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
Discovery Early Career Researcher Award - Grant ID: DE150100517
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Organocatalysis: A New Horizon for Synthesis of Organic Structures. The current technologies to synthesise organic substances, an important part of human life, often involve the use of excess amounts of reagents or precious and toxic metal catalysts, which incur high production costs and severe environmental impact. This project aims to use organocatalysis, chemical processes catalysed by stable, small, easily accessible, non-metallic organic compounds, to find a solution for these issues. Novel ....Organocatalysis: A New Horizon for Synthesis of Organic Structures. The current technologies to synthesise organic substances, an important part of human life, often involve the use of excess amounts of reagents or precious and toxic metal catalysts, which incur high production costs and severe environmental impact. This project aims to use organocatalysis, chemical processes catalysed by stable, small, easily accessible, non-metallic organic compounds, to find a solution for these issues. Novel organocatalytic methods will be designed and developed in order to promote environmentally friendly, highly efficient and selective chemical procedures for low cost production of laboratory organic substances and application in the industrial synthesis of potential agrochemicals and medicinal agents.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
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100104
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Capability for the fabrication and characterisation of mid-infrared photonic materials. The proposed facility will support the development of new glass materials suitable for transmitting and generating light in the mid-infrared spectral region. This research will allow Australia to lead the world in developing new technologies that make use of the mid-infrared region of the electromagnetic spectrum. Particular applications that will flow from this research include the development of new optical ....Capability for the fabrication and characterisation of mid-infrared photonic materials. The proposed facility will support the development of new glass materials suitable for transmitting and generating light in the mid-infrared spectral region. This research will allow Australia to lead the world in developing new technologies that make use of the mid-infrared region of the electromagnetic spectrum. Particular applications that will flow from this research include the development of new optical fibre-based laser sources for defence and surgery, new technologies for detecting and treating cancer, and other in-vivo detection methods.Read moreRead less
Confinement of space based on association of water soluble container molecules. The proposed research addresses the use of water soluble bowl shaped molecules or ions (cavitands) in conjunction with metal ions and crown ether and related cryptand molecules to form molecular capsules, two or more of the components being pre-programmed to assemble thus. The new materials will be unique in supramolecular chemistry, with the associated architectures bearing on materials science, molecular electronic ....Confinement of space based on association of water soluble container molecules. The proposed research addresses the use of water soluble bowl shaped molecules or ions (cavitands) in conjunction with metal ions and crown ether and related cryptand molecules to form molecular capsules, two or more of the components being pre-programmed to assemble thus. The new materials will be unique in supramolecular chemistry, with the associated architectures bearing on materials science, molecular electronics, separation sciences, and drug delivery. The new range of water soluble container molecules that will become accessible as part of this proposal, promises new applications in these areas.Read moreRead less
New Chiral Metal Catalysts; Going Beyond the State of the Art. The synthesis of both natural and unnatural organic compounds in optically active form is a central challenge in chemistry. Because the most important molecules in nature are chiral and of specific handedness, there exists a growing need to access any given organic compound in its optically pure form. Asymmetric catalysis offers the most elegant way to solving this problem and this project will target some of the difficult challenges ....New Chiral Metal Catalysts; Going Beyond the State of the Art. The synthesis of both natural and unnatural organic compounds in optically active form is a central challenge in chemistry. Because the most important molecules in nature are chiral and of specific handedness, there exists a growing need to access any given organic compound in its optically pure form. Asymmetric catalysis offers the most elegant way to solving this problem and this project will target some of the difficult challenges in realising asymmetric synthesis, building new, privileged chiral ligands, opening new catalytic pathways for constructing chiral compounds and understanding the intimate catalytic pathway that enables reactivity and selectivity. This will generate applications across the chemical industries.Read moreRead less
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