Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less
Characterizing the regulators of mitochondrial biogenesis in Arabidopsis thaliana. The overall aim of this project is to identify and characterise the underlying regulatory factors that control mitochondrial mass and number in plants. The project will exploit a regulatory mechanism that links the mitochondrial import machinery and the respiratory chain. Utilising both forward and reverse genetic approaches, the abundances of protein import translocases will be altered and the changes to mitochon ....Characterizing the regulators of mitochondrial biogenesis in Arabidopsis thaliana. The overall aim of this project is to identify and characterise the underlying regulatory factors that control mitochondrial mass and number in plants. The project will exploit a regulatory mechanism that links the mitochondrial import machinery and the respiratory chain. Utilising both forward and reverse genetic approaches, the abundances of protein import translocases will be altered and the changes to mitochondrial biogenesis will be investigated. This will identify regulatory factors, which can be manipulated and used to alter mitochondrial number and activity.Read moreRead less
The targeting of macromolecules to alter mitochondrial function. Mitochondria are essential organelles involved in energy production and specific metabolic pathways in plant cells that require the import of cytosolic transfer RNA (tRNA) to function. To date our knowledge on the mechanisms of tRNA import is limited. This project seeks to characterise putative receptors and mechanisms with the purpose of exploiting these insights to allow for the manipulation and modification of macromolecule targ ....The targeting of macromolecules to alter mitochondrial function. Mitochondria are essential organelles involved in energy production and specific metabolic pathways in plant cells that require the import of cytosolic transfer RNA (tRNA) to function. To date our knowledge on the mechanisms of tRNA import is limited. This project seeks to characterise putative receptors and mechanisms with the purpose of exploiting these insights to allow for the manipulation and modification of macromolecule targeting to mitochondria. The ability to modify or alter mitochondrial biogenesis and activity may allow for new approaches to be undertaken to increase plant growth, productivity and resistance to stress.Read moreRead less
Characterising the transport and delivery of oligonucleotides . Short RNA and DNA molecules represent a class of macromolecules that have great potential, but to facilitate their trafficking across cellular and membrane barriers into specific sites of action is challenging. This project aims to develop and apply novel imaging approaches to track them in cells and tissues. Expected outcomes include better understanding of the trafficking across cellular and membrane barriers, and improved imaging ....Characterising the transport and delivery of oligonucleotides . Short RNA and DNA molecules represent a class of macromolecules that have great potential, but to facilitate their trafficking across cellular and membrane barriers into specific sites of action is challenging. This project aims to develop and apply novel imaging approaches to track them in cells and tissues. Expected outcomes include better understanding of the trafficking across cellular and membrane barriers, and improved imaging tools that could be used to further study the molecular mechanisms of accumulation, metabolism and trafficking of these molecules. This project should provide new strategies to target these molecules to specific cells and tissues, which have significant social and economic benefits to the Australian community.Read moreRead less
Deciphering organelle transport mechanisms in plants. Plant growth, productivity and seed yield all depend on organelle function which requires metabolites and proteins
to be transported across membranes. This mechanism of transport is carried out by specific transporters that have
the ability to transport macromolecules, and regulate organelle function. We have identified new transporters that
are involved in amino acid and protein transport in the mitochondria, chloroplast and peroxisomes. We ....Deciphering organelle transport mechanisms in plants. Plant growth, productivity and seed yield all depend on organelle function which requires metabolites and proteins
to be transported across membranes. This mechanism of transport is carried out by specific transporters that have
the ability to transport macromolecules, and regulate organelle function. We have identified new transporters that
are involved in amino acid and protein transport in the mitochondria, chloroplast and peroxisomes. We will assign
function to each protein and investigate the importance in regulating organelle biogenesis. This will allow us to
modulate plant energy production for optimal growth and to withstand abiotic stress, all of which have
agriculturally beneficial consequences. Read moreRead less
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
The Role Of A Presenilin 2 Truncation (PS2V) In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,741.00
Summary
The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for t ....The Presenilin and APP proteins are centrally important in inherited, early onset Alzheimer's disease. We have discovered that a shortened form of Presenilin protein, "PS2V", appears to increase specifically the rate at which the APP protein is cleaved to produce the "Amyloid beta" protein fragment that is found in Alzheimer's disease brains. This occurs when brain cells are under oxidative stress. Understanding this process will facilitate development of appropriate therapeutic strategies for the disease.Read moreRead less
The Role Of Gonadotropins In Regulating The Production Of Alzheimer's Beta Amyloid
Funder
National Health and Medical Research Council
Funding Amount
$400,278.00
Summary
Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause ....Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause or testosterone during andropuase, has been associated with the increased risk of developing AD and in altering the levels of beta amyloid. Furthermore, menopause and andropause are also characterised by changes in other reproductive hormones such as the gonadotropins. High levels of the gonadotropins have also been associated with the increased risk of developing AD. Therefore it is important to identify how these changes modify the risk of developing AD. This study examines the role of the gonadotropins in regulating beta amyloid levels in cell culture and in an animal model for AD. Furthermore, this study will assess, in the animal model, the use of gonadotropin lowering agents to reduce levels of beta amyloid. The results from this study will provide important data on how reproductive hormones regulate beta amyloid. Further insight into these mechanisms will provide therapeutic or preventative strategies for AD.Read moreRead less