Preparation of Photo-Affinity Molecular Probes for the Identification of Gibberellin Receptors. Bioactive gibberellins affect numerous processes during plant growth and development, including seed germination, leaf expansion, stem elongation, flowering and fruit development. However, only very limited information is available regarding their mode of action at the molecular level. The central aim of the project is to prepare a family of photo-affinity molecular probes based on the gibberellin m ....Preparation of Photo-Affinity Molecular Probes for the Identification of Gibberellin Receptors. Bioactive gibberellins affect numerous processes during plant growth and development, including seed germination, leaf expansion, stem elongation, flowering and fruit development. However, only very limited information is available regarding their mode of action at the molecular level. The central aim of the project is to prepare a family of photo-affinity molecular probes based on the gibberellin molecule that will be designed to provide critical information on the location and structure of gibberellin receptors. Screening of the probes for potential effectiveness will be determined initially by the measurement of alpha-amylase produced in a standard barley aleurone assay.Read moreRead less
Biogenesis of secretory organelles and the function of adhesins secreted during the establishment of plant disease. Many agriculturally important crops and Australian native plants are susceptible to diseases caused by species of Phytophthora, a fungus-like organism that lives in the soil. Economic losses due to Phytophthora diseases are estimated to exceed $200 million per annum and the scale of environmental damage in natural ecosystems is huge. Currently, control of Phytophthora diseases la ....Biogenesis of secretory organelles and the function of adhesins secreted during the establishment of plant disease. Many agriculturally important crops and Australian native plants are susceptible to diseases caused by species of Phytophthora, a fungus-like organism that lives in the soil. Economic losses due to Phytophthora diseases are estimated to exceed $200 million per annum and the scale of environmental damage in natural ecosystems is huge. Currently, control of Phytophthora diseases largely depends on a very small number of effective chemicals and there is an imminent risk of the development of pathogen resistance. This research will increase our understanding of how Phytophthora spores infect host plants and will identify suitable targets for the development of novel, environmentally safe chemicals that inhibit disease development.Read moreRead less
Investigating The Physiological And Biochemical Role Of SOCS5 In The Immune System
Funder
National Health and Medical Research Council
Funding Amount
$405,940.00
Summary
Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against paras ....Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against parasite infection. In other words, asthma is thought to arise through inappropriate IL-4 and IL-13 activity in the absence of a parasite infection. Extra IL-13 is commonly found in the lungs of asthmatics and is thought to help trigger asthma attacks. IL-13 is a validated target for drugs that could be used in the treatment of asthma. The SOCS genes were discovered in our laboratory and by genetically deleting the genes in mice we have demonstrated a critical role for SOCS1, SOCS2 and SOCS3 in regulating the immune response and the action of growth hormone. My hypothesis is that SOCS5 is an important physiologic regulator of the asthma response. This proposal will investigate the basic biochemical processes underlying the regulation of IL-4 and IL-13 action and the relationship to development of asthma and immune disease. I plan to induce asthma attacks in mice that lack the genes for SOCS4 and SOCS5. If the severity of the attacks is greater in the absence of these proteins this will indicate that SOCS4 and-or SOCS5 are important negative regulators of IL-4 and IL-13. This has the potential to open up a completely new strategy for the development of drugs that could be used in the prevention and treatment of asthma.Read moreRead less
Targeting of lipid transfer proteins and other secreted plant defence proteins by pathogen effectors. Australia depends on plant products for much of its export income and plant diseases are a continual threat to these earnings. New insights into plant disease resistance mechanisms will provide new opportunities to find solutions to disease problems. Often this involves transfer of knowledge gained in simple model plant systems to more complicated crop plant systems. Work on the role of lipid tr ....Targeting of lipid transfer proteins and other secreted plant defence proteins by pathogen effectors. Australia depends on plant products for much of its export income and plant diseases are a continual threat to these earnings. New insights into plant disease resistance mechanisms will provide new opportunities to find solutions to disease problems. Often this involves transfer of knowledge gained in simple model plant systems to more complicated crop plant systems. Work on the role of lipid transfer proteins in the tomato model system will advance our knowledge of fundamental disease and disease resistance processes and ultimately enable technological innovations to improve disease resistance, reduce pesticide usage and lower crop production costs.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
Sorting Nexins And Their Role In Endosomal Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$331,000.00
Summary
Cells are able to internalise molecules via membrane-bound vesicles, a process known as endocytosis. Endocytosis is fundamental for many cellular processes, including receptor signalling, uptake of many essential nutrients and the ability to mount an effective lymphocyte response to foreign antigens. Once internalised, cargo is then sorted to different intracellular destinations of the endosomal transport system. The ultimate destination depends on the particular cargo molecule. The importance o ....Cells are able to internalise molecules via membrane-bound vesicles, a process known as endocytosis. Endocytosis is fundamental for many cellular processes, including receptor signalling, uptake of many essential nutrients and the ability to mount an effective lymphocyte response to foreign antigens. Once internalised, cargo is then sorted to different intracellular destinations of the endosomal transport system. The ultimate destination depends on the particular cargo molecule. The importance of the endosomal transport system is also highlighted by the discovery that many human diseases, including various cancers, lysosomal storage diseases and hypercholesterolemia, are linked to defects in trafficking along the endocytic pathway. Furthermore, a number of viral pathogens, such as HIV, and toxins, such as shiga toxin, exploit the endosomal system to gain entry into a cell. Understanding the molecular details of the sorting events within the endosomal system is necessary to be able to consider therapeutic manipulation of the trafficking of specific cargo molecules. The study seeks to understand the molecular details of the endosomal sorting machinery, knowledge that will underpin future efforts to develop drugs to manipulate movement of proteins within the endosomal system. In the long term, this could allow for the manipulation of a variety of cellular functions including the inhibition of proliferative signals in tumour cells.Read moreRead less
The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of ....The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of macropinocytosis at a molecular level. The project is relevant to understanding the functioning of normal cells and the means by which some pathogens can enter cells and also understanding processes involved in tumour progression and metastasis.Read moreRead less
Determination of the mechanisms of immune system regulation of inflammation by the human protein, chaperonin 10. The aim of this project is to determine the mechanisms by which a human protein, chaperonin 10 (Cpn10), regulates the immune system and suppresses inflammation. When cells of the human immune system are challenged with lipopolysaccharide (LPS) (a product of bacterial infection), the pro-inflammatory cytokine TNF is released. Cpn10 has been shown to suppress production of TNF on chall ....Determination of the mechanisms of immune system regulation of inflammation by the human protein, chaperonin 10. The aim of this project is to determine the mechanisms by which a human protein, chaperonin 10 (Cpn10), regulates the immune system and suppresses inflammation. When cells of the human immune system are challenged with lipopolysaccharide (LPS) (a product of bacterial infection), the pro-inflammatory cytokine TNF is released. Cpn10 has been shown to suppress production of TNF on challenge of cells with LPS, while increasing the levels of the anti-inflammatory cytokine IL-10. Investigating the role of Cpn10 in modulating inflammation will contribute to the understanding and treatment of diseases associated with inflammation, including multiple sclerosis and rheumatoid arthritis.Read moreRead less