Ubiquinone in Giardia: Amitochondrial component in an amitochondriate parasite. Giardia intestinalis is a fascinating organism, it is one of the most primitive nucleated organisms known and is responsible for ~280 million infections annually. Ubiquinone is usually associated with mitochondrial function, however it has been found in Giardia, which lacks this organelle. Our initial studies show that in Giardia, ubiquinone plays essential roles in electron transport pathways associated with membr ....Ubiquinone in Giardia: Amitochondrial component in an amitochondriate parasite. Giardia intestinalis is a fascinating organism, it is one of the most primitive nucleated organisms known and is responsible for ~280 million infections annually. Ubiquinone is usually associated with mitochondrial function, however it has been found in Giardia, which lacks this organelle. Our initial studies show that in Giardia, ubiquinone plays essential roles in electron transport pathways associated with membrane energisation and oxidative stress management. Elucidation of these mechanisms will have a major impact on the understanding of Giardia and other anaerobic organisms as well as being of significant evolutionary and medical importance.
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In situ measurements of the electrostatic properties inside photosynthetic reaction centres: correlation with the energy conversion function of the protein. The photochemical reaction centre is a key protein complex involved in energy conversion. It converts solar energy into chemical energy as a transmembrane charge separation. Coupling of electron and proton transfer is catalysed at the level of a ubiquinone cofactor. In order to understand how the redox properties of this cofactor are fine tu ....In situ measurements of the electrostatic properties inside photosynthetic reaction centres: correlation with the energy conversion function of the protein. The photochemical reaction centre is a key protein complex involved in energy conversion. It converts solar energy into chemical energy as a transmembrane charge separation. Coupling of electron and proton transfer is catalysed at the level of a ubiquinone cofactor. In order to understand how the redox properties of this cofactor are fine tuned by the protein environment, we plan to probe the ubiquinone site using a voltage-sensitive fluorescent dye. This exciting multidisciplinary project will contribute to the understanding of how protein matrices influence and govern the midpoint redox potential of their cofactors and the environments of theirRead moreRead less
Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical int ....Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical intervention. In addition, a powerful model system for studies of ER protein aggregation will be established, high-level training in biochemistry and morphometry will be provided, and an international collaboration of the highest calibre will be initiated.Read moreRead less
Heparan sulfate proteoglycan from smooth muscle cell basal lamina: It's role in cell signalling. Heart disease is the major killer of people in the Western world. central to this disease is the killing of heart muscle tissue to it being starved of oxygen via a "heart attack". One of the common treatments is coronary artery bypass surgery, however, the supply of vessels that can be used is limited. In order to provide an alternative supply of vessels, we are aiming to engineer blood vessels i ....Heparan sulfate proteoglycan from smooth muscle cell basal lamina: It's role in cell signalling. Heart disease is the major killer of people in the Western world. central to this disease is the killing of heart muscle tissue to it being starved of oxygen via a "heart attack". One of the common treatments is coronary artery bypass surgery, however, the supply of vessels that can be used is limited. In order to provide an alternative supply of vessels, we are aiming to engineer blood vessels in the laboratory. The major cell of the wall of arteries, the smooth muscle cell, is critical to normal functioning and integration of these transplanted arteries. To do this we will need to understand the cell signalling responses of these cells in relation to molecules in their surrounding environment.Read moreRead less
Identification of structural proteins in the tissue cyst wall of Toxoplasma gondii. Most infections with Toxoplasma gondii are asymptomatic, however, infection during pregnancy can lead to miscarriage or blindness, deafness and mental retardation in the developing baby. Furthermore, in AIDS patients, toxoplasmosis is the leading cause of fatal encephalitis as the normally dormant tissue cysts are reactivated in the absence of an effective immune system. In Australia, it has been estimated that ~ ....Identification of structural proteins in the tissue cyst wall of Toxoplasma gondii. Most infections with Toxoplasma gondii are asymptomatic, however, infection during pregnancy can lead to miscarriage or blindness, deafness and mental retardation in the developing baby. Furthermore, in AIDS patients, toxoplasmosis is the leading cause of fatal encephalitis as the normally dormant tissue cysts are reactivated in the absence of an effective immune system. In Australia, it has been estimated that ~30% of the population is infected with T. gondii and the occurrence of congenital toxoplasmosis is 0.2% of live births, which translates to roughly 500 cases/year. Our research will identify structural proteins in Toxoplasma cyst walls that will lead to the design of new strategies to control the diseases caused by these parasites.Read moreRead less
The effects of alpha-2-macroglobulin on amyloid formation and toxicity. The expected outcomes will provide major advances in understanding how the abundant human blood protein alpha-2-macroglobulin influences the formation of protein aggregates that underpin a number of serious diseases (e.g. Alzheimer's disease). The linkages involved are of the highest calibre and will give the Fellowship holder a unique opportunity for training in environments that are truly internationally leading-edge. Fur ....The effects of alpha-2-macroglobulin on amyloid formation and toxicity. The expected outcomes will provide major advances in understanding how the abundant human blood protein alpha-2-macroglobulin influences the formation of protein aggregates that underpin a number of serious diseases (e.g. Alzheimer's disease). The linkages involved are of the highest calibre and will give the Fellowship holder a unique opportunity for training in environments that are truly internationally leading-edge. Furthermore, the very high novelty and broad significance of this work indicate that it will produce high-impact publications which will tangibly assist Australia being recognized as a major contributor to international research outcomes of the highest quality.Read moreRead less
Biomolecular surface interactions with smart biomaterials. Current materials used for medical implants are often recognised by the body as foreign materials causing implant rejection or encapsulation. Research into the interactions between biological molecules and chemically and topographically modified materials will aid in the development of new materials and devices that optimise the body's response to the implanted material. The new materials and surfaces developed from this research will pr ....Biomolecular surface interactions with smart biomaterials. Current materials used for medical implants are often recognised by the body as foreign materials causing implant rejection or encapsulation. Research into the interactions between biological molecules and chemically and topographically modified materials will aid in the development of new materials and devices that optimise the body's response to the implanted material. The new materials and surfaces developed from this research will provide longer lasting implants and reduce the need for repeated operations. This will improve the quality of life for implant recipients and reduce health care costs.Read moreRead less
Dynamic signaling pathways of dispersal in bacterial biofilms. This Breakthrough Science project will result in an increased understanding of the molecular processes that govern biofilm development and dispersal. While the outcomes will be directly applicable where P. aeruginosa infections continue to cause health-threatening conditions, such as in Cystic Fibrosis chronic infections, it will also be instrumental for the rational design of novel products and strategies to control biofilms of othe ....Dynamic signaling pathways of dispersal in bacterial biofilms. This Breakthrough Science project will result in an increased understanding of the molecular processes that govern biofilm development and dispersal. While the outcomes will be directly applicable where P. aeruginosa infections continue to cause health-threatening conditions, such as in Cystic Fibrosis chronic infections, it will also be instrumental for the rational design of novel products and strategies to control biofilms of other single species or of mixed species populations in many other settings. Countless environmental, industrial and clinical applications will benefit from improved antimicrobial strategies and reduced usage of antibiotics.Read moreRead less
Interfacial interactions with hydrogel biomaterials. The interactions between cells of the body and the surfaces of medical implants are controlled largely by the molecules that are adsorbed on the surface. The aim of this project is to evaluate the effect of modifying hydrogel biomaterials on the interactions of the molecules with the hydrogel. This, in turn, allows us to determine the factors affecting the control of the cell's response. The significance of this work is in the improved ability ....Interfacial interactions with hydrogel biomaterials. The interactions between cells of the body and the surfaces of medical implants are controlled largely by the molecules that are adsorbed on the surface. The aim of this project is to evaluate the effect of modifying hydrogel biomaterials on the interactions of the molecules with the hydrogel. This, in turn, allows us to determine the factors affecting the control of the cell's response. The significance of this work is in the improved ability to control cellular responses to implants. Such improved response will result in better health outcomes for patients, and outcomes in the form of papers and intellectual property.
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Single Molecule Studies of Replisomal Function. It has recently become possible to watch the copying of DNA molecules with a specialized microscope in real time. This process requires assembly of a complex molecular machine on the DNA, followed by triggering of its function, and yields exquisitely detailed information about how the machine works. In this new collaboration between scientists in Australia and the U.S.A., we will assemble these machines on single DNA molecules, watch how they work ....Single Molecule Studies of Replisomal Function. It has recently become possible to watch the copying of DNA molecules with a specialized microscope in real time. This process requires assembly of a complex molecular machine on the DNA, followed by triggering of its function, and yields exquisitely detailed information about how the machine works. In this new collaboration between scientists in Australia and the U.S.A., we will assemble these machines on single DNA molecules, watch how they work and simultaneously measure the very small forces that the machines generate. This will give Australian scientists access to a new technology for studying molecular machines.Read moreRead less