Discovery Early Career Researcher Award - Grant ID: DE180101075
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Novel immune cell subsets in the centre nervous system and supporting tissues. This project aims to identify and characterise novel resident immune cell subsets within the brain and retina, and their close supporting tissues. The project expects to generate new knowledge in the areas of neuroimmunology and ocular immunology by using molecular and cellular techniques to examine the diversity of immune cells within the brain and retina. It is expected that the project will advance our understandin ....Novel immune cell subsets in the centre nervous system and supporting tissues. This project aims to identify and characterise novel resident immune cell subsets within the brain and retina, and their close supporting tissues. The project expects to generate new knowledge in the areas of neuroimmunology and ocular immunology by using molecular and cellular techniques to examine the diversity of immune cells within the brain and retina. It is expected that the project will advance our understanding of the biological mechanisms that protect the central nervous system from harmful inflammation and thus improve our knowledge of the immunobiology of the brain and eye.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
Machine learning for organelle selection & feature detection in live cells. This project aims to addresses a roadblock in cell imaging and analysis by creating new mathematical and machine learning techniques for large datasets. Using advanced imaging and these analytic tools this project aims to define newly-discovered macropinosomes - cell structures with seminal roles in immunobiology. Outcomes will include a suite of computational tools that can be applied across bioscience to fully reveal a ....Machine learning for organelle selection & feature detection in live cells. This project aims to addresses a roadblock in cell imaging and analysis by creating new mathematical and machine learning techniques for large datasets. Using advanced imaging and these analytic tools this project aims to define newly-discovered macropinosomes - cell structures with seminal roles in immunobiology. Outcomes will include a suite of computational tools that can be applied across bioscience to fully reveal and quantify information contained within microscopic imaging and high impact knowledge for immunity. Innovative approaches will benefit the nation by capacity building in interdisciplinary technology.Read moreRead less
Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM re ....Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM remodelling. Previous studies have developed a unique mouse model of childhood asthma and discovered the molecular mechanism by which this tissue tropism develops in response to virus infection. This project will identify new targets for immunomodulation and design new biologics to block ASM remodelling and the deleterious effects of respiratory virus infection in asthmatic subjects. Read moreRead less
A new approach to reversing and preventing immune-mediated diseases. Chronic inflammatory diseases affect up to 20 per cent of Australians. These diseases reduce wellbeing and life potential and shorten lifespan. This project addresses the urgent need for effective therapies and focuses on developing strategies for disease cure and prevention.
Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer. Cervical cancer is the commonest cause of cancer death in women under the age of 50 worldwide, the 8th most common cancer among women in Australia, and is the leading cause of cancer death in Aboriginal women. While a vaccine is available to prevent HPV-mediated disease, it would not impact upon death rates for at least 25 years. The systemic delivery of RNAi offers to best opportunity to solve this problem. The delivery devices w ....Engineered Polymer Nanoparticles: A Potent Weapon Against Cancer. Cervical cancer is the commonest cause of cancer death in women under the age of 50 worldwide, the 8th most common cancer among women in Australia, and is the leading cause of cancer death in Aboriginal women. While a vaccine is available to prevent HPV-mediated disease, it would not impact upon death rates for at least 25 years. The systemic delivery of RNAi offers to best opportunity to solve this problem. The delivery devices will be designed with precision and function to meet the delivery needs in vivo. These polymer structures will be suitable for use in drug and gene delivery providing Australian products with advanced features and capabilities, significantly improving product performance.Read moreRead less
Sterile inflammation as a determinant of adaptive immunity. When we injure ourselves, the site of injury becomes inflamed, which may help healing or cause trouble. This project aims to understand how the normal response to injury is controlled and why the process may sometimes go wrong.
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
Molecular grafting methods for design of peptide therapeutics. This project has the potential to lead to major economic benefits to Australia via royalty returns from novel drugs. Extra economic benefits derive from a reduction in the cost of treatment of diseases. The development of a new Australian developed peptide drug thus has the potential to lead to multimillion dollar savings to the Australian economy. Finally the project will provide training in state-of-the-art drug design that will e ....Molecular grafting methods for design of peptide therapeutics. This project has the potential to lead to major economic benefits to Australia via royalty returns from novel drugs. Extra economic benefits derive from a reduction in the cost of treatment of diseases. The development of a new Australian developed peptide drug thus has the potential to lead to multimillion dollar savings to the Australian economy. Finally the project will provide training in state-of-the-art drug design that will enhance Australia's pharmaceutical industry generally.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