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Enhancing The Cardioprotective Effect Of Diadenosine Tetraphosphate: Designing Inhibitors Against Ap4A Hydrolase
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitocho ....Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitochondrial ATP-dependent potassium channel may be in common with most pathways. Pretreatment with the compound diadenosine tetraphosphate (Ap4A) mimics ischemic preconditioning with noticeable reductions in tissue necrosis (cell death). This treatment has been shown in experimental work to protect the heart during periods of stress such as in heart surgery or recovery from an ischemic event. The biological site of action by Ap4A may be the mitochondria ATP-dependent potassium channel or an associated protein. Ap4A can be degraded by enzymes located inside and on the outside of heart cells, notably by two forms of Ap4A hydrolase. We will use antibody assays to understand the specific localization and amount of Ap4A hydrolase before and after ischemia and after ischemic preconditioning in human heart muscle and blood vessels. We propose to determine the structure of the enzyme and use novel computer methods to screen databases for potential inhibitors. These inhibitors of Ap4A hydrolase activity could aid the design of a potent inhibitor that would prevent Ap4A hydrolase from degrading Ap4A and therefore enhance the cardioprotective properties of Ap4A as well as minimizing side effects from the break down of Ap4A. We will also use these inhibitors and other known non-degradable Ap4A analogues in bioassays to test the relative significance of Ap4A hydrolase present in different cellular locations.Read moreRead less
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less
Towards A New Class Of Reverse Transcriptase Inhibitor For HIV Prevention
Funder
National Health and Medical Research Council
Funding Amount
$688,833.00
Summary
There remains an urgent need for new HIV prevention strategies. New HIV drugs that block the virus by distinct ways are needed to prevent transmission of drug resistant HIV. This study seeks to identify very small molecules called “fragments” that bind to previously undiscovered pockets on the HIV reverse transcriptase to stop its function, and that can be used as building blocks to design more potent HIV drugs to be used solely for HIV prevention.
Discovery Early Career Researcher Award - Grant ID: DE190100113
Funder
Australian Research Council
Funding Amount
$420,437.00
Summary
Interactions between volumetric units in modular buildings. This project aims to develop an in-depth understanding of the interactions between volumetric units in modular buildings to develop integration strategies for the interconnection of modules. The uptake of modular construction has been hindered by the technical complexities of the design process for manufacture and assembly, in particular the flexible connection of services. By addressing significant gaps in the guidance on the design of ....Interactions between volumetric units in modular buildings. This project aims to develop an in-depth understanding of the interactions between volumetric units in modular buildings to develop integration strategies for the interconnection of modules. The uptake of modular construction has been hindered by the technical complexities of the design process for manufacture and assembly, in particular the flexible connection of services. By addressing significant gaps in the guidance on the design of modular interconnections and their integration strategies, this project expects to enhance the industry’s capacity to adopt safe, economical and standardised designs of modular systems. This project should significantly reduce the risk in decision making in modular construction, and transformation to advanced building manufacturing technologies in Australia and beyond.Read moreRead less
Surfacing urban wetlands in two urban renewal sites in Sydney. Urban wetlands in Australia provide benefits for climate change mitigation, pollution reduction, habitat provision and socioecological connection. However, in large cities like Sydney, urban wetlands are unseen because undergrounded, and, therefore not adequately understood. This illegibility, and loss of understanding by residents, planners and policy makers impedes wetlands' good management. This project surfaces wetlands through v ....Surfacing urban wetlands in two urban renewal sites in Sydney. Urban wetlands in Australia provide benefits for climate change mitigation, pollution reduction, habitat provision and socioecological connection. However, in large cities like Sydney, urban wetlands are unseen because undergrounded, and, therefore not adequately understood. This illegibility, and loss of understanding by residents, planners and policy makers impedes wetlands' good management. This project surfaces wetlands through visualisation in a multimodal knowledge platform focusing on two urban renewal sites, Green Square and Marrickville South. We leverage design ethnography to develop resources for strengthening multiple stakeholders’ socioecological engagement through methods empowering just, creative and open participation.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100161
Funder
Australian Research Council
Funding Amount
$407,598.00
Summary
Translational Design: Product Development for Research Commercialisation. Australia is a world leader in fundamental research. Yet, ranks as one of the worst developed nations for translating research into new-to-market innovation. This project explores a new role for design as a critical component of research commercialisation and innovation ecosystems. It expects to contribute novel insights into how designers can be better integrated into interdisciplinary research directed towards commercial ....Translational Design: Product Development for Research Commercialisation. Australia is a world leader in fundamental research. Yet, ranks as one of the worst developed nations for translating research into new-to-market innovation. This project explores a new role for design as a critical component of research commercialisation and innovation ecosystems. It expects to contribute novel insights into how designers can be better integrated into interdisciplinary research directed towards commercial outcomes. Expected outcomes include a framework and toolkit for a paradigm-shifting design approach to translating fundamental research into products commercialised and manufactured in Australia. This should provide enhanced economic benefit, building Australia’s sovereign capability in new-to-market innovation.Read moreRead less
Using acoustic retroreflection in architecture to improve rooms for speech. This project aims to discover how a novel form of acoustic treatment can improve acoustics for speech in rooms such as classrooms and open-plan offices. The project will generate new knowledge on the theory, design, and effects of acoustically retroreflective surfaces in room acoustics. Expected outcomes include solutions for effective acoustic retroreflectors, knowledge on how retroreflection influences people’s voice r ....Using acoustic retroreflection in architecture to improve rooms for speech. This project aims to discover how a novel form of acoustic treatment can improve acoustics for speech in rooms such as classrooms and open-plan offices. The project will generate new knowledge on the theory, design, and effects of acoustically retroreflective surfaces in room acoustics. Expected outcomes include solutions for effective acoustic retroreflectors, knowledge on how retroreflection influences people’s voice regulation and sound quality perception, and guidelines and simulation tools for integrating retroreflective treatments to improve speaking comfort. This should provide significant benefits including opportunities to resolve seemingly intractable design dilemmas in the acoustics of education and workplace environments.Read moreRead less
Designing for wellbeing: realizing benefits for patients through best practice hospital design. The environmental design of healthcare facilities has been shown to directly affect the wellbeing of patients and their families. Poorly designed environments exacerbate patient anxiety and stress and diminish their healthcare experience. Environments designed to support a patient’s wellbeing result in improved health outcomes. Building upon Australia’s international leadership in contemporary hospita ....Designing for wellbeing: realizing benefits for patients through best practice hospital design. The environmental design of healthcare facilities has been shown to directly affect the wellbeing of patients and their families. Poorly designed environments exacerbate patient anxiety and stress and diminish their healthcare experience. Environments designed to support a patient’s wellbeing result in improved health outcomes. Building upon Australia’s international leadership in contemporary hospital design, this project aims to evaluate, prioritise and strategise the best means for realising benefits of environmental design factors that contribute most significantly to achieving positive outcomes for patients and families. It aims to achieve this through a comprehensive comparative case study analysis of new Australian paediatric hospitals.Read moreRead less
Digital fabrication technologies: analysing patterns of adoption and innovative transformations in architectural design and practice. This project on adoption of digital fabrication technologies by Australian architecture practices will reveal emerging opportunities for creative design and associated transformations in the design practices. These outcomes will enable the increasingly globalising sector of architectural design services to become more agile and innovative.
Place and parametricism: Provocations for the rethinking of design. This project aims to explore whether quantitative methods of digital and parametric design can adequately encompass place. Quantitative digital and parametric approaches increasingly dominate contemporary architecture, but people assume architectural design should be essentially oriented to questions of place. The project will operate through a set of studio provocations based on the fictional places of Mervyn Peake's Gormenghas ....Place and parametricism: Provocations for the rethinking of design. This project aims to explore whether quantitative methods of digital and parametric design can adequately encompass place. Quantitative digital and parametric approaches increasingly dominate contemporary architecture, but people assume architectural design should be essentially oriented to questions of place. The project will operate through a set of studio provocations based on the fictional places of Mervyn Peake's Gormenghast novels. The project is expected to clarify the nature of place and parametricism, and rethink what design itself might be.Read moreRead less