Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883068
Funder
Australian Research Council
Funding Amount
$150,000.00
Summary
Dako ACIS III Cellular Image Acquisition and Analysis System. The scientific advances that will be possible with the acquisition of this novel, cutting-edge instrument will enhance the research outputs of all investigators using it. The ability to visualize and analyze cells and tissues from many different animal species, to elucidate both normal and abnormal functions, will be enhanced by the use of this technology. This will lead to production of quantitative statistical data that in turn will ....Dako ACIS III Cellular Image Acquisition and Analysis System. The scientific advances that will be possible with the acquisition of this novel, cutting-edge instrument will enhance the research outputs of all investigators using it. The ability to visualize and analyze cells and tissues from many different animal species, to elucidate both normal and abnormal functions, will be enhanced by the use of this technology. This will lead to production of quantitative statistical data that in turn will inform new approaches to improve and maintain the health of humans and other animals.Read moreRead less
Molecular Determinants Of Subcellular Localisation And Function Of The Transmembrane 4 Superfamily Protein, PETA-3
Funder
National Health and Medical Research Council
Funding Amount
$322,911.00
Summary
Several years ago we identified the cell membrane protein PETA-3-CD151 based on its ability to cause activation of blood platelets, suggesting a role in thrombosis. More recently we found that the protein is present in a variety of tissues, although its distribution in those tissues is often restricted. It is abundant in a variety of cancer cells, and is present on tissue mast cells that mediate allergic reactions. PETA-3-CD151 forms complexes with molecules (integrins) that are associated with ....Several years ago we identified the cell membrane protein PETA-3-CD151 based on its ability to cause activation of blood platelets, suggesting a role in thrombosis. More recently we found that the protein is present in a variety of tissues, although its distribution in those tissues is often restricted. It is abundant in a variety of cancer cells, and is present on tissue mast cells that mediate allergic reactions. PETA-3-CD151 forms complexes with molecules (integrins) that are associated with cell adhesion and migration, and antibodies to this protein inhibit cell movement. Thus PETA-3-CD151 appears to be involved in cellular interactions that are critical for normal tissue development and function, and may be involved in several disease processes including cancer invasion and metastasis. The molecular basis of PETA-3-CD151 function is not understood and is the focus of this application.Read moreRead less
Regulation Of Hedgehog Signalling Through Intracellular Trafficking Events
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
The hedgehog signalling cascade plays a role in forming almost every organ of the body during development of an embryo. Perturbation of the function of key members of this pathway during embryonic development often results in death in utero or severe childhood abnormalities. In addition, disruption to this pathway also results in a range of cancers, most notably the extremely common skin cancer basal cell carcinoma. In this proposal we aim to investigate in detail the regulatory mechanisms which ....The hedgehog signalling cascade plays a role in forming almost every organ of the body during development of an embryo. Perturbation of the function of key members of this pathway during embryonic development often results in death in utero or severe childhood abnormalities. In addition, disruption to this pathway also results in a range of cancers, most notably the extremely common skin cancer basal cell carcinoma. In this proposal we aim to investigate in detail the regulatory mechanisms which operate to ensure that this complex pathway of interacting molecules functions correctly during embryonic development. By understanding how this regulation occurs we will gain valuable insight into how disruption of this pathway results in such a range of disease, as well as into how agents which modulate this pathway may potentially act in a therapeutic setting.Read moreRead less
The roles of novel pathways in the activation and regulation of the adaptive immune response in health and disease. The immune system is designed to protect us against infection and vaccines exploit this with great success in preventing many infections. However, the immune system can also 'fail' and attack the body in a process called autoimmunity e.g. destroying joints in rheumatoid arthritis. This proposal will define how white blood cells work to make better vaccines against infection and ho ....The roles of novel pathways in the activation and regulation of the adaptive immune response in health and disease. The immune system is designed to protect us against infection and vaccines exploit this with great success in preventing many infections. However, the immune system can also 'fail' and attack the body in a process called autoimmunity e.g. destroying joints in rheumatoid arthritis. This proposal will define how white blood cells work to make better vaccines against infection and how these same immune cells can malfunction to create autoimmune diseases like Crohn's disease.Read moreRead less
Molecular, genetic and cellular analysis of melanisation in human pigmentation. This investigation examines variations in the genes that determine human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of ....Molecular, genetic and cellular analysis of melanisation in human pigmentation. This investigation examines variations in the genes that determine human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of the damaging effects of ultraviolet (UV) radiation. A better understanding of the genetic basis of UV-sensitive skin types will greatly enhance the targeting of such skin cancer-prevention campaigns, provide an understanding of changes that occur in skin pathology, and the mechanisms of sun induced tanning.Read moreRead less
Investigating The Physiological And Biochemical Role Of SOCS5 In The Immune System
Funder
National Health and Medical Research Council
Funding Amount
$405,940.00
Summary
Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against paras ....Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against parasite infection. In other words, asthma is thought to arise through inappropriate IL-4 and IL-13 activity in the absence of a parasite infection. Extra IL-13 is commonly found in the lungs of asthmatics and is thought to help trigger asthma attacks. IL-13 is a validated target for drugs that could be used in the treatment of asthma. The SOCS genes were discovered in our laboratory and by genetically deleting the genes in mice we have demonstrated a critical role for SOCS1, SOCS2 and SOCS3 in regulating the immune response and the action of growth hormone. My hypothesis is that SOCS5 is an important physiologic regulator of the asthma response. This proposal will investigate the basic biochemical processes underlying the regulation of IL-4 and IL-13 action and the relationship to development of asthma and immune disease. I plan to induce asthma attacks in mice that lack the genes for SOCS4 and SOCS5. If the severity of the attacks is greater in the absence of these proteins this will indicate that SOCS4 and-or SOCS5 are important negative regulators of IL-4 and IL-13. This has the potential to open up a completely new strategy for the development of drugs that could be used in the prevention and treatment of asthma.Read moreRead less
Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasi ....Combined genetic and cellular analysis of melanisation to study variation in human pigmentation. This investigation examines variations in the genes that are important determinants of human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of the damaging effects of UV radiation. A better understanding of the genetic basis of UV-sensitive skin types will greatly enhance the targeting of such skin cancer-prevention campaigns, provide an understanding of changes that occur in skin pathology, and the mechanisms of sun induced tanning.Read moreRead less
Parallel genetic and cellular analysis of melanogensis: A new paradigm to study variation in pigmentation. This is the first attempt to characterise the differences in human pigmentation using a combined genetic and cellular analysis of melanogenesis. We have the ability to culture the pigmenting cells of the human epidermis and hair follicles called melanocytes from individuals of defined genotype. This will allow us to correlate mutations in melanosomal proteins with functional defects withi ....Parallel genetic and cellular analysis of melanogensis: A new paradigm to study variation in pigmentation. This is the first attempt to characterise the differences in human pigmentation using a combined genetic and cellular analysis of melanogenesis. We have the ability to culture the pigmenting cells of the human epidermis and hair follicles called melanocytes from individuals of defined genotype. This will allow us to correlate mutations in melanosomal proteins with functional defects within the cells in culture using live cell imaging, electron microscopy and biochemical analysis. This will provide a molecular basis to explain the pigmentary characteristics of individuals allowing prediction and diagnosis of their photosensitivity with important implications for skin cancer risk.Read moreRead less
The role of palmitoylation in hair follicle and epidermal stem cell biology. A proteins activity can be shaped by sugar, phosphate and lipid modifications. This proposal will investigate the effects of the lipid modification called palmitoylation, about which we know very little. Our preliminary experiments suggest that palmitoylation is crucial for normal skin biology. We will explore its effects on the biology of the proteins which are modified, the cells in which they are found and the tis ....The role of palmitoylation in hair follicle and epidermal stem cell biology. A proteins activity can be shaped by sugar, phosphate and lipid modifications. This proposal will investigate the effects of the lipid modification called palmitoylation, about which we know very little. Our preliminary experiments suggest that palmitoylation is crucial for normal skin biology. We will explore its effects on the biology of the proteins which are modified, the cells in which they are found and the tissues in which they reside. Understanding more about these modifications will help us to learn more about the biology of our skin and will help us to understand diseases which affect our largest organ.Read moreRead less