Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases includ ....Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases including infectious disease, auto-immune disease and leukaemia, and thus a long-term outcome may be improved treatments for such disease. Read moreRead less
Structure and function of novel macrophage proteins using high throughput crystallography. We will combine the cutting edge technologies of microarray analysis and high throughput crystallography in an innovative approach to study the structure and function of important and uncharacterised macrophage proteins. Our strategy for targeting novel macrophage proteins will maximise the success rate of structure determination, while at the same time focusing our efforts on proteins that are important i ....Structure and function of novel macrophage proteins using high throughput crystallography. We will combine the cutting edge technologies of microarray analysis and high throughput crystallography in an innovative approach to study the structure and function of important and uncharacterised macrophage proteins. Our strategy for targeting novel macrophage proteins will maximise the success rate of structure determination, while at the same time focusing our efforts on proteins that are important in macrophage biology. Structures of the novel proteins will underpin functional analysis at a molecular level and could represent a basis for inhibitor design should the proteins ultimately be shown to be therapeutic targets.Read moreRead less
Proteomics Analysis of Interactions Between Chaperonin 10 and Cell Surface Proteins. Specific interactions at the cell surface may induce downstream biological responses. In the case of chaperonin 10, Cpn10, interaction at the cell surface results in immunomodulation of the inflammatory response. Cell surface proteins that interact with Cpn10 have not been identified. This project will use chemical crosslinking and proteomic techniques to identify cell surface proteins that interact with Cpn10 a ....Proteomics Analysis of Interactions Between Chaperonin 10 and Cell Surface Proteins. Specific interactions at the cell surface may induce downstream biological responses. In the case of chaperonin 10, Cpn10, interaction at the cell surface results in immunomodulation of the inflammatory response. Cell surface proteins that interact with Cpn10 have not been identified. This project will use chemical crosslinking and proteomic techniques to identify cell surface proteins that interact with Cpn10 and structural features of Cpn10 involved in these interactions. These findings will providde leads for the development of immunomodulatory therapeutics based on Cpn10 interactions. Analytical technologies will be developed that are applicable to other interacting protein systems.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989436
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Multiphoton microscopy of living animals as a tool for immunology and cell biology studies. The multiphoton microscope will enable us to watch the growth, migration and interactions of cells in a living animal in response to changes in the cells' environment will give us better understanding of how we work as living machines, and what can go wrong with that process to make us unwell.
The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of ....The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of macropinocytosis at a molecular level. The project is relevant to understanding the functioning of normal cells and the means by which some pathogens can enter cells and also understanding processes involved in tumour progression and metastasis.Read moreRead less
The development of tyrosine kinase inhibitors for the treatment of inflammation and malignant disease. Through the combination of expertise from the Industry partner and the Hume group this project aims to develop specific inhibitors of the CSF-1 receptor protein tyrosine kinase in order to demonstrate their efficacy as modulators of CSF-1 dependent macrophage and tumour cell function in vitro. The expected outcome will be a lead set of targets which can be further assessed for therapeutic pote ....The development of tyrosine kinase inhibitors for the treatment of inflammation and malignant disease. Through the combination of expertise from the Industry partner and the Hume group this project aims to develop specific inhibitors of the CSF-1 receptor protein tyrosine kinase in order to demonstrate their efficacy as modulators of CSF-1 dependent macrophage and tumour cell function in vitro. The expected outcome will be a lead set of targets which can be further assessed for therapeutic potential in clinical trials.Read moreRead less
Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology ....Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology, Ca2+ regulation and optical membrane potentiometry allow us to monitor early changes in disease on a (sub)cellular level. Experiments on Ca2+ regulation and ion channel function in muscle with different cholesterol membrane contents will help to understand pathomechanisms in high cholesterol diseases, e.g. obesity, on the membrane level long before cardiovascular effects become prominent.Read moreRead less
Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gat ....Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gathered much information about such epitopes, recent studies have shown that some unexpected regions of pathogens are targets for killer T cells. This project will break new ground by utilising unbiased procedures to assess the relative contribution of these noncanonical epitopes to immunity.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100150
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
Beyond Proteomics: structure and function of protein modifications. The world's leading cancer therapeutics have come from the protein phosphorylation field, and glycomics has led to drugs that combat the flu and that stimulate red blood cell production in cancer patients. Thus there is a bright future for discovery of new medicines based on new knowledge in this area. Protein modifications are key to the understanding of disease mechanisms and for searching for new disease markers and new the ....Beyond Proteomics: structure and function of protein modifications. The world's leading cancer therapeutics have come from the protein phosphorylation field, and glycomics has led to drugs that combat the flu and that stimulate red blood cell production in cancer patients. Thus there is a bright future for discovery of new medicines based on new knowledge in this area. Protein modifications are key to the understanding of disease mechanisms and for searching for new disease markers and new therapeutics. In the hands of local experts the instruments will enable identification of these modifications and provide improved understanding of biology, increase the national competitiveness of Australia's scientists, and provide advanced technology training to the next generation of scientists.Read moreRead less