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The Role Of Copper In Ubiquitin-dependent Protein Degradation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
Ubiquitin’s are small proteins that tag other proteins in a process known as “Ubiquitination”. Often this is to target them for degradation once they are no longer needed i.e. to take out the rubbish. This process is disrupted in Alzheimer’s disease (AD), which may contribute to the disease. This project aims to find out if copper, an essential metal for life, is required for this process. Drugs that are designed to deliver copper to brain cells have been effective in small AD clinical trials.
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
Erythroid Molecular Cascades Involving The Tyrosine Kinase Lyn
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Mature red and white cells develope 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 functio ....Mature red and white cells develope 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. Recently, we have demonstrated that mice lacking the Lyn gene develope major problems with their red blood cells. We have identified several molecules which interact with Lyn in red blood cells. We have shown that a molecule called Cbp is important for Epo function in individual red blood cells and now we plan to investigate its function in whole animals. We have shown that a new molecule called Arp is important for red blood cell development. This protein moves in and out of the nucleus (where DNA is stored) and may be important in the regulation of genes needed for red blood cells. The third gene (AFAPbeta) is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Since red blood cells have to shrink considerably during their development, the role of AFAPbeta on red blood cell structure will also be investigated. From these experiments we should develop a much better understanding of how the production of red blood cells is controlled and how diseases of red blood cells (such as anaemia) occur.Read moreRead less
Role of organic matter in soil pH change in agro-ecosystems. Over 50 million hectares of arable lands in Australia are affected by soil acidity. Acidity-affected lands continue to expand due to the ongoing process of acidification under current farming practices. The project will provide new knowledge essential for the improved use and management of organic matter to minimize or reverse soil acidification and increase carbon sequestration in farming systems. The associated reduction of soil aci ....Role of organic matter in soil pH change in agro-ecosystems. Over 50 million hectares of arable lands in Australia are affected by soil acidity. Acidity-affected lands continue to expand due to the ongoing process of acidification under current farming practices. The project will provide new knowledge essential for the improved use and management of organic matter to minimize or reverse soil acidification and increase carbon sequestration in farming systems. The associated reduction of soil acidification will also minimise the negative impact of nutrient and water losses on the environment. Growers will benefit from the project through improved soil fertility and crop production, and sustainable land use. Read moreRead less
Stabilisation of erodible and dispersive soils with natural wood processing by-products. Lignosulfonate is a by-product of paper and wood processing industry, which is an environmentally friendly organic compound with an immense potential for stabilising erodible and dispersive soils when mixed in small quantities. This project will deliver practical design guidelines and specifications for sustainable performance of road and rail embankments that are treated with lignosulfonates. Utilisation of ....Stabilisation of erodible and dispersive soils with natural wood processing by-products. Lignosulfonate is a by-product of paper and wood processing industry, which is an environmentally friendly organic compound with an immense potential for stabilising erodible and dispersive soils when mixed in small quantities. This project will deliver practical design guidelines and specifications for sustainable performance of road and rail embankments that are treated with lignosulfonates. Utilisation of lignosulfonates in soil stabilisation is not only cost-effective, but also has the benefit of eliminating a waste disposal problem. The proposed project will improve industrial competitiveness and Australia's export earnings through increased commercialisation and technology transfer in the region.Read moreRead less
Assessing soil formation and erosion balances in the Top End with an expanded toolkit. This work is timely as it will provide the tools and the data to assess the sustainability with regard to soil loss of potential agricultural development in the Top End of Australia. With food-growing areas in southern Australia under stress from a prolonged drought, the Federal Government has established a Northern Australia Land and Water Taskforce to explore the potential of the Top End for agricultural and ....Assessing soil formation and erosion balances in the Top End with an expanded toolkit. This work is timely as it will provide the tools and the data to assess the sustainability with regard to soil loss of potential agricultural development in the Top End of Australia. With food-growing areas in southern Australia under stress from a prolonged drought, the Federal Government has established a Northern Australia Land and Water Taskforce to explore the potential of the Top End for agricultural and other development. A key component of its brief is that development must be sustainable. The economic consequences of increased agriculture in the North are likely to be profound, and the findings of this research will be crucial to success.Read moreRead less
Theoretically derived calibration of the neutron moisture meter. The moisture content of soils is of key importance in a wide range of situations including agriculture, engineering and land and water management. The measurement of soil moisture contents in the field is problematic, and even commonly used methods like the neutron probe give results of limited accuracy. This research will enable calibration curves for the neutron probe to be determined theoretically, thereby improving the accuracy ....Theoretically derived calibration of the neutron moisture meter. The moisture content of soils is of key importance in a wide range of situations including agriculture, engineering and land and water management. The measurement of soil moisture contents in the field is problematic, and even commonly used methods like the neutron probe give results of limited accuracy. This research will enable calibration curves for the neutron probe to be determined theoretically, thereby improving the accuracy of moisture content measurements and enhancing its usefulness to industry and research.Read moreRead less
Directed Molecular Evolution Of G Protein-coupled Receptors For Stable And Functional Expression In Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$383,479.00
Summary
Approximately half of all prescription drugs on the market act on G protein coupled receptors (GPCRs). The mechanisms underlying GPCR function are mainly unknown due to a lack of structural information. No solved structures exist for any of the estimated 800 human GPCRs, making it difficult to design new drugs. By applying advanced protein engineering techniques I aim to produce human GPCRs in bacteria to ultimately acquire structural information, which will enable novel drug development.
Production and transport of soil and sediments, determined by cosmogenic radionuclides and noble gases. Basic questions concerning Australia's soil and regolith resources are addressed through measurement of nuclides produced by cosmic rays in near-surface minerals. Cosmogenic Be-10, Ne-21 and Al-26 are used to (i) quantify the sustainable levels of soil loss, (ii) assess long-term mixing rates, (iii) quantify dispersion and flux of regolith materials from hill-slopes to rivers, and (iv) determi ....Production and transport of soil and sediments, determined by cosmogenic radionuclides and noble gases. Basic questions concerning Australia's soil and regolith resources are addressed through measurement of nuclides produced by cosmic rays in near-surface minerals. Cosmogenic Be-10, Ne-21 and Al-26 are used to (i) quantify the sustainable levels of soil loss, (ii) assess long-term mixing rates, (iii) quantify dispersion and flux of regolith materials from hill-slopes to rivers, and (iv) determine the rates of sediment movement through Australian rivers and floodplains, including sediment-adsorbed pollutants. The research has strong implications for the usage and conservation of soil, sediments and weathered deposits for agriculture, mineral resources, and sedimentary waste disposal.Read moreRead less
Spatial and temporal monitoring of soil erosion risk with satellite imagery. This project is directed towards Sustainable farm practices, one of the national priorities in the Caring for Our Country program. The satellite image-based monitoring system will provide new information about the changing distribution of erosion risk in seasonal cropping systems, and identify areas where agricultural practices significantly influence this risk. The research will allow landholders, regional, state and n ....Spatial and temporal monitoring of soil erosion risk with satellite imagery. This project is directed towards Sustainable farm practices, one of the national priorities in the Caring for Our Country program. The satellite image-based monitoring system will provide new information about the changing distribution of erosion risk in seasonal cropping systems, and identify areas where agricultural practices significantly influence this risk. The research will allow landholders, regional, state and national authorities to better target effort towards sustainable land management, and improve monitoring and reporting of land condition across broad agricultural regions. Dynamic monitoring of erosion risk will also track landscape conditions and farmer responses to changing climate.Read moreRead less