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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Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less
Understanding the biogenesis of exosomes. This project aims to understand how exosomes are made in human cells. Exosomes are small packages that are released by cells, which mediate communication between cells. Currently, very little is known about how exosomes are made within a cell. This project expects to identify key proteins that are involved in the production of exosomes and to understand exosomes synthesis, thereby expanding our knowledge on how cells regulate communication signals. Disse ....Understanding the biogenesis of exosomes. This project aims to understand how exosomes are made in human cells. Exosomes are small packages that are released by cells, which mediate communication between cells. Currently, very little is known about how exosomes are made within a cell. This project expects to identify key proteins that are involved in the production of exosomes and to understand exosomes synthesis, thereby expanding our knowledge on how cells regulate communication signals. Dissecting how exosomes are produced at the fundamental level will provide significant benefits such as a deeper understanding of how cells maintain normal cellular functions.Read moreRead less
Characterising O-linked glycosylation across Burkholderia. Protein glycosylation, the chemical addition of sugars to proteins, enables the augmentation of protein properties. Across the Burkholderia genus we have shown O-linked glycosylation is both conserved as well as essential for bacterial fitness. Yet, we have little understanding of how glycosylation modulates the proteome of this genus. This project aims to characterise the glycoproteomes of Burkholderia species and track the impact of gl ....Characterising O-linked glycosylation across Burkholderia. Protein glycosylation, the chemical addition of sugars to proteins, enables the augmentation of protein properties. Across the Burkholderia genus we have shown O-linked glycosylation is both conserved as well as essential for bacterial fitness. Yet, we have little understanding of how glycosylation modulates the proteome of this genus. This project aims to characterise the glycoproteomes of Burkholderia species and track the impact of glycosylation on both the proteome and protein stability. By understanding how glycosylation shapes the proteome we will gain a greater understanding of the role of bacterial glycosylation in Burkholderia physiology as well as how we may better utilise microbial glycosylation for glycoprotein production.Read moreRead less
An integrated nano-bioengineered chip for enhanced molecular evolution. This project aims to develop a novel molecular evolution platform technology for the rapid selection of high value target binding molecules from diverse molecular libraries using an electrically activated nanofluidic chip coated with target. Significant outcomes from the project is the controlled selection of target binding molecules that is not possible with current methods and improved understanding of nanoforce driven mol ....An integrated nano-bioengineered chip for enhanced molecular evolution. This project aims to develop a novel molecular evolution platform technology for the rapid selection of high value target binding molecules from diverse molecular libraries using an electrically activated nanofluidic chip coated with target. Significant outcomes from the project is the controlled selection of target binding molecules that is not possible with current methods and improved understanding of nanoforce driven molecular collisions on nano-bioengineered surfaces. This provides significant benefits, creating new knowledge in nanomaterials and advanced manufacturing of nanofabricated devices, creating commercial interest and positioning Australia at the forefront of molecular discovery technology, a highly valuable global market.
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Discovery Early Career Researcher Award - Grant ID: DE200100611
Funder
Australian Research Council
Funding Amount
$427,116.00
Summary
How do extracellular vesicles fuse with cells to deliver messages? Aims: This project aims to investigate how tiny packages released by all cells in the human body, called extracellular vesicles, deliver messages into neighbouring cells facilitating cell-to-cell communication.
Significance: This project expects to generate key knowledge in the area of cell-to-cell communication by using innovative molecular biology approaches and cutting-edge microscopy and biophysical techniques.
Expected outco ....How do extracellular vesicles fuse with cells to deliver messages? Aims: This project aims to investigate how tiny packages released by all cells in the human body, called extracellular vesicles, deliver messages into neighbouring cells facilitating cell-to-cell communication.
Significance: This project expects to generate key knowledge in the area of cell-to-cell communication by using innovative molecular biology approaches and cutting-edge microscopy and biophysical techniques.
Expected outcomes: Expected outcomes include high resolution details of which molecules are packaged onto extracellular vesicles and how they are delivered into recipient cells.
Benefits: This project should contribute significantly to understanding extracellular vesicle function and guide their eventual use as therapeutics.Read moreRead less