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
Understanding multiday cycles underpinning human physiology. We recently discovered long-term rhythms modulating activities of our brains and hearts ranging in duration from 3-60 days. The cause of these longer, ‘multiday cycles’ remain unknown. This project aims to understand; causes of multiday cycles (measuring the nervous and autonomic nervous system), their effects (on cognition, sleep, and stress), and quantify the relationship between coupled cyclical systems. The research outcomes can pr ....Understanding multiday cycles underpinning human physiology. We recently discovered long-term rhythms modulating activities of our brains and hearts ranging in duration from 3-60 days. The cause of these longer, ‘multiday cycles’ remain unknown. This project aims to understand; causes of multiday cycles (measuring the nervous and autonomic nervous system), their effects (on cognition, sleep, and stress), and quantify the relationship between coupled cyclical systems. The research outcomes can provide fundamental new knowledge about cyclic dynamics governing human physiology, leading to improved rigour in life sciences research. Commercial outcomes include technology to optimise individual productivity, learning, health, and wellbeing based on physiological cycles, with diverse benefits to society.Read moreRead less
INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generat ....INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generate synchronised neuronal activity. This project aims to investigate mechanisms underlying a specific class of brain rhythm implicated in control of mood states. Positive outcomes from this basic research may lead to better drug therapies for controlling specific mental disorders.Read moreRead less
Ultradian rhythms in basal metabolism; relationship to thermoregulation, cardiovascular function and behavioural arousal. Results from this project will be of basic theoretical biological importance, and may well provide a foundation for understanding basal metabolic regulation and its link with cardiovascular function. Our findings may provide a new foundation for discovering strategies that alter basal metabolic rate in a manner that improves health and reduces the incidence of obesity related ....Ultradian rhythms in basal metabolism; relationship to thermoregulation, cardiovascular function and behavioural arousal. Results from this project will be of basic theoretical biological importance, and may well provide a foundation for understanding basal metabolic regulation and its link with cardiovascular function. Our findings may provide a new foundation for discovering strategies that alter basal metabolic rate in a manner that improves health and reduces the incidence of obesity related disease such as heart attack and stroke. Thus this research proposal is of special relevance to National Research Priority 2: Promoting and Maintaining Good Health. Obesity and obesity-related medical conditions particularly affect older people, so that our research is also highly relevant to National Research Priority 2 sub-areas: Ageing well, Ageing productively.Read moreRead less
Neurological cell replacement therapies: improving outcomes by matching developmental profiles of transplanted cells with the damaged brain area. Stem cell transplantation offers a way to replace nerve cells lost due to acute CNS injury or chronic degenerative conditions such as Parkinson's Disease. However, to date, results have been disappointing because of poor differentiation, survival and integration of stem cells confounded by ethical issues associated with the use of embryos as the source ....Neurological cell replacement therapies: improving outcomes by matching developmental profiles of transplanted cells with the damaged brain area. Stem cell transplantation offers a way to replace nerve cells lost due to acute CNS injury or chronic degenerative conditions such as Parkinson's Disease. However, to date, results have been disappointing because of poor differentiation, survival and integration of stem cells confounded by ethical issues associated with the use of embryos as the source of stem cells. The experiments conducted in this study will provide strategies to improve the efficacy of stem cell transplantation into the damaged CNS as well as developing the use of autologous bone marrow stem cells for repair. Outcomes will be improved transplant methodologies and expertise for the bio-technology industry. Read moreRead less
Novel tractography-guided MRI methods for studying healthy brain ageing. Advances in imaging, and particularly Magnetic Resonance Imaging, have opened a new era in the study of the brain enabling a myriad of neuroscience discoveries. This project aims to develop new analysis methods to study and understand the variability in the human brain during ageing, exploiting the wealth of information contained in the so-called tractogram, a mapping of the brain’s wiring. This project expects to develop i ....Novel tractography-guided MRI methods for studying healthy brain ageing. Advances in imaging, and particularly Magnetic Resonance Imaging, have opened a new era in the study of the brain enabling a myriad of neuroscience discoveries. This project aims to develop new analysis methods to study and understand the variability in the human brain during ageing, exploiting the wealth of information contained in the so-called tractogram, a mapping of the brain’s wiring. This project expects to develop innovative imaging biomarkers to characterise the brain changes in the course of healthy brain ageing. Expected outcomes include novel imaging tools for neuroscience, which should allow us to map trajectories of normative healthy brain ageing and use them to identify lifestyle factors that impact these trajectories.Read moreRead less
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly inc ....Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly increase our understanding of how the development of this critical aspect of organismal function is orchestrated during development. This project will also develop bioinformatics tools with broad utility within the biosciences field and enhance the capacity for interdisciplinary international collaborations.Read moreRead less
Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated ....The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated appreciably in the past. We believe that these sensory neural circuits will reveal important new insights into how internal organs perform their diverse and essential functions to sustain life.Read moreRead less