Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
In-vivo detection of airway injury and disease using phase contrast X-ray velocimetry. Currently diagnosis of lung disease, a major cause of death in humans, is based on clinical symptoms that do not usually manifest until the disease is well advanced. This project will develop a novel imaging technique, X-ray velocimetry, to detect changes in tissue before symptoms arise, potentially leading to strategies for managing lung diseases.
Low dose methods for detecting early lung disease using x-ray phase contrast imaging. This project will develop a highly sensitive, low-dose x-ray imaging technique for the early detection of diseases of the respiratory system. This technology will have the potential to be used as a diagnostic screening tool to reduce the incidence of respiratory related deaths from diseases such as lung cancer and emphysema.
Advanced imaging technology for measuring pulmonary form and function. Studies of the lung are often limited by difficulties associated with imaging the complex network of airways with conventional techniques. This project will develop novel phase contrast image x-ray imaging technologies to enable quantitative measurements of lung structure and function for studying lung development and assessing lung health.
Common synaptic inputs to human upper airway muscles. Changes in the activity of upper airway muscles at sleep onset contribute to the development of Obstructive Sleep Apnoea. The aim of this project is to investigate how the brain controls upper airway muscles during wakefulness and sleep and to identify the pathological processes that lead to the development of Obstructive Sleep Apnoea.
Age and Gender Related Changes in Motor Control of the Upper Airway Muscle Genioglossus During Sleep. Obstructive Sleep Apnoea (OSA) is the repetitive obstruction of the airway during sleep. Obstructions occur because muscles of the upper airway fail to keep the airway open during inspiration. The disorder is associated with cardiovascular disease and cognitive and behavioural impairment. The prevalence of the disorder increases in older adults, contributing to age-related health and behavioural ....Age and Gender Related Changes in Motor Control of the Upper Airway Muscle Genioglossus During Sleep. Obstructive Sleep Apnoea (OSA) is the repetitive obstruction of the airway during sleep. Obstructions occur because muscles of the upper airway fail to keep the airway open during inspiration. The disorder is associated with cardiovascular disease and cognitive and behavioural impairment. The prevalence of the disorder increases in older adults, contributing to age-related health and behavioural problems. However, age-related changes differ in men and women. We believe the high prevalence of OSA in older adults is due to age and gender related changes in the activity of muscles in the upper airway. We will study the behaviour of the upper airway muscle genioglossus during sleep in young, middle-aged and older men and women.Read moreRead less
Phase Contrast X-ray Imaging of the Lung. Lung diseases are a major cause of death in adults, children and newborn infants. Currently, the diagnosis of lung disease is based on clinical symptoms, which usually do not manifest until the disease is well advanced. This project will develop a novel X-ray imaging technique, known as phase contrast imaging, to study the lung, and to potentially detect changes in lung tissue before symptoms arise. This may lead to improved strategies for managing newbo ....Phase Contrast X-ray Imaging of the Lung. Lung diseases are a major cause of death in adults, children and newborn infants. Currently, the diagnosis of lung disease is based on clinical symptoms, which usually do not manifest until the disease is well advanced. This project will develop a novel X-ray imaging technique, known as phase contrast imaging, to study the lung, and to potentially detect changes in lung tissue before symptoms arise. This may lead to improved strategies for managing newborn infants, as well as improving the management of lung diseases in adults.Read moreRead less
Cardiovascular and Respiratory Activity During Sleep Onset. Going to sleep requires that behavioural and physiological activities be modified. This is achieved by the integrated activity of sleep mechanisms and the circadian system. In this project we will investigate the nature of the regulatory control exerted by sleep mechanisms over respiration and cardiovascular activity at sleep onset, how sleep control interacts with circadian influence, and the nature of cardio-respiratory activity when ....Cardiovascular and Respiratory Activity During Sleep Onset. Going to sleep requires that behavioural and physiological activities be modified. This is achieved by the integrated activity of sleep mechanisms and the circadian system. In this project we will investigate the nature of the regulatory control exerted by sleep mechanisms over respiration and cardiovascular activity at sleep onset, how sleep control interacts with circadian influence, and the nature of cardio-respiratory activity when sleep control is removed at an arousal from sleep. It is anticipated that a better understanding of the regulatory control exerted by sleep over other systems will improve our understanding of sleep disorders.Read moreRead less
Engineering an environmentally-friendly metered dose inhaler. This project aims to deliver a novel simulation framework to accurately predict the behaviour of metered dose inhaler sprays using advanced numerical methods for flash-evaporating turbulent flows developed by the investigators. The project expects to generate new knowledge of the complex physics which occur in these devices through a first of its kind combination of unsteady non-equilibrium thermodynamics, turbulence and spray models. ....Engineering an environmentally-friendly metered dose inhaler. This project aims to deliver a novel simulation framework to accurately predict the behaviour of metered dose inhaler sprays using advanced numerical methods for flash-evaporating turbulent flows developed by the investigators. The project expects to generate new knowledge of the complex physics which occur in these devices through a first of its kind combination of unsteady non-equilibrium thermodynamics, turbulence and spray models. Expected outcomes of this project include a novel ability to predict and optimise the performance of inhalers to suit environmentally-friendly replacement propellants. This will significantly benefit the pharmaceutical sector as it will accelerate the design of next-generation inhalers and propellants.Read moreRead less
Respiratory and Cardiovascular Activation at Arousal from Sleep. An arousal from sleep, no matter how brief, is assciated with increased activity in the respiratory and cardiac systems. Under normal circumstances the response is considered adaptive. However, in disorders of sleep in which individuals arouse frequently and their sleep is fragmented, such as in Obstructive Sleep Apnea, the phenomenon has been linked to hypertension. While the clinical consequences of sleep fragmentation are now ap ....Respiratory and Cardiovascular Activation at Arousal from Sleep. An arousal from sleep, no matter how brief, is assciated with increased activity in the respiratory and cardiac systems. Under normal circumstances the response is considered adaptive. However, in disorders of sleep in which individuals arouse frequently and their sleep is fragmented, such as in Obstructive Sleep Apnea, the phenomenon has been linked to hypertension. While the clinical consequences of sleep fragmentation are now apparent, the mechanism that causes the increase in physiological activity at each arousal, is not known. The aim of this project will provide insight into the mechanism that produces the activation response and provide a basis for minimising the cardiac consequences of sleep disorders.Read moreRead less