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
Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only pro ....Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only provide fundamental information on catalytic mechanisms, but will also provide opportunities to manipulate enzyme specificity. Further, site-directed mutagenesis of the enzymes will be used to generate glycosynthases, which will be evaluated for their ability to synthesise novel oligosaccharide and polysaccharide products, some of which might show immunomodulating activity.Read moreRead less
Toll Like Receptor signalling as a mediator of sex differences in pain, opioid and alcohol action. Brain immunology will be examined in this project to see if the signalling of a receptor called Toll Like Receptor 4 can explain sex differences in pain, and the action of pain killers and alcohol. These findings will have significant implications on the understanding of male and female brains, and will assist in the design of new drugs to treat brain and spinal cord diseases.
Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.
Organic Bioelectronics: Solving Key Barriers to Precision Neuromodulation. This project aims to combine the principles of molecular electronics and neurobiology to create organic conductors with enhanced biocompatibility that enable optical neuromodulation. This project expects to generate new knowledge regarding the properties of materials that promote connectivity with neurons and the ability of new microscopy tools to visualise this bio-interface. The expected outcome of this project includes ....Organic Bioelectronics: Solving Key Barriers to Precision Neuromodulation. This project aims to combine the principles of molecular electronics and neurobiology to create organic conductors with enhanced biocompatibility that enable optical neuromodulation. This project expects to generate new knowledge regarding the properties of materials that promote connectivity with neurons and the ability of new microscopy tools to visualise this bio-interface. The expected outcome of this project includes new high performing materials, measurement tools and fabrication approaches to overcome the key challenges to precision neuromodulation. A significant benefit of the new materials is their printability, providing the opportunity to establish a sovereign capability to manufacture low-cost bioelectronic systems in Australia.Read moreRead less
Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously ....Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously, whilst recording intestinal muscle electrical activity and the movements of the gut wall, the project expects to identify which enteric neurochemical classes of neurons generate specific motor patterns along the intestine.Read moreRead less
Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less
Nanoengineering of Biomaterial Surfaces to Tailor Innate Immune Responses. The overarching aim of this project is to provide a mechanistic understanding of how surface nanotopography affects inflammatory responses. Recently, we showed that surface nanotopography induced conformational changes in adsorbed proteins can activate or deactivate immune cells. These exciting findings are important because they show that it may be possible to engineer the nanotopography of a biomedical device surface in ....Nanoengineering of Biomaterial Surfaces to Tailor Innate Immune Responses. The overarching aim of this project is to provide a mechanistic understanding of how surface nanotopography affects inflammatory responses. Recently, we showed that surface nanotopography induced conformational changes in adsorbed proteins can activate or deactivate immune cells. These exciting findings are important because they show that it may be possible to engineer the nanotopography of a biomedical device surface in a manner which leads to a desired and predictable level of inflammation. The outcomes of the project will create new fundamental knowledge that in the future can instruct the development of the next generation of biomaterials capable of controlling and directing the body’s inflammatory responses.Read moreRead less
Interactions between cells and extracellular matrix in the epithelial-mesenchymal transition of the ovarian follicular stratified epithelium. The lining of many mammalian organs and cavities contain cells that can transform into different cells to bring about organ development or repair but if it goes horribly wrong the cells become metastatic cancers. This project examines the key features of this process especially the roles of matrix that develops around the cells in this process.
Engineered plant receptors as orthogonal neuronal switches. This project aims to develop synthetic biology methods to study brain function by utilising engineered plant receptors. This project will expand our ability to manipulate nerve cell function with high specificity and without side effects in freely behaving animals. Plant receptors will be developed into molecular tools in an iterative process that improves key properties using rational protein design. Expected outcomes include innovativ ....Engineered plant receptors as orthogonal neuronal switches. This project aims to develop synthetic biology methods to study brain function by utilising engineered plant receptors. This project will expand our ability to manipulate nerve cell function with high specificity and without side effects in freely behaving animals. Plant receptors will be developed into molecular tools in an iterative process that improves key properties using rational protein design. Expected outcomes include innovative and broadly-applicable neuroscience methods and an understanding of receptors involved in plant growth and defense. Benefits of this project include an enhanced capacity to generate knowledge, multidisciplinary training opportunities and patentable synthetic biology technologies.Read moreRead less