Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for ....Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for simultaneously examining the expression patterns of every gene in the model plant Arabidopsis, this project will identify proteins that regulate mitochondrial biosynthesis and uncover the gene networks that these proteins control. The project outcomes will provide new opportunities for the rational manipulation of plant growth and productivity.Read moreRead less
Arabidopsis DNA binding proteins that control transcription of its mitochondrial genome. The increases in crop output and quality needed to drive the agricultural sector of Australia's future economy will arise from knowledge gained by combining traditional methods and the type of cutting-edge research that identifies plant mitochondrial DNA-binding proteins and their sites of action. Mitochondria are fundamental to many agronomically important traits, including plant growth, fruit ripening and ....Arabidopsis DNA binding proteins that control transcription of its mitochondrial genome. The increases in crop output and quality needed to drive the agricultural sector of Australia's future economy will arise from knowledge gained by combining traditional methods and the type of cutting-edge research that identifies plant mitochondrial DNA-binding proteins and their sites of action. Mitochondria are fundamental to many agronomically important traits, including plant growth, fruit ripening and plant stress and disease defence. Opportunities for the rational manipulation of these and hitherto undiscovered traits will come from new knowledge generated by this project, which will develop and use frontier technologies that will keep Australia at the forefront of international research into mitochondrial structure and function.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.
Characterization Of Novel Regulators Of Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature fu ....Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature functional cells. We have identified six molecules which interact with Lyn in red blood cells. We have shown that amolecule called HS1 is important for epo function in individual red blood cells and now we plan to investigate its functions in whole animals, including mice that lack the HS1 gene. We have also shown that a molecule called Trip1 is important for red blood cell development. Interestingly, this molecule also interacts with the thyroid hormone receptor and can influence the effects of epo and thyroid hormone on red blood cell development. The interplay between these two hormones will be looked at in more detail both at the cell and whole animal levels in normal mice and those lacking the thyroid hormone receptor gene. The third Lyn binding molecule we isolated is a novel gene-we have named it ankyrin repeat protein in line with the molecules it is related to. This gene is expressed in red blood cells and we aim to investigate what role it plays in the development of these cells. The fourth gene is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Its role in red blood cell structure will also be investigated. Finally, the last two molecule we have identified are both novel and are unrelated to any other known proteins. As above, the effects of these two molecules on red blood cell development will be investigated.Read moreRead less
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
ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.Read moreRead less
Engineering synthetic genetic codes. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides ....Engineering synthetic genetic codes. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides an opportunity to put the future of drug discovery in the hands of the wider scientific community and new tools for Australian industries.Read moreRead less
Re-engineering the genetic code. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides an o ....Re-engineering the genetic code. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides an opportunity to put the future of drug discovery in the hands of the wider scientific community and provides new tools for Australian industries.Read moreRead less
Waxing And Waning Of Asthma During Transition From The Teens To Adulthood: Identification Of Immunophenotypic Markers To Predict Disease Trajectory And Guide Development Of Treatment Strategies To Prevent Progression To Chronicity
Funder
National Health and Medical Research Council
Funding Amount
$736,166.00
Summary
The project will seek to identify biomarkers in teenage/young adult asthmatics that can distinguish between those who are "growing out" of the disease, versus those who are progressing towards chronic severe asthma. This knowledge will inform the development of more effective treatment programs for this age group.
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