SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in li ....Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in lipid bodies and its availability for phagocytosis, based on preliminary data showing such defects in the staggerer mouse model. Notably, cholesterol dysregulation is now a prevalent condition in society and our results will reveal at a fundamental, molecular level how this might compromise immune defenses.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.
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
Tolerising Antigen-specific Immunotherapy For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,395,549.00
Summary
We have developed a new immunotherapy to treat the underlying causes of type 1 diabetes (T1D) while leaving the rest of the immune system intact. To use this in patients, we need better tests to know when immune therapy is working. We will develop new methods to design the therapy and tools to track the relevant immune cells in T1D that work in variable patient groups. The knowledge gained will speed the pace of development and increase the chance of success of immunotherapy in T1D.
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
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.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
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
Moonlighting from sugar to metal. This project intends to use integrated genetics, biochemistry and omics to decipher the roles of the highly conserved OST3 proteins, which have been implicated in the disparate functions of regulating protein glycosylation and transporting magnesium. The project plans to detail the role of OST3 proteins in regulating mammalian glycosylation and reconstruct the vertebrate co-evolutionary trajectory of OST3 protein–substrate interactions. It also aims to identify ....Moonlighting from sugar to metal. This project intends to use integrated genetics, biochemistry and omics to decipher the roles of the highly conserved OST3 proteins, which have been implicated in the disparate functions of regulating protein glycosylation and transporting magnesium. The project plans to detail the role of OST3 proteins in regulating mammalian glycosylation and reconstruct the vertebrate co-evolutionary trajectory of OST3 protein–substrate interactions. It also aims to identify and characterise the regulation, mechanisms and metabolic consequences of OST3 protein-mediated magnesium transport. These outcomes may provide insights into eukaryotic biology, and allow advances in engineered systems for glycoprotein production and modulating cellular metabolism with potential research and therapeutic utility.Read moreRead less