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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
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
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
Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost a ....Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost and time. This project should overcome a major barrier to studying gene function with unprecedented detail, thereby opening new avenues for future research into biological processes. Thus, the outcomes from this project should impact on the entire field of biomedical research, and advance Australia's biotech industry.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
A Network Approach To Mapping And Modifying Brain Changes In Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$2,163,245.00
Summary
Psychosis fundamentally alters a person’s relationship with reality. Brain scans can map which parts of the brain are affected by psychosis, but they cannot reveal the actual disease processes that cause these changes. I will address this gap by integrating brain imaging with genetics and mathematical modelling to identify the brain circuits and molecules that impact risk for psychosis, and to develop targeted therapies that modify risk-related brain dysfunction.
Detection and viability of waterborne pathogens using a gut-on-chip. This project aims to resolve a significant problem for water utilities. Microbial pathogens Cryptosporidium, norovirus and adenovirus are the main public health concern for drinking water in developed nations. Water monitoring is limited by the lack of fast, reliable detection methods and viability assays for these pathogens. This project will use a novel gut-on-a-chip to develop for the first time rapid infectivity assays for ....Detection and viability of waterborne pathogens using a gut-on-chip. This project aims to resolve a significant problem for water utilities. Microbial pathogens Cryptosporidium, norovirus and adenovirus are the main public health concern for drinking water in developed nations. Water monitoring is limited by the lack of fast, reliable detection methods and viability assays for these pathogens. This project will use a novel gut-on-a-chip to develop for the first time rapid infectivity assays for Cryptosporidium, norovirus and adenovirus. Significant benefits include improved diagnostics and water disinfection assays, improved water treatment and reduced costs with global impact.Read moreRead less
Defining the Microbial-scale Processes Governing Ocean Health . This project aims to resolve the foundations of healthy ocean function by employing innovative approaches to uncover the links between marine chemistry and microbiology. While the importance of microbes in governing ocean health is unquestionable, they are often studied over inappropriately large-scales, leading to inaccurate interpretation of the oceanic processes that ultimately influence fishery production and climate control. W ....Defining the Microbial-scale Processes Governing Ocean Health . This project aims to resolve the foundations of healthy ocean function by employing innovative approaches to uncover the links between marine chemistry and microbiology. While the importance of microbes in governing ocean health is unquestionable, they are often studied over inappropriately large-scales, leading to inaccurate interpretation of the oceanic processes that ultimately influence fishery production and climate control. We will develop new oceanographic tools and analytical techniques to provide a unique "microbes-eye-view" of the sea. The project's outcomes are anticipated to deliver transformative new knowledge on the controls of ocean productivity and sustainability, helping to safeguard Australia’s valuable marine estate.Read moreRead less