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
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
Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid ....Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid separation, identification and quantification of isomeric lipids. These next generation technologies will be deployed in the hope of unmasking the molecular diversity within the lipidomes of two important mammalian cell types, thus providing fundamental new insights into the structure and function of lipids within living systems.Read moreRead less
New laser and mass spectrometry-based tools for comprehensive structural elucidation of lipids and their biomolecular interactions. Lipid-related disorders such as obesity, diabetes and heart disease are reaching epidemic proportions. We propose the development of specialised instrumentation to identify and quantify lipids (fats) in tissue and culture samples thus providing Australian scientists with unique capabilities to investigate the mechanisms of disease.
DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic l ....DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic level and how either of the two main pathways is selected. The project aims to define how the activity of a key control protein, Sae2 (Sporulation in the Absence of Spo Eleven), is regulated by posttranslational modifications, and how this activates homologous recombination. The project plans to first use Saccharomyces cerevisiae yeast as a model and then to extend research into the human system in an attempt to improve the efficiency of genome editing. Read moreRead less
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
Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding ....Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding the effect of editing on how endogenous RNA is perceived by the innate immune system.Read moreRead less
Development of a non-invasive diagnostic test of Embryo Viability. A successful outcome will:
. improve the cost effectiveness of assisted reproductive technologies resulting in reduced health care costs and allowing greater use of ART in animal production
. by greater cost-effectiveness, facilitate greater access to these advanced technologies in less well developed economies
. build the national capacity in development and validation of biotech diagnostics
. build collaborative relationsh ....Development of a non-invasive diagnostic test of Embryo Viability. A successful outcome will:
. improve the cost effectiveness of assisted reproductive technologies resulting in reduced health care costs and allowing greater use of ART in animal production
. by greater cost-effectiveness, facilitate greater access to these advanced technologies in less well developed economies
. build the national capacity in development and validation of biotech diagnostics
. build collaborative relationship between the CI, University of Sydney and a leading industry partner (Cook Australia)
. lead to significant new fundamental knowledge in embryology that will be of major International significance
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Special Research Initiatives - Grant ID: SR0354892
Funder
Australian Research Council
Funding Amount
$40,000.00
Summary
The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these ....The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these enzymes. However this initiative aims to network their efforts by value-adding to the current protease research through promoting national and international collaborations to improve our understanding of biology, and encourage exploitation of proteases/inhibitors/receptors for pharmaceutical and industrial applications.Read moreRead less