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.
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
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
Using Systems Biology To Understand Asthma Exacerbations And Develop Better Treatments
Funder
National Health and Medical Research Council
Funding Amount
$791,734.00
Summary
Our research using cutting-edge technology has demonstrated that not all asthma attacks are the same. There are two major subtypes of asthma attacks. Currently, we use the same medication to treat all asthma attacks, and this medication targets the symptoms rather than the cause. This research will conduct detailed laboratory studies to understand what causes the two different types of asthma attacks, and test new treatments that are targeted and tailored to each type of asthma attack.
Developing Novel Molecules To Down-Regulate Src Family Tyrosine Kinases
Funder
National Health and Medical Research Council
Funding Amount
$201,261.00
Summary
Leukaemia and cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of the common biochemical characteristics of cancer-leukaemia cells is augmented activity levels of enzymes called tyrosine kinases. A major group of tyrosine kinase involved in several cancer-leukaemia types is called the Src family of tyrosine kinases. One member of this family called Lyn has been our focus of study for several years, investigating the signalling ....Leukaemia and cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of the common biochemical characteristics of cancer-leukaemia cells is augmented activity levels of enzymes called tyrosine kinases. A major group of tyrosine kinase involved in several cancer-leukaemia types is called the Src family of tyrosine kinases. One member of this family called Lyn has been our focus of study for several years, investigating the signalling pathways that it is involved in. This molecule has also been implicated in several specific leukaemia (Chronic Myeloid Leukaemia and Acute Myeloid Leukaemia) as well as cancer (Prostate, Colon, Breast) in recent years. We have identified a novel mechanism of down-regulation of this enzyme mediated by an adapter molecule called Cbp, which recruits the Lyn inactivating molecules Csk-Ctk as well as SOCS-1; together they inhibit the activity of Lyn and degrade the enzyme. Using our knowledge of the essential interaction elements of Cbp we will design and test various mini-Cbp molecules for their ability to inactivate and degrade Lyn in leukemic and cancer cells. These molecules may allow us to develop novel therapeutics capable of inactivating-degrading specific tyrosine kinases in cancer and leukaemia.Read moreRead less
Practical application of gene silencing: is delivery of long double stranded ribonucleic acid (dsRNA) by plant cells efficient in conferring host resistance to parasitic nematodes? Nematode that attack plants cause $120 billion of crop losses worldwide. Chemicals used for their control are being phased out because of environmental concerns, and natural resistance is limited. The aim of this project is to use Australian IP to develop a new form of resistance to nematodes based on knowledge of th ....Practical application of gene silencing: is delivery of long double stranded ribonucleic acid (dsRNA) by plant cells efficient in conferring host resistance to parasitic nematodes? Nematode that attack plants cause $120 billion of crop losses worldwide. Chemicals used for their control are being phased out because of environmental concerns, and natural resistance is limited. The aim of this project is to use Australian IP to develop a new form of resistance to nematodes based on knowledge of the host-pathogen interactions. A successful outcome could contribute an additional 5-20% increase in crop yields (depending on the crop) through inherent resistance of crops to nematode pests. This would benefit rural communities and the national economy, and could also generate international royalties.Read moreRead less