The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.Read moreRead less
Developing next-generation mass spectrometry imaging with isomer resolution. Mass spectrometry imaging (MSI) is a rapidly emerging technology for mapping molecular distributions within biological samples. This project will bring together market-leading MSI instrumentation from the industry partner Waters Corporation with unique technologies developed at QUT and UOW to develop an integrated MSI-platform capable of achieving high mass- and spatial-resolution, as well as discrimination of lipid iso ....Developing next-generation mass spectrometry imaging with isomer resolution. Mass spectrometry imaging (MSI) is a rapidly emerging technology for mapping molecular distributions within biological samples. This project will bring together market-leading MSI instrumentation from the industry partner Waters Corporation with unique technologies developed at QUT and UOW to develop an integrated MSI-platform capable of achieving high mass- and spatial-resolution, as well as discrimination of lipid isomers. Resolution of lipid isomers using this instrumentation will afford researchers a first glimpse of isomer-resolved images that will be used to visualise tissue-specific changes resulting from underlying chemical, physical or metabolic processes; changes that are currently invisible to contemporary imaging technologies.Read moreRead less
Pluses and minuses of lipid mass spectrometry. This project aims to investigate the structural diversity of lipids. Lipids are among the most structurally diverse of all the biomolecules and thus deciphering their many functions requires bio-analytical technologies capable of uniquely identifying and quantifying individual molecules in a milieu of many thousands of analogues. Mass spectrometry is the pre-eminent technique for contemporary lipid analysis but is challenged by the preference of cer ....Pluses and minuses of lipid mass spectrometry. This project aims to investigate the structural diversity of lipids. Lipids are among the most structurally diverse of all the biomolecules and thus deciphering their many functions requires bio-analytical technologies capable of uniquely identifying and quantifying individual molecules in a milieu of many thousands of analogues. Mass spectrometry is the pre-eminent technique for contemporary lipid analysis but is challenged by the preference of certain lipids to ionise with a polarity that affords sensitive detection but does not permit detailed structure elucidation. This project will develop advanced instrumentation capable of on-demand polarity switching of ionised lipids such that the detection and interrogation of molecular structure can take place in the optimal charge state.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101055
Funder
Australian Research Council
Funding Amount
$448,737.00
Summary
How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The bene ....How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The benefits of these outcomes include generation of knowledge on the impact of tissue stiffness on the signalling mechanisms that drive formation and maintenance of blood vessels. In the long term, this fundamental understanding could give rise to major developments in emerging industries such as organ bioengineering.Read moreRead less
From trash to treasure: engineering waste carbon utilisation in yeast. This project aims to engineer yeast to convert carbon dioxide- and methane-derived methanol into sustainable chemicals, foods, and pharmaceuticals. This project expects to generate new design principles for methanol metabolism by using the innovative approach of laboratory evolution along with state-of-the-art bio-engineering capabilities at Macquarie University and The University of Queensland. Expected outcomes of this proj ....From trash to treasure: engineering waste carbon utilisation in yeast. This project aims to engineer yeast to convert carbon dioxide- and methane-derived methanol into sustainable chemicals, foods, and pharmaceuticals. This project expects to generate new design principles for methanol metabolism by using the innovative approach of laboratory evolution along with state-of-the-art bio-engineering capabilities at Macquarie University and The University of Queensland. Expected outcomes of this project include new manufacturing processes for chemicals and foods, discovery of novel metabolism in yeast, and enhanced collaboration between Australia, Denmark, and the United States. This Project will provide benefits through sustainable bio-manufacturing, new economic activity, and reduced greenhouse gas emissions.Read moreRead less
Cellular Ageing: Is the Plasma Membrane the Control Hub? This project aims to determine whether the plasma membrane lipid composition is a major driver of cellular ageing. It expects to generate new knowledge in the molecular mechanism of cellular ageing, utilising our team’s deep expertise in lipid biology, bioinformatics, biophysics, extracellular vesicle biology and cellular ageing. Expected outcomes include the identification of novel cellular ageing markers and anti-ageing targets while als ....Cellular Ageing: Is the Plasma Membrane the Control Hub? This project aims to determine whether the plasma membrane lipid composition is a major driver of cellular ageing. It expects to generate new knowledge in the molecular mechanism of cellular ageing, utilising our team’s deep expertise in lipid biology, bioinformatics, biophysics, extracellular vesicle biology and cellular ageing. Expected outcomes include the identification of novel cellular ageing markers and anti-ageing targets while also cementing long-standing partnerships and fostering new interdisciplinary collaborations. This cellular ageing study will provide novel insights into the basic principles of cellular behaviour, e.g. growth, differentiation, communication and death, reinforcing Australia’s leadership in biological science.Read moreRead less
Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less