Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and r ....Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and research skill base. Young scientists will be trained in state-of-the-art research techniques in a cross-disciplinary environment that is the way of future biological research. The project may identify potential drug targets for malaria or other infectious diseases. The Intellectual Property will be protected and commercialised.Read moreRead less
Simultaneous measurement of brain function and behaviour in fully conscious laboratory animals. MicroPET is an advanced imaging technology that measures important biochemical processes, such as enzyme activity rates and receptor binding, in the living rodent brain. However, the requirement for the animal to be anaesthetised precludes the study of behavioural changes in response to sensory or drug stimulus during the imaging study. In this research, we will develop novel motion tracking and compu ....Simultaneous measurement of brain function and behaviour in fully conscious laboratory animals. MicroPET is an advanced imaging technology that measures important biochemical processes, such as enzyme activity rates and receptor binding, in the living rodent brain. However, the requirement for the animal to be anaesthetised precludes the study of behavioural changes in response to sensory or drug stimulus during the imaging study. In this research, we will develop novel motion tracking and computational algorithms that enable microPET to non-invasively image the brains of conscious, freely moving animals while simultaneously observing their behaviour. These new technologies will, for the first time, allow neuroscientists to study the genetic, behavioural and neurochemical correlates of brain disease.Read moreRead less
The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Gene therapy to enhance auditory prosthesis performance for cochlear implants. The cochlear implant is the most effective neural prosthesis, restoring hearing to the deaf. The research aims to develop a new type of implant compatible with delivery of therapeutic genes to the cells lining the cochlea. Gene therapy DNA constructs will be developed that will enhance neural survival and growth, improving cochlear implant performance. The research will provide advances in understanding how to tran ....Gene therapy to enhance auditory prosthesis performance for cochlear implants. The cochlear implant is the most effective neural prosthesis, restoring hearing to the deaf. The research aims to develop a new type of implant compatible with delivery of therapeutic genes to the cells lining the cochlea. Gene therapy DNA constructs will be developed that will enhance neural survival and growth, improving cochlear implant performance. The research will provide advances in understanding how to transfer genes into cochlear tissue, as well as development of gene cassettes for effective neural repair. The work will advance the field of bionics, an area where Australia is establishing international preeminence.Read moreRead less
Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453630
Funder
Australian Research Council
Funding Amount
$274,692.00
Summary
High-Speed Confocal Microscope Live Cell Recording System. The high-speed confocal microscope live cell recording system we are establishing represents new generation equipment. It allows quality imaging of selected subcellular regions of live cells combined with simultaneous electrophysiological recording at rates and sensitivity hitherto not possible. This equipment provides a window of opportunity for major research advances in that it allows real-time two and three-dimensional imaging of fun ....High-Speed Confocal Microscope Live Cell Recording System. The high-speed confocal microscope live cell recording system we are establishing represents new generation equipment. It allows quality imaging of selected subcellular regions of live cells combined with simultaneous electrophysiological recording at rates and sensitivity hitherto not possible. This equipment provides a window of opportunity for major research advances in that it allows real-time two and three-dimensional imaging of fundamental cellular activities that previously could not be viewed. It will allow major advances in priority health-related research and will provide an ideal research tool to introduce young scientists and students to cutting edge research.Read moreRead less
Targeting brain lipid homeostasis to treat Alzheimer's disease. Dementia affects approximately 250,000 people in Australia at an estimated cost (in 2002) of $6.6 billion per annum. The major cause of dementia (accounting for approximately 70% of all cases) is Alzheimer's disease (AD); a progressive neurodegenerative illness for which there is no curative or disease-stalling treatment. Due to increases in life expectancy, the incidence of AD is predicted to triple by 2050 unless disease-modifying ....Targeting brain lipid homeostasis to treat Alzheimer's disease. Dementia affects approximately 250,000 people in Australia at an estimated cost (in 2002) of $6.6 billion per annum. The major cause of dementia (accounting for approximately 70% of all cases) is Alzheimer's disease (AD); a progressive neurodegenerative illness for which there is no curative or disease-stalling treatment. Due to increases in life expectancy, the incidence of AD is predicted to triple by 2050 unless disease-modifying treatments are developed. This research program will provide novel realistic pharmaceutical approaches to treat AD. Even if the onset of AD could be delayed by a few years the personal and financial benefits would be enormous. The potential for this research to generate commercially viable Australian intellectual property is also significant.Read moreRead less
New Imaging Agents for Neuronal Nicotinic Receptors. Recent advances in medical imaging technology such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) have radically improved the diagnosis and treatment of a wide range of diseases. The aim of this project is to discover novel radio-ligands that selectively bind to neuronal nicotinic acetylcholine receptors. These ligands will have great potential for the imaging, diagnosis and study of neurodegenerat ....New Imaging Agents for Neuronal Nicotinic Receptors. Recent advances in medical imaging technology such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) have radically improved the diagnosis and treatment of a wide range of diseases. The aim of this project is to discover novel radio-ligands that selectively bind to neuronal nicotinic acetylcholine receptors. These ligands will have great potential for the imaging, diagnosis and study of neurodegenerative diseases such as Alzheimer's disease. Read moreRead less
Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a gr ....Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Non-invasive measurement of intracranial pressure by means of transcranial doppler blood flow and central aortic pressure. The investigation will produce a device that will aid doctors measuring brain pressure without drilling holes through the skull. The device will use the technology of an Australian company that has the only patented system to deduce the pressure in the brain by measuring pressure close to the heart and the brain and by recording the pressure pulse wave at the wrist. The comm ....Non-invasive measurement of intracranial pressure by means of transcranial doppler blood flow and central aortic pressure. The investigation will produce a device that will aid doctors measuring brain pressure without drilling holes through the skull. The device will use the technology of an Australian company that has the only patented system to deduce the pressure in the brain by measuring pressure close to the heart and the brain and by recording the pressure pulse wave at the wrist. The community benefit will be in terms of the safety and ease with which changes in pressure in the brain can be detected. It will also advance the world renowned Australian technology in a new area of application.Read moreRead less