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
Androgen receptor: A master regulator of lipid metabolism. This project aims to understand how male sex hormones, or androgens, affect the amount and metabolism of fats in normal body tissues. By integrating our multi-disciplinary expertise in androgen action, molecular biology, metabolism and bioinformatics with novel techniques and instrumentation, this collaboration expects to generate the first detailed picture of how fat metabolism is controlled by androgens in humans, and how closely this ....Androgen receptor: A master regulator of lipid metabolism. This project aims to understand how male sex hormones, or androgens, affect the amount and metabolism of fats in normal body tissues. By integrating our multi-disciplinary expertise in androgen action, molecular biology, metabolism and bioinformatics with novel techniques and instrumentation, this collaboration expects to generate the first detailed picture of how fat metabolism is controlled by androgens in humans, and how closely this relates to mice. Expected outcomes and benefits will be a new understanding of which aspects of fat metabolism are most influenced by androgens, and an ability to anticipate potential metabolic impacts of natural or pharmacological fluctuations in androgen levels in humans, laboratory animals and livestock.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
The colour of cellular aging: a deep probe of cellular processes. Understanding why we age and whether aging is preventable are profound research challenges, which must be first tackled at a cellular level. Building on our advances in non-invasive colour monitoring of cell function, this project aims to uncover intimate links between cellular processes and aging in cells that must survive for many decades such as oocytes and neurons. We will explore the tantalising possibility to rejuvenate such ....The colour of cellular aging: a deep probe of cellular processes. Understanding why we age and whether aging is preventable are profound research challenges, which must be first tackled at a cellular level. Building on our advances in non-invasive colour monitoring of cell function, this project aims to uncover intimate links between cellular processes and aging in cells that must survive for many decades such as oocytes and neurons. We will explore the tantalising possibility to rejuvenate such aged cells by interfering with molecular master switches of aging. A unique machine learning approach will be applied for finding the most effective interventions. The results will have broad impact beyond the science of aging, in the areas of female fertility, neurodegeneration and immunity.
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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
The role of phospholipids in the biogenesis of lipid droplets. The general aim is to elucidate the fundamental molecular mechanisms that govern the biogenesis/formation of the lipid droplets. Lipid droplets store sterol esters and/or triacylglycerols, two major storage lipids that play key roles in cellular and whole body lipid metabolism. Lipid droplets are also the core components of plant oil and biodiesel. Little is known about how lipid droplets are generated. The proposed work will examine ....The role of phospholipids in the biogenesis of lipid droplets. The general aim is to elucidate the fundamental molecular mechanisms that govern the biogenesis/formation of the lipid droplets. Lipid droplets store sterol esters and/or triacylglycerols, two major storage lipids that play key roles in cellular and whole body lipid metabolism. Lipid droplets are also the core components of plant oil and biodiesel. Little is known about how lipid droplets are generated. The proposed work will examine the synthesis of certain lipid intermediates such as phosphatidic acid, and their impact on the biogenesis of lipid droplets from the endoplasmic reticulum. Such fundamental new knowledge on how cells store neutral lipids will provide new strategies for enhancing plant oil and biodiesel production. Read moreRead less
The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artifi ....The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artificial regulation of the ribosome may also emerge, relevant to synthetic biology and the engineering of industrial yeasts. The project should provide significant new findings for the research community, generate research citations and contribute to a highly skilled workforce by the training of staff and students.Read moreRead less
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.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