Control of immune recognition and response by microbial metabolites. This project aims to study immune recognition of microbial metabolites and develop reagents to control immune responses. Chemical synthesis will be used to develop new antigens for unconventional T cells and the first soluble agonists and antagonists of a glycolipid-sensing immune receptor. Expected outcomes include the discovery of new immune effectors, broadening our knowledge of the repertoire of small molecules that can be ....Control of immune recognition and response by microbial metabolites. This project aims to study immune recognition of microbial metabolites and develop reagents to control immune responses. Chemical synthesis will be used to develop new antigens for unconventional T cells and the first soluble agonists and antagonists of a glycolipid-sensing immune receptor. Expected outcomes include the discovery of new immune effectors, broadening our knowledge of the repertoire of small molecules that can be sensed by the immune system, and developing chemical approaches to promote or dampen immune responses. Major benefits include research training in chemical biology, strengthened international linkages and fundamental insights into the chemical basis of immune recognition and response.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100162
Funder
Australian Research Council
Funding Amount
$374,005.00
Summary
Enzymatic synthesis of pro-resolution lipid mediators: Towards new therapeutic strategies for inflammatory diseases. Inflammation is a major contributing factor in many diseases, including arthritis, Alzheimer's disease, multiple sclerosis, cardiovascular disease and cancer. It has recently been shown that the resolution of inflammation is an active biological process initiated by lipid mediators. The aim of this project is to synthesise and characterise pro-resolution lipid mediators, elucidate ....Enzymatic synthesis of pro-resolution lipid mediators: Towards new therapeutic strategies for inflammatory diseases. Inflammation is a major contributing factor in many diseases, including arthritis, Alzheimer's disease, multiple sclerosis, cardiovascular disease and cancer. It has recently been shown that the resolution of inflammation is an active biological process initiated by lipid mediators. The aim of this project is to synthesise and characterise pro-resolution lipid mediators, elucidate the enzyme cascades involved in their biosynthesis and explore their roles in the active resolution of inflammation. This project will provide a fundamental understanding of pro-resolution and anti-inflammatory pathways as well as new therapeutic target molecules for the treatment of inflammatory diseases.Read moreRead less
Unravelling the immunology of complex glycolipids by chemical synthesis. This project seeks to develop new approaches to chemically synthesise bacterial and fungal glycolipids and develop a molecular-level understanding of their effect on the immune system. Bacterial and fungal glycolipids are exotic chemical species that act as danger signals to prime and modulate our innate immune responses. These complex glycolipids possess powerful immunological activities that continue to shape our understa ....Unravelling the immunology of complex glycolipids by chemical synthesis. This project seeks to develop new approaches to chemically synthesise bacterial and fungal glycolipids and develop a molecular-level understanding of their effect on the immune system. Bacterial and fungal glycolipids are exotic chemical species that act as danger signals to prime and modulate our innate immune responses. These complex glycolipids possess powerful immunological activities that continue to shape our understanding of innate immunity, yet cannot be acquired from natural sources in the quantities and purity needed. The approaches expected to be developed in the project will be used to illuminate molecular details of immune signalling through pattern recognition receptors and presentation on specialised glycolipid antigen-presenting molecules. Outcomes may include new ways to fight disease and promote health by marshalling the resources of the immune system.Read moreRead less
Lymphotropic prodrugs: a novel mechanism for targeted drug delivery. This project aims to design chemically modified drugs that target drug delivery specifically to white blood cells. This approach promises to maximise drug action and simultaneously reduce toxicity for diseases where lymphocytes are the major drug target. These include autoimmune disease, leukaemia, lymphoma, HIV, transplant rejection and diabetes.
New platform technologies for the chemical synthesis of post-translationally modified proteins. The last decade has seen an explosion in the number of protein drugs approved for use in the clinic, a large proportion of which possess post-translational modifications (PTMs). These modified protein drugs are produced and sold as mixtures which has led to difficulties in understanding the role of specific PTMs on activity and in gaining clinical approval for candidate drugs. This project will provid ....New platform technologies for the chemical synthesis of post-translationally modified proteins. The last decade has seen an explosion in the number of protein drugs approved for use in the clinic, a large proportion of which possess post-translational modifications (PTMs). These modified protein drugs are produced and sold as mixtures which has led to difficulties in understanding the role of specific PTMs on activity and in gaining clinical approval for candidate drugs. This project will provide a fundamental solution to this problem through the development of novel synthetic methods and a powerful new platform technology for accessing PTM proteins in pure form. The utility of this technology will be demonstrated through its use in the total chemical synthesis of a range of PTM proteins for applications in biology and medicine.Read moreRead less
Characterisation of nanobubbles. Surprisingly, nano-sized bubbles have recently been found to exist in aqueous solutions. Classical theory tells us they should rapidly dissolve, yet they are stable for several days, a phenomenon which has only recently been explained. Despite this, nanobubbles are already used in cleaning processes and appear to have significant health benefits. They are being investigated in treatments for asthma and neurodegenerative diseases. In collaboration with a pharmaceu ....Characterisation of nanobubbles. Surprisingly, nano-sized bubbles have recently been found to exist in aqueous solutions. Classical theory tells us they should rapidly dissolve, yet they are stable for several days, a phenomenon which has only recently been explained. Despite this, nanobubbles are already used in cleaning processes and appear to have significant health benefits. They are being investigated in treatments for asthma and neurodegenerative diseases. In collaboration with a pharmaceutical company, the best means to produce and characterise nanobubbles will be investigated, as well as the conditions governing their stability. The project also aims to determine how the nanobubbles interact with surfaces in order to better control their properties and achieve a better understanding of these bubbles.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100172
Funder
Australian Research Council
Funding Amount
$330,000.00
Summary
Comprehensive cell imaging facility. This facility will provide Australian biological science researchers with equipment for in-depth analyses of cell function in vitro and in vivo. It will enable innovative research targeted at important questions in fields including cancer, immunology, stem cell biology, infectious disease and tissue regeneration.
Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by buil ....Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by building on international collaborations, providing significant benefits to the health of the community and potential to develop innovative applications in biomedical industries.Read moreRead less
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
Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contr ....Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contribute to the development of new generation vaccines and therapies to protect against tissue-specific infectious diseases, cancers and autoimmune diseases.Read moreRead less