Hypoxia-induced Suppression Of Respiratory Sensations And Reflexes
Funder
National Health and Medical Research Council
Funding Amount
$276,750.00
Summary
Many diseases that effect the respiratory system have their primary effect on the lungs and airway themselves but in some conditions, such as obstructive sleep apnea (OSA) and asthma, increased breathing load can induce periods of low blood oxygen which could further contribute to morbidity in these diseases. OSA is a disorder associated with snoring. Patients experience periods of sleep fragmentation and oxygen deprivation due to obstruction of the floppy portion of the upper airway (pharynx) d ....Many diseases that effect the respiratory system have their primary effect on the lungs and airway themselves but in some conditions, such as obstructive sleep apnea (OSA) and asthma, increased breathing load can induce periods of low blood oxygen which could further contribute to morbidity in these diseases. OSA is a disorder associated with snoring. Patients experience periods of sleep fragmentation and oxygen deprivation due to obstruction of the floppy portion of the upper airway (pharynx) during sleep. It affects 4% of men and 2% of women and causes excessive daytime sleepiness leading to increased risk of accidents, high blood pressure and premature cardiovascular disease. Asthma produces airway inflamation and narrowing and affects a wide range of people. Both OSA and asthma are associated with episodes of impaired breathing and reduced levels of oxygen in the blood. Low levels of oxygen in the blood (hypoxia) is well known to impair functioning of the central nervous system. We have recently found that hypoxia blunts sensations of increased breathing load in healthy people and in asthmatics. Hypoxia might therefore contribute to worsening of attacks in these diseases. This study aims to investigate how changes in blood oxygen levels affect brain processing of respiratory signals, how this translates to perception of sensations and the physiological adaptations that people make to cope with increased breathing load. We will also investigate whether the inhibitory effects of hypoxia on central nervous system function extend to other vital protective respiratory reflexes such as cough, awakening from sleep to increased breathing load and upper airway reflexes that are important for maintaining an open airway.Read moreRead less
Role Of Zinc In The Respiratory Epithelium And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example ....This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example, asthma affects 12% of adults and amongst these, 15% waken weekly or more often with their asthma while 6% are hospitalized annually. There is a need to understand the basic mechanisms underlying these diseases so that new strategies can be developed to modify bronchocondtriction and inflammation. The project will provide new knowledge concerning the physiology of Zn in the respiratory epithelium and interactions between Zn deficiency and oxidants on injury in the respiratory tract. The usefulness of easily accessible nasal epithelial cells as a measure of Zn and Zn transporter levels deeper in the respiratory tract will be assessed. The project encompasses a number of fields and utilizes in vitro cellular and animal models, as well as tissues from human subjects.Read moreRead less
The biology and epidemiology of the grapevine canker fungi, Botryosphaeria sp. Decline and dieback of grapevines is becoming an increasing problem for the viticulture industry in NSW. Recently, species of the fungus Botryosphaeria, were isolated from grapevines exhibiting these symptoms. In order to understand the biology and epidemiology of the causal organisms, we aim to; (i) determine species of Botryosphaeria present in NSW vineyards; (ii) determine which species are pathogenic on grapevines ....The biology and epidemiology of the grapevine canker fungi, Botryosphaeria sp. Decline and dieback of grapevines is becoming an increasing problem for the viticulture industry in NSW. Recently, species of the fungus Botryosphaeria, were isolated from grapevines exhibiting these symptoms. In order to understand the biology and epidemiology of the causal organisms, we aim to; (i) determine species of Botryosphaeria present in NSW vineyards; (ii) determine which species are pathogenic on grapevines; (iii) characterise the genetic diversity of strains and; (iv) screen fungicides for the control of these fungi. Information on the species, their biology and pathogenicity on grapevines, will enable the development of appropriate management strategies for its control and may lead to the development of molecular tools to identify species of Botryosphaeria.Read moreRead less
Refining the timescale of human evolution and dispersal using ancient DNA. Understanding the timescale of human evolution and migration is a key goal of genetic analysis. It provides the foundation for studying our evolutionary and demographic history, our relationships to other hominids and our impact on the natural world. This project aims to use ancient DNA data to improve estimates of our evolutionary timescale.
Airway Epithelial IAPs And Their Interaction With Zn Ions
Funder
National Health and Medical Research Council
Funding Amount
$260,779.00
Summary
The air we breathe contains a variety of harmful substances. Damage to the lining involves death of the ciliated cells that line the airways. We have shown that zinc protects these cells from premature death. This application focuses on a family of proteins called IAPs which bind zinc and regulate cell death in other tissues. This project focusses on how the IAPs and Zn may act together to mainitain healthy airways and how abnormalities of these may occur in people with asthma.
Discovery Early Career Researcher Award - Grant ID: DE180100883
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Palaeo-population genomics: studying adaptation using ancient human DNA. This project aims to apply state-of-the-art population and quantitative genetic techniques to a powerful new database of ancient human genomes - spanning from hunter gatherers and early farmers through to the Middle Ages. This will be used to build the first detailed portrait of human genetic adaptation through time. This record will capture the major socio-cultural transitions in human history, and reveal the genetic and e ....Palaeo-population genomics: studying adaptation using ancient human DNA. This project aims to apply state-of-the-art population and quantitative genetic techniques to a powerful new database of ancient human genomes - spanning from hunter gatherers and early farmers through to the Middle Ages. This will be used to build the first detailed portrait of human genetic adaptation through time. This record will capture the major socio-cultural transitions in human history, and reveal the genetic and environmental drivers that have shaped modern human genetic diversity and pathology.Read moreRead less
Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the ....Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the controlled release of therapeutic compounds. The involvement of Honours and Ph.D students in this project will expose the next generation of Australian scientists to this emerging discipline. International collaboration leading to publications in high impact scientific journals will enhance Australia's scientific reputation.Read moreRead less
Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essenti ....Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essential target genes that drive lymphatic development. The project expects to generate fundamental knowledge in vascular signalling, transcription and the control of vascular network growth and expansion. Outcomes may provide significant benefits in new approaches in stem cell biology, tissue engineering and regenerative biology. Read moreRead less
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.