoma skin cancers will be examined and dermal mast cell prevalence evaluated; we hypothesise that people with high dermal mast cell numbers are more prone to immunosuppression and thus, the outgrowth of UV-induced non-melanoma skin cancers. We hypothesise that there may also be qualitative differences in the mast cells of UV-sensitive and UV-resistant individuals; variations may occur in the granule contents of neutral proteinases or cytokines. It is necessary that we better understand the basis of immune system modulation by UVB that allows non-melanoma skin cancer development as these patients have a 20-30% higher risk of death from other cancers.Read moreRead less
Biomaterials with multifaceted tunability and bio-specificity. Polyurethanes, a family of polymers with independently tunable mechanical and biodegradation properties, will be developed as a versatile platform material for biomedical implants. Novel energetic ion treatments that allow the coupling of bioactive agents to surfaces will eliminate adverse reactions and enable integration with surrounding tissue.
Cellular And Molecular Mechanisms Of Transcutaneous Immunisation
Funder
National Health and Medical Research Council
Funding Amount
$190,490.00
Summary
Vaccines are among the most effective medical interventions. The recent discovery that cholera toxin, when applied to the normal skin of humans and laboratory animals, stimulates powerful and protective immune responses to itself, and to other proteins has opened up the possibility of needle-free vaccines in the form of skin patches. How CT brings about this effect is currently unknown. We have discovered that the immune stimulating effect of CT depends upon the production of an immune protein ( ....Vaccines are among the most effective medical interventions. The recent discovery that cholera toxin, when applied to the normal skin of humans and laboratory animals, stimulates powerful and protective immune responses to itself, and to other proteins has opened up the possibility of needle-free vaccines in the form of skin patches. How CT brings about this effect is currently unknown. We have discovered that the immune stimulating effect of CT depends upon the production of an immune protein (cytokine) called tumour necrosis factor (TNF). TNF is known to activate specialised immune cells within the skin (Langerhan's Cells ) and we hypothesise that the interaction beween CT and LC via TNF is the pathway to the potent immune response. In this project we propose to investigate the cells and molecules involved in the immune effects of CT in the skin with a view to the development of new skin based vaccine strategies.Read moreRead less
MOLECULAR APPROACHES TO OVERCOME SCABIES AND ASSOCIATED DISEASE. Scabies causes childhood pyoderma predisposing to severe disease in later life. It is a major increasing health burden in Indigenous people of Northern Australia. Drug resistance is developing in mites and bacteria. The lack of clinical material has hampered molecular research and this work will use comparative genomics of parasitic and free living mites and microbiome analysis to understand fundamental aspects of mite biology and ....MOLECULAR APPROACHES TO OVERCOME SCABIES AND ASSOCIATED DISEASE. Scabies causes childhood pyoderma predisposing to severe disease in later life. It is a major increasing health burden in Indigenous people of Northern Australia. Drug resistance is developing in mites and bacteria. The lack of clinical material has hampered molecular research and this work will use comparative genomics of parasitic and free living mites and microbiome analysis to understand fundamental aspects of mite biology and pathogenesis. The understanding of proteins that are essential for mite survival and interfere with host defences will allow the informed design of peptide inhibitors as a new strategy to develop alternative treatment options.Read moreRead less
Inflammatory skin disorders, such as psoriasis and dermatitis, are responsible for a large burden of human disease and affect people across alldemographics. Knockout (KO) of TNF signalling members in mice is known to induce skin inflammation. This project proposes to use these genetic mouse models to investigate how and why disruption of particular TNF superfamily members leads to disease and potentially identify new targets for treatment.