The development and testing of a device to enhance the application of repetitive transcranial magnetic stimulation. This project aims to develop and evaluate a new device designed to substantially enhance the use of transcranial magnetic stimulation, a technology, which is increasingly being applied in the treatment of disorders such as depression, as well as in the study of normal and abnormal brain function.
Modelling the human nervous system with human pluripotent stem cells. The human nervous system is one of the most complex structures evolved to date. In order to understand how it functions, and dysfunctions in a diseased state, it is fundamental to decipher how it develops to generate various neuronal populations that form this elaborate network. Human stem cells provide a valuable source to study such processes. The aim of this project is to use human stem cells to study how early progenitor c ....Modelling the human nervous system with human pluripotent stem cells. The human nervous system is one of the most complex structures evolved to date. In order to understand how it functions, and dysfunctions in a diseased state, it is fundamental to decipher how it develops to generate various neuronal populations that form this elaborate network. Human stem cells provide a valuable source to study such processes. The aim of this project is to use human stem cells to study how early progenitor cell types that structure the nervous system are generated and how their neuronal derivatives form connectivity and functional synapses. The outcome of these studies is that we will establish a cellular model of human neurogenesis that can be utilised to study developmental disease processes.Read moreRead less
Biophysics-informed deep learning framework for magnetic resonance imaging. This project aims to bring about a paradigm shift from the conventional non-quantitative magnetic resonance imaging to ultra-fast, quantitative, and artefact free imaging. This project integrates biophysics and artificial intelligence, and it is expected to bring new knowledge in both fields. The expected outcomes of this project include next generation magnetic resonance imaging methods with a fundamental shift in the ....Biophysics-informed deep learning framework for magnetic resonance imaging. This project aims to bring about a paradigm shift from the conventional non-quantitative magnetic resonance imaging to ultra-fast, quantitative, and artefact free imaging. This project integrates biophysics and artificial intelligence, and it is expected to bring new knowledge in both fields. The expected outcomes of this project include next generation magnetic resonance imaging methods with a fundamental shift in the approach to image artefacts and image quantification. This project is expected to advance both single subject and population level biomedical imaging with greater accuracy and cost-effectiveness. This project also promotes explainable and generalisable artificial intelligence in medical imaging.Read moreRead less
Investigating the intercellular trafficking of proteins and RNA and its relevance to neurodegenerative diseases. Alzheimer's and prion diseases are neurodegenerative disorders associated with protein misfolding. This project brings together similar features of these diseases using novel cell- and animal-based studies to develop a greater understanding of the molecular basis of these disorders.
Towards direct imaging of neuronal currents with MRI. This project aims to develop novel neuronal current magnetic resonance imaging (nc-MRI) methods that harness the oscillatory behaviour of neuronal magnetic fields. Current methods of detecting neuronal activity in the living human brain have limited spatial and temporal resolution. Use of nc-MRI aims to overcome these limitations by imaging the effects on the MRI signal of small transient magnetic fields associated with neuronal activity. Sig ....Towards direct imaging of neuronal currents with MRI. This project aims to develop novel neuronal current magnetic resonance imaging (nc-MRI) methods that harness the oscillatory behaviour of neuronal magnetic fields. Current methods of detecting neuronal activity in the living human brain have limited spatial and temporal resolution. Use of nc-MRI aims to overcome these limitations by imaging the effects on the MRI signal of small transient magnetic fields associated with neuronal activity. Signal-to-noise ratio is at the limits of detectability using current imaging systems and nc-MRI is yet to be convincingly demonstrated. An integrated framework for simulating nc-MRI in the visual cortex is expected to be developed.Read moreRead less
The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will presen ....The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will present a medical and economic challenge demanding novel and powerful science. This research will lead both to deeper understanding of the basic mechanisms underlying such disorders and to tools for designing new and effective treatments.
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The Role Of Netrin-DCC In The Development Of The Corpus Callosum
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with ove ....During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with over 50 different human congenital syndromes. Thus understanding how the genes and molecules involved in the formation of the corpus callosum function in normal development can provide the basis for our understanding of what goes wrong in ACC. In this proposal we will investigate the role of the axon guidance molecule Netrin1, and its receptor DCC, in development of the corpus callosum in both a mouse model and in humans with malformations of the corpus callosum. Although Netrin1-DCC signalling has traditionally been associated with mechanisms of axon guidance, we hypothesize that these molecules may play a different role, specifically in cellular adhesion and ultimately in the fusion of the two cerebral hemispheres, in a manner that allows the corpus callosum to form. A second role for Netrin1-DCC signalling may be in the guidance of these axons once the midline has fused correctly and we investigate this in Aim 2 of the proposal. Finally, we are collaborating with a paediatric neurologist at UCSF, who has identified several mutations in the DCC gene in patients with ACC. In Aim 3 we test whether these mutations disrupt the function of DCC in callosal axon pathfinding. Understanding how these genes function during development of the brain and how their function may be altered in ACC is crucial to providing a proper diagnosis and prognosis for these patients. Ultimately, understanding more about how these genes function could also lead to prevention of these disorders.Read moreRead less
Integrative brain imaging technologies. This project aims to develop quantitative metabolic imaging using simultaneous magnetic resonance imaging (MRI) and positron emission tomography (PET). The current generation of MR-PET scanners are capable of simultaneously acquiring MRI and PET data to enable quantitative anatomical, physiological and metabolic imaging. The project aims to develop new MRI methods for quantitative anatomical mapping, MR-based motion correction of dynamic PET scan data, and ....Integrative brain imaging technologies. This project aims to develop quantitative metabolic imaging using simultaneous magnetic resonance imaging (MRI) and positron emission tomography (PET). The current generation of MR-PET scanners are capable of simultaneously acquiring MRI and PET data to enable quantitative anatomical, physiological and metabolic imaging. The project aims to develop new MRI methods for quantitative anatomical mapping, MR-based motion correction of dynamic PET scan data, and joint estimation of physiological and metabolic organ activity. These advances will create innovative imaging technologies for advanced biomedical imaging research with a particular emphasis in healthy ageing.
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Genetic dissection of functional-structural connectivity using optogenetic fMRI and dMRI tractography. The project will map the connectivity pattern of genetically defined neurons in mouse brain by combining state of the art molecular and neuroscience imaging technology. The outcome will be a significant step toward building a complete functional and structural mapping resource, with application for examining dysfunction in neurological disease models.