Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.Read moreRead less
Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultim ....Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultimately inform our capacity to better deploy personalised medicines.Read moreRead less
Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host ....Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host parasite interactions which may in turn suggest novel approaches or pathways to persue. This may eventually lead to the development of novel therapeutics.
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Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Discovery Early Career Researcher Award - Grant ID: DE130101191
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Formation of the osteocyte network in bone matrix. The formation of new bone, which occurs throughout life for bone renewal and acutely after fractures, entraps a network of cells that can detect micro-damage and direct repair mechanisms. Mathematical and computational methods will be used to understand how this network can lead to a self-detecting and self-repairing biomaterial.
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100179
Funder
Australian Research Council
Funding Amount
$3,189,000.00
Summary
Automated high resolution and high contrast cryo -TEM for three-dimensional structural biology. This project aims to establish a facility in automated, single-particle cryo-TEM and cryo-TEM tomography (Titan Krios) that will enable atomic and molecular structure research and three-dimensional subcellular and cellular imaging. The project will span all multiscale cryo-TEM modalities from the visualisation of cells, membranes and macromolecular complexes, through to near-atomic-resolution protein ....Automated high resolution and high contrast cryo -TEM for three-dimensional structural biology. This project aims to establish a facility in automated, single-particle cryo-TEM and cryo-TEM tomography (Titan Krios) that will enable atomic and molecular structure research and three-dimensional subcellular and cellular imaging. The project will span all multiscale cryo-TEM modalities from the visualisation of cells, membranes and macromolecular complexes, through to near-atomic-resolution protein structure determination. Cryo-single particle analysis and tomography are recognised as revolutionary technologies in molecular structural biology and powerful enablers of future ground-breaking discovery. The project will deliver significant competitive advantage for Australia in leading-edge structure-based research, drug discovery, new opportunities for applied research and development, and showcasing science to the public.Read moreRead less
Identifying how cortical bone microstructure deteriorates with age. This project aims to define the disruptions responsible for the gradual weakening of the skeleton in ageing by integrating a range of high-resolution imaging, biomechanical, and computational methods. The expected significance of this project includes a full definition and comparison of the cellular and subcellular organisation of bone from young and elderly individuals. Expected outcomes of this international project include th ....Identifying how cortical bone microstructure deteriorates with age. This project aims to define the disruptions responsible for the gradual weakening of the skeleton in ageing by integrating a range of high-resolution imaging, biomechanical, and computational methods. The expected significance of this project includes a full definition and comparison of the cellular and subcellular organisation of bone from young and elderly individuals. Expected outcomes of this international project include the establishment of a new multidisciplinary research team, and the development of a new data-driven theoretical framework for understanding the nature and the causes of age-related bone fragility. Potential long-term benefits include new ways to treat age-related osteoporosis.Read moreRead less