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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
Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesi ....Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesis of inhibitors of these enzymes.Read moreRead less
Matched experiments and numerical simulations of flow-induced oscillations in uniform and tapered-stiffness collapsible tubes. Flexible tubes that can be flattened are widespread in the body and can act to limit flow-rate. Limitation is usually associated with spontaneous oscillation (repetitive opening and closing). There are many candidate explanations, but none has been shown to correspond with a given experiment. Through computer models and matched experiments on this coupled system (the ....Matched experiments and numerical simulations of flow-induced oscillations in uniform and tapered-stiffness collapsible tubes. Flexible tubes that can be flattened are widespread in the body and can act to limit flow-rate. Limitation is usually associated with spontaneous oscillation (repetitive opening and closing). There are many candidate explanations, but none has been shown to correspond with a given experiment. Through computer models and matched experiments on this coupled system (the fluid flow interacts with the tube shape), we seek to demonstrate for the first time that a given theory/computer model encompasses the physics controlling a given observed oscillation. The solution will find application in other flexible-structure design problems in engineering, and also potentially in medicine.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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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
Biomaterial applications of synthetic elastin. The grant will develop a new collaboration between two established laboratories. The Weiss Lab (synthetic elastin; University of Sydney, Australia) will send elastin materials to the Langer Lab (interface of biotechnology and materials science; MIT, USA). Prof. Weiss will visit the Langer Lab and be trained in and participate collaboratively in the use of established MIT methodologies that will focus on applications in cardiac tissue engineering, co ....Biomaterial applications of synthetic elastin. The grant will develop a new collaboration between two established laboratories. The Weiss Lab (synthetic elastin; University of Sydney, Australia) will send elastin materials to the Langer Lab (interface of biotechnology and materials science; MIT, USA). Prof. Weiss will visit the Langer Lab and be trained in and participate collaboratively in the use of established MIT methodologies that will focus on applications in cardiac tissue engineering, controlled release of drugs and vocal fold repair. The MIT group will benefit from access to and the use of elastin materials that are developed in AustraliaRead 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