Discovery Early Career Researcher Award - Grant ID: DE220100964
Funder
Australian Research Council
Funding Amount
$443,869.00
Summary
Statistical approaches for spatial genomics at single cell resolution. Cells cooperate to form complex, dynamic and varied tissue structures. This project aims to develop statistical and computational approaches to analyse spatial genomics data, a novel technology that retains vital spatial information at single cell resolution while detecting RNA molecules for hundreds of genes. Observing the molecular activity of cells in their spatial context is critical for tackling key biological questions, ....Statistical approaches for spatial genomics at single cell resolution. Cells cooperate to form complex, dynamic and varied tissue structures. This project aims to develop statistical and computational approaches to analyse spatial genomics data, a novel technology that retains vital spatial information at single cell resolution while detecting RNA molecules for hundreds of genes. Observing the molecular activity of cells in their spatial context is critical for tackling key biological questions, such as how tumour cells behave during malignancy or how stem cells determine their fate. Expected outcomes also include techniques to fully harmonise spatial and non-spatial genomics datasets, and methods toward understanding the complex relationships among cells in their environment, revealing novel cell biology.Read moreRead less
Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematic ....Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematical model of the regulation of cell-shape and volume. The project will provide an understanding of mechanisms operating when cells and tissues are succumbing to trauma and invasion, and how to control these processes on a molecular level.Read moreRead less
Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods ....Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods. The expected outcome is to deliver new methodology for a comprehensive understanding of the correlation between quality control machinery, stress responses and cell functions. This should provide significant benefits, including contributing to fundamental knowledge on the molecular causes of neurodegenerative diseases.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100206
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Intelligently linking nanoscience to neuroscience with glycan biology. This project aims to provide a comprehensive description of the unique cell-surface glycan expression on inflamed neurons, astrocytes, microglia and oligodendrocytes. This project will use glycan profiling data to engineer luminescent nanoparticles with superior neuroimaging qualities for cell type-specific in vivo targeting and drug delivery in the central nervous system. The project outcomes are expected to improve our fund ....Intelligently linking nanoscience to neuroscience with glycan biology. This project aims to provide a comprehensive description of the unique cell-surface glycan expression on inflamed neurons, astrocytes, microglia and oligodendrocytes. This project will use glycan profiling data to engineer luminescent nanoparticles with superior neuroimaging qualities for cell type-specific in vivo targeting and drug delivery in the central nervous system. The project outcomes are expected to improve our fundamental understanding of neurobiological cell-surfaces.Read moreRead less
A scalable, synthetic retina: signal processing in droplet systems with DNA. This project aims to design DNA-based nanotechnology for processing optical signals in synthetic biological systems. The intended outcome of this project is to develop a system for signal transduction in artificial bilayers using new DNA nanostructures. The anticipated goal of the project is to deliver: 1) light-based control of membrane protein insertion into artificial bilayers; 2) novel DNA-based pores that can trans ....A scalable, synthetic retina: signal processing in droplet systems with DNA. This project aims to design DNA-based nanotechnology for processing optical signals in synthetic biological systems. The intended outcome of this project is to develop a system for signal transduction in artificial bilayers using new DNA nanostructures. The anticipated goal of the project is to deliver: 1) light-based control of membrane protein insertion into artificial bilayers; 2) novel DNA-based pores that can transduce signals across membranes; 3) signal processing using multi-compartment biological components composed. Together, this technology allows us to use light and external signals to control biochemical pathways in synthetic systems.Read moreRead less
Resurrecting Ancient Proteins to Unlock New Catalytic Activity. This project aims to study the proteins that nature uses to make penicillin and related antibiotics, and their prehistoric ancestors. By doing so, the project expects to deepen understanding of these important processes, open up ways to make new antibiotics, and generate new knowledge about protein evolution. Intended outcomes include new biocatalysts based on the ancient ones, new antibiotic compounds active against resistant bacte ....Resurrecting Ancient Proteins to Unlock New Catalytic Activity. This project aims to study the proteins that nature uses to make penicillin and related antibiotics, and their prehistoric ancestors. By doing so, the project expects to deepen understanding of these important processes, open up ways to make new antibiotics, and generate new knowledge about protein evolution. Intended outcomes include new biocatalysts based on the ancient ones, new antibiotic compounds active against resistant bacteria, and a richer understanding of how these proteins have evolved over the last 4 billion years. This promises significant benefits in the form of new ways to address the challenge posed by antimicrobial resistance to antibiotics, which is a serious threat to the continued effectiveness of current antibiotics.Read moreRead less
Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dime ....Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dimension reduction multivariate method developments for data integration. By combining in silico and in vivo approaches, the project is anticipated to benefit scientists willing to work in cutting-edge single-cell research by providing useful protocols and tools to generate novel insights in cell biology. Read moreRead less
Elucidating the determinants of cation import across the kingdoms of life. The metal ion manganese is essential to all forms of life. This project aims to investigate how this poorly abundant cation is selectively acquired from the chemical complexity of the environment for import into cells by using state-of-the-art biochemical and microbiological techniques. This project expects to define the fundamental basis for how bacterial, archaeal and eukaryotic plastid cation-selective importers can di ....Elucidating the determinants of cation import across the kingdoms of life. The metal ion manganese is essential to all forms of life. This project aims to investigate how this poorly abundant cation is selectively acquired from the chemical complexity of the environment for import into cells by using state-of-the-art biochemical and microbiological techniques. This project expects to define the fundamental basis for how bacterial, archaeal and eukaryotic plastid cation-selective importers can discriminate manganese from chemical similar cations to achieve selective uptake. The expected outcomes of this work will be an understanding of the fundamental basis for selective metal import in biological systems. This should provide benefits for industry through synthetic biological applications of this knowledge. Read moreRead less
Unravelling a canonical mitochondrial stress response pathway. Stress has a major impact on all life forms and is considered one of the key determinants of healthy ageing. This project aims to unravel a highly novel pathway through which many different forms of stress converge to induce a conserved stress response in mammalian cells. Major outcomes include rewriting the textbook on how stress is sensed by cells and how cells respond to this stress and will provide novel approaches and technologi ....Unravelling a canonical mitochondrial stress response pathway. Stress has a major impact on all life forms and is considered one of the key determinants of healthy ageing. This project aims to unravel a highly novel pathway through which many different forms of stress converge to induce a conserved stress response in mammalian cells. Major outcomes include rewriting the textbook on how stress is sensed by cells and how cells respond to this stress and will provide novel approaches and technologies for studying stress in a broad range of organisms and systems. This project will benefit all efforts to understand stress and aid efforts by others to ameliorate stress-mediated health defects across the animal kingdomRead moreRead less
Uncovering New Mechanisms of Metabolite-Sensing and Signaling. This project aims to understand how cells sense changes in metabolic activity, to ensure energy demands are matched with nutrient supply. Our proposal will fill critical gaps in our understanding of the molecular mechanisms underlying metabolic sensing. This will generate new knowledge with far reaching potential for Australian industries that rely on the propagation and utilization of living organisms, including agriculture, biotech ....Uncovering New Mechanisms of Metabolite-Sensing and Signaling. This project aims to understand how cells sense changes in metabolic activity, to ensure energy demands are matched with nutrient supply. Our proposal will fill critical gaps in our understanding of the molecular mechanisms underlying metabolic sensing. This will generate new knowledge with far reaching potential for Australian industries that rely on the propagation and utilization of living organisms, including agriculture, biotechnology and brewing, as well as knowledge relevant to sporting performance and the metabolic dimensions of ageing. This project will support advanced training of early career researchers and PhD students, which will expand Australian research capabilities and contribute to a producing a highly skilled workforce.Read moreRead less