Discovery Early Career Researcher Award - Grant ID: DE200101511
Funder
Australian Research Council
Funding Amount
$424,816.00
Summary
Structural insights into activation, dynamics and bias of GPCRs. The project aims to investigate the mechanisms underlying activation, biased agonism and G protein selectivity of G protein-coupled receptors (GPCRs) by utilising the adenosine A1 receptor as a model system. This project expects to generate knowledge in the area of GPCR biology using an interdisciplinary approach including structural biology, pharmacology, biochemistry and protein engineering. The expected outcomes include (i) unde ....Structural insights into activation, dynamics and bias of GPCRs. The project aims to investigate the mechanisms underlying activation, biased agonism and G protein selectivity of G protein-coupled receptors (GPCRs) by utilising the adenosine A1 receptor as a model system. This project expects to generate knowledge in the area of GPCR biology using an interdisciplinary approach including structural biology, pharmacology, biochemistry and protein engineering. The expected outcomes include (i) understanding the structural mechanisms underlying GPCR activation, (ii) biased agonism and (iii) G protein selectivity. This should provide significant benefits, such as advancement of fundamental knowledge in GPCR biology and pharmacology that could also one day lead to therapeutic development.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100029
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
High Resolution PET-CT for Small Animal Molecular and Anatomical Imaging. This project will integrate a next generation small animal PET-CT instrument into the Sydney Imaging multi-modality imaging ecosystem. PET-CT enables the investigation of molecular function and anatomical structure in complex living organisms. This platform will enable research as diverse as the development and in-vivo characterisation of new chemical probes and nanoparticles that bind to specific protein targets in the bo ....High Resolution PET-CT for Small Animal Molecular and Anatomical Imaging. This project will integrate a next generation small animal PET-CT instrument into the Sydney Imaging multi-modality imaging ecosystem. PET-CT enables the investigation of molecular function and anatomical structure in complex living organisms. This platform will enable research as diverse as the development and in-vivo characterisation of new chemical probes and nanoparticles that bind to specific protein targets in the body, investigating mechanisms of brain plasticity in predictive learning, understanding the molecular pathways involved in neurodegeneration and cancer, developing novel methods for multi-modal image analysis, and developing and validating new radiation detectors for the next generation of imaging technology.Read moreRead less
Novel tractography-guided MRI methods for studying healthy brain ageing. Advances in imaging, and particularly Magnetic Resonance Imaging, have opened a new era in the study of the brain enabling a myriad of neuroscience discoveries. This project aims to develop new analysis methods to study and understand the variability in the human brain during ageing, exploiting the wealth of information contained in the so-called tractogram, a mapping of the brain’s wiring. This project expects to develop i ....Novel tractography-guided MRI methods for studying healthy brain ageing. Advances in imaging, and particularly Magnetic Resonance Imaging, have opened a new era in the study of the brain enabling a myriad of neuroscience discoveries. This project aims to develop new analysis methods to study and understand the variability in the human brain during ageing, exploiting the wealth of information contained in the so-called tractogram, a mapping of the brain’s wiring. This project expects to develop innovative imaging biomarkers to characterise the brain changes in the course of healthy brain ageing. Expected outcomes include novel imaging tools for neuroscience, which should allow us to map trajectories of normative healthy brain ageing and use them to identify lifestyle factors that impact these trajectories.Read moreRead less
Neurovascular pericytes in development and brain regeneration. The brain is responsible for a quarter of the body’s metabolism and is thus perfused by an extensive network of blood vessels. Pericytes surround these vessels and interact with neurons, glia, immune cells and neural stem cells of the neurovascular unit. Pericytes influence brain development, function and regeneration but remain enigmatic. This project investigates molecular control of pericyte development, functional coupling of per ....Neurovascular pericytes in development and brain regeneration. The brain is responsible for a quarter of the body’s metabolism and is thus perfused by an extensive network of blood vessels. Pericytes surround these vessels and interact with neurons, glia, immune cells and neural stem cells of the neurovascular unit. Pericytes influence brain development, function and regeneration but remain enigmatic. This project investigates molecular control of pericyte development, functional coupling of pericytes with adjacent cells and pericyte function in tissue regeneration. We aim to produce new fundamental knowledge in brain development, structure, function and evolution. New knowledge generated here may lead to future approaches in stem cell biology, tissue engineering, regeneration and ageing of the brain. Read moreRead less
Supercritical-microfluidics technology for targeted delivery to the colon. This research will develop nanosystems to target delivery of drugs to the colon. Our nanosystems will permit the combination of clinically used chemotherapy drugs within a single dosage form. This will improve the efficiency of delivery to the colon while reducing unwanted side-effects. A novel supercritical microfluidics system will be developed to produce therapeutic nano-carriers in a continuous mode with lower labour ....Supercritical-microfluidics technology for targeted delivery to the colon. This research will develop nanosystems to target delivery of drugs to the colon. Our nanosystems will permit the combination of clinically used chemotherapy drugs within a single dosage form. This will improve the efficiency of delivery to the colon while reducing unwanted side-effects. A novel supercritical microfluidics system will be developed to produce therapeutic nano-carriers in a continuous mode with lower labour requirement, higher production rate and better quality control than conventional production methods. The new process will combine benefits from both supercritical fluid technology (green process) and microfluidics (high mass & heat transfer).Read moreRead less
The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along ....The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along with a novel methodology for validating mathematical models against experimental data. These innovations offer a completely fresh approach to identifying and modulating the adaptive capacities of living cells, which may contribute to overcoming the problem of drug resistance in future therapeutic development.
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Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected out ....Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected outcomes:
We will identify a new mechanism that governs tissue development, and introduce new imaging and genetic technologies to the Australian research community.
Benefit:
We expect potential economic and commercial interest in development of new gene analysis tools and biotechnological tissue manipulation applications.Read moreRead less
Decoding miRNA regulated genetic circuits. This project will aim to develop a much better understanding of how the process of making proteins from genes is regulated, and will develop scientific software capable of predicting how a cell will respond to changes in this regulation. The results will have widespread use, including assistance in deciding the best treatments for genetic diseases.
Microbe-produced repellents and their roles in marine pathogen behaviours. Economic losses caused by disease outbreaks in marine fisheries and aquaculture exceed US$6 billion per year globally. Decades of research in human and plant pathogens have revealed that the ability of pathogens to infect their host is governed by behaviours; however our understanding of the chemical cues affecting the behaviour of marine pathogens is very poor. This research program aims to combine new approaches in micr ....Microbe-produced repellents and their roles in marine pathogen behaviours. Economic losses caused by disease outbreaks in marine fisheries and aquaculture exceed US$6 billion per year globally. Decades of research in human and plant pathogens have revealed that the ability of pathogens to infect their host is governed by behaviours; however our understanding of the chemical cues affecting the behaviour of marine pathogens is very poor. This research program aims to combine new approaches in microfluidics and chemical imaging to identify the cues that govern the behaviour of marine pathogens. Expected outcomes include an improved capacity to predict, monitor and manage marine diseases, as well as novel strategies to prevent disease outbreaks, helping to protect Australia’s valuable marine estate.Read moreRead less
Understanding how an old heart gets stiff. Aging is accompanied by a stiffening of the heart and reduced function, which is accelerated by cardiovascular disease and leads to heart failure. How the heart stiffens is poorly understood. A new mechanism is proposed here, involving structural membrane proteins (termed caveolae and cavins) and a signalling molecule (nitric oxide). The current research aims to unravel the interplay between cardiac cells and these proteins/signals to cause stiffness an ....Understanding how an old heart gets stiff. Aging is accompanied by a stiffening of the heart and reduced function, which is accelerated by cardiovascular disease and leads to heart failure. How the heart stiffens is poorly understood. A new mechanism is proposed here, involving structural membrane proteins (termed caveolae and cavins) and a signalling molecule (nitric oxide). The current research aims to unravel the interplay between cardiac cells and these proteins/signals to cause stiffness and to determine whether this process governs normal aging of the heart. This work will advance understanding of how heart function is determined and reveal how the human heart changes with normal aging. Read moreRead less