The role of HP1 alpha dimerisation in maintaining chromatin structure. Heterochromatin protein 1 alpha (HP1a) is an architectural protein that decorates three-dimensional genome organisation and through self-association into HP1a dimers regulates global gene expression. While there is extensive biochemical evidence on how HP1a molecules bind DNA, dimerise and bridge nucleosomes close together, we still do not know how HP1a regulates higher order chromatin structure in the context of a living cel ....The role of HP1 alpha dimerisation in maintaining chromatin structure. Heterochromatin protein 1 alpha (HP1a) is an architectural protein that decorates three-dimensional genome organisation and through self-association into HP1a dimers regulates global gene expression. While there is extensive biochemical evidence on how HP1a molecules bind DNA, dimerise and bridge nucleosomes close together, we still do not know how HP1a regulates higher order chromatin structure in the context of a living cell. Thus, by use of cutting-edge fluorescence microscopy methods, the overall aim of this research project is to determine the biophysical mechanism by which the HP1a monomer to dimer transition spatially and temporally modulates live cell chromatin network organisation to ensure faithful transmission of the genome.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100046
Funder
Australian Research Council
Funding Amount
$289,381.00
Summary
A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolut ....A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolution. The benefit of this technology is that it will enable scientists in Australia to image, for the first time, the biophysical mechanism by which a protein navigates intracellular architecture to regulate a complex biological function at the single molecule level.Read 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
Systems-level characterization of scaffold protein signalling networks. The PEAK family of cell signalling scaffolds regulate cellular responses critical for normal development and physiology. This project will adopt a ‘holistic’ approach to characterizing their mechanism and function, integrating experimental and mathematical approaches and developing predictive computational models. It aims to generate fundamental new knowledge in cell, computational and synthetic biology with broad relevance ....Systems-level characterization of scaffold protein signalling networks. The PEAK family of cell signalling scaffolds regulate cellular responses critical for normal development and physiology. This project will adopt a ‘holistic’ approach to characterizing their mechanism and function, integrating experimental and mathematical approaches and developing predictive computational models. It aims to generate fundamental new knowledge in cell, computational and synthetic biology with broad relevance that will foster establishment of new international linkages. This research will also identify strategies for engineering novel scaffolds that re-program cellular behaviour towards specific, applied outcomes, with potential benefit for the fields of synthetic biology, bioengineering and biotechnology.Read moreRead less
Defining the molecular switches that govern discrete cellular fates. This project aims to elucidate how mammalian cells exploit the same molecular machinery to perform completely distinct jobs. While the repurposing of proteins by cells seems widespread, the mechanisms by which this occurs remains largely undefined. The project expects to generate new knowledge in the areas of cell signalling and systems biology, with important implications for many multi-functional proteins. It will utilise a h ....Defining the molecular switches that govern discrete cellular fates. This project aims to elucidate how mammalian cells exploit the same molecular machinery to perform completely distinct jobs. While the repurposing of proteins by cells seems widespread, the mechanisms by which this occurs remains largely undefined. The project expects to generate new knowledge in the areas of cell signalling and systems biology, with important implications for many multi-functional proteins. It will utilise a highly innovative and interdisciplinary approach that tightly integrates mathematical modelling and biological experiments. The expected outcomes will aid strategies for reprogramming cells towards a desired phenotype, which will bring significant benefits to the fields of synthetic biology and bioengineering.Read moreRead less
Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing inter ....Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing international collaborations, enhancing Australia’s competitiveness and reputation in an important area of research, and provide training of HDR students in skills across a range of areas. In the long-term the research findings may translate into improved agriculture, food production and human health outcomes.Read moreRead less
The role of phosphoinositides in endosomal maturation dynamics. This project aims to investigate the regulation of an intracellular compartment within a cell called endosomes, which plays critical roles in cellular homeostasis, signalling and pathogen entry. New knowledge is expected to be generated in understanding endosome maturation and the signalling events that drive this process using a unique, multidisciplinary approach combining state of the art imaging techniques and high throughput pro ....The role of phosphoinositides in endosomal maturation dynamics. This project aims to investigate the regulation of an intracellular compartment within a cell called endosomes, which plays critical roles in cellular homeostasis, signalling and pathogen entry. New knowledge is expected to be generated in understanding endosome maturation and the signalling events that drive this process using a unique, multidisciplinary approach combining state of the art imaging techniques and high throughput protein analysis. The anticipated outcomes will be to define the molecular steps that govern the membrane-bound machinery on endosomes that directs endosomal maturation. This should provide significant benefits in delineating a process that is linked to almost all aspects of cell life.Read moreRead less
Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that h ....Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that has previously been overlooked. This project aims to understand how this pathway works and how it contributes to the normal workings of cells. This fundamental science has future consequences for the design of vaccines and for the design of therapeutics to treat diseases that show defective interferon signalling.Read moreRead less
Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is acti ....Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is activated responding to different ligands. The anticipated outcome including an enhanced capacity for understanding the fundamental biology, a stronger national and international collaborations. This will provide significant benefits including expanded basic knowledge and improvements in drug development efficiency. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100259
Funder
Australian Research Council
Funding Amount
$467,964.00
Summary
Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. T ....Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. This project will provide fundamental new knowledge in understanding how modifying muscle attributes influence successful ageing. This knowledge will improve resilience, productivity, and wellbeing of all Australians, with implications for reducing societal and economic burden.Read moreRead less