Cytoprotection By Erythropoietin In Hypoxia-ischaemia Of The Kidney And Brain
Funder
National Health and Medical Research Council
Funding Amount
$477,661.00
Summary
We aim to make a significant research impact by describing the complex mechanisms responsible for protecting kidney and brain cells from stress caused by a lack of oxygen. In particular we will establish whether the compound erythropoietin (Epo), which occurs naturally in the human body but its human recombinant form can also be used as a treatment, may be useful in protecting cells from death following a shortage of oxygen. . We have already described how Epo can protect the kidney, but no one ....We aim to make a significant research impact by describing the complex mechanisms responsible for protecting kidney and brain cells from stress caused by a lack of oxygen. In particular we will establish whether the compound erythropoietin (Epo), which occurs naturally in the human body but its human recombinant form can also be used as a treatment, may be useful in protecting cells from death following a shortage of oxygen. . We have already described how Epo can protect the kidney, but no one has yet described its action on kidney cell differentiation or its effect on structural and vascular support in the injured kidney. When might Epo treatment be effective? Could it protect against chronic renal disease? Likewise, whilst more very pre-term babies survive, this is a crucial period when they are at heightened sensitivity to lack of oxygen and they are at risk of brain damage and poor development because of lack of maturation of key structural cells in the brain. The role of Epo in aiding brain cell maturation and on blood vessel formation and function in this faulty development period is not known. Both of these health problems are major issues causing huge costs to society both financial and emotional. Despite the early evidence of a useful role for Epo in human disease treatment, current experimental and clinical data demonstrate the importance of further thorough investigation of mechanisms and cellular pathways that will underpin improvements in clinical outcomes. A particular strength of our project is that by comparing similarities and differences in the kidney and brain, we will be able to elucidate the mechanisms of action of Epo and its analogues.Read moreRead less
Proteome mapping of the model fungal plant pathogen Stagonospora nodorum using LC-LC-MS/MS. Stagonospora nodorum is a fungus that causes leaf and glume blotch disease on wheat. This disease alone causes $55 million dollars in yield losses per annum in Australia. This project aims to identify the proteins produced by Stagonospora nodorum through the development of a new proteomics technique. Two clear benefits to the community resulting from this project will emerge. The first will be the expert ....Proteome mapping of the model fungal plant pathogen Stagonospora nodorum using LC-LC-MS/MS. Stagonospora nodorum is a fungus that causes leaf and glume blotch disease on wheat. This disease alone causes $55 million dollars in yield losses per annum in Australia. This project aims to identify the proteins produced by Stagonospora nodorum through the development of a new proteomics technique. Two clear benefits to the community resulting from this project will emerge. The first will be the expert training of a student in proteomics, a skill that is keenly sought. Secondly, the identification of these pathogen proteins will lead to new strategies to better control the disease and secure the supply of wheat.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100078
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Multiphoton confocal microscope. Recent developments in light microscopy have revolutionised modern molecular and cellular biology. Dramatic improvements in microscope hardware and software and in the range of fluorescent markers used to tag selected cellular components now provide new and exciting opportunities to localise and determine the function of ions and molecules not only in preserved samples but also, most excitingly, in living cells. The proposed multiphoton confocal microscope will ....Multiphoton confocal microscope. Recent developments in light microscopy have revolutionised modern molecular and cellular biology. Dramatic improvements in microscope hardware and software and in the range of fluorescent markers used to tag selected cellular components now provide new and exciting opportunities to localise and determine the function of ions and molecules not only in preserved samples but also, most excitingly, in living cells. The proposed multiphoton confocal microscope will allow researchers in Canberra to obtain high quality images of static and moving components in living cells and tissues and will facilitate the discovery of new knowledge that contributes to our understanding and control of development and disease in both plants and animals.Read moreRead less
Molecular characterisation of the Prf bacterial recognition complex of tomato. This project will investigate the composition and function of a large protein complex in tomatoes that controls their ability to resist attack by bacteria. The results will provide understanding to how all plants resist all diseases, and may help to improve environmentally-benign disease resistance in crop species.
Establishing the role of heterotrimeric G-proteins in plant defence. Agriculture is an important economic activity in Australia that resulting in considerable export revenues. Agricultural losses caused by plant pathogens account for millions of dollars every year and have profound economic and social implications.
The proposed research will explore new approaches to increase plant resistance to pathogens using a previously unkown component of this network: G-proteins and could ultimately reduc ....Establishing the role of heterotrimeric G-proteins in plant defence. Agriculture is an important economic activity in Australia that resulting in considerable export revenues. Agricultural losses caused by plant pathogens account for millions of dollars every year and have profound economic and social implications.
The proposed research will explore new approaches to increase plant resistance to pathogens using a previously unkown component of this network: G-proteins and could ultimately reduce dependency on toxic chemical products.Read moreRead less
The development of mass spectrometry techniques for mapping post-translational modifications in the wheat pathogen Stagonospora nodorum. The fungus Stagonospora nodorum is a significant pathogen of wheat causing in excess of $100 million dollars in yield losses per annum in Australia. This project will develop new analytical methods that can be used to detect important protein modifications in Stagonospora nodorum with the goal of securing Australia's wheat supply.
Biosynthesis and functions of two phytotoxins in Septoria nodorum blotch. This project aims to investigate how a fungal plant pathogen makes and uses small bioactive molecules to facilitate infection. It will characterise the function of the genes and enzymes involved in the biosynthesis of a light-activated phytotoxic molecule and a potential anti-plant defence molecule found in the pathogenic wheat fungus Parastagonospora nodorum, and investigate their contribution to disease development. Expe ....Biosynthesis and functions of two phytotoxins in Septoria nodorum blotch. This project aims to investigate how a fungal plant pathogen makes and uses small bioactive molecules to facilitate infection. It will characterise the function of the genes and enzymes involved in the biosynthesis of a light-activated phytotoxic molecule and a potential anti-plant defence molecule found in the pathogenic wheat fungus Parastagonospora nodorum, and investigate their contribution to disease development. Expected outcomes include better understanding of plant-microbe interactions, disease management strategies, technologies for identifying biosynthetic pathways in other fungi, and enzyme technology for synthesising molecules. This could lead to new herbicides, biopesticides and drugs.Read moreRead less
Fungal Ribosomally Synthesised and Post-translationally Modified Peptides. Fungi produce an array of molecules called secondary metabolites (SMs) that impact on everyday life (e.g. penicillin). This project aims to investigate a new class of fungal peptide SMs called RiPPs which are structurally unique from existing molecules and offer the exciting prospect of harbouring new and novel biological activities. This project expects to discover the mechanisms of RiPP synthesis and their biological ro ....Fungal Ribosomally Synthesised and Post-translationally Modified Peptides. Fungi produce an array of molecules called secondary metabolites (SMs) that impact on everyday life (e.g. penicillin). This project aims to investigate a new class of fungal peptide SMs called RiPPs which are structurally unique from existing molecules and offer the exciting prospect of harbouring new and novel biological activities. This project expects to discover the mechanisms of RiPP synthesis and their biological roles in plant pathogenic fungi, and uncover and engineer novel RiPPs with desired bioactivities. The expected outcome from this project will be a seminal advance in fungal SM biology which should provide significant benefits through the generation of exciting new lead molecules for the agricultural and medical industries.Read moreRead less
Pathophysiological mechanisms in equine dyschondroplasia (osteochondrosis). Dyschondroplasia (osteochondrosis) is a developmental orthopaedic disease of horses, which causes significant wastage within the Thoroughbred racing industry. The disease affects growth cartilage beneath joint surfaces in such a way that cartilage fails to be replaced by bone, resulting in defects in the joint surface and lameness. This project will identify differences in gene expression between normal cartilage and ea ....Pathophysiological mechanisms in equine dyschondroplasia (osteochondrosis). Dyschondroplasia (osteochondrosis) is a developmental orthopaedic disease of horses, which causes significant wastage within the Thoroughbred racing industry. The disease affects growth cartilage beneath joint surfaces in such a way that cartilage fails to be replaced by bone, resulting in defects in the joint surface and lameness. This project will identify differences in gene expression between normal cartilage and early dyschondroplastic lesions, in order to identify the sequence of molecular events leading to induction of disease. The basic understanding of joint development obtained from this work will assist in the development of strategies to prevent and diagnose dyschondroplasia in horses.Read moreRead less
Selective secretion: a novel mechanism of protein trafficking and its role in Phytophthora pathogenicity. Agriculturally important crops and over 3,000 Australian native plants are susceptible to diseases caused by Phytophthora, fungus-like pathogens that live in the soil. Economic losses exceed $200m pa and natural ecosystems are being destroyed on a vast scale. Phytophthora control depends upon a limited number of chemical inhibitors to which resistance has already emerged. New control stra ....Selective secretion: a novel mechanism of protein trafficking and its role in Phytophthora pathogenicity. Agriculturally important crops and over 3,000 Australian native plants are susceptible to diseases caused by Phytophthora, fungus-like pathogens that live in the soil. Economic losses exceed $200m pa and natural ecosystems are being destroyed on a vast scale. Phytophthora control depends upon a limited number of chemical inhibitors to which resistance has already emerged. New control strategies are urgently needed. This research will investigate a novel mechanism for release of infection material recently discovered in Phytophthora cells, and will increase our understanding of how Phytophthora infects host plants, providing vital information required for the development of new, environmentally-safe inhibitors. Read moreRead less