The Role Of Arousal And Respiratory Control Factors In The Pathogenesis Of Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$567,924.00
Summary
Sleep apnoea (OSA) is a very common breathing disorder in sleep characterized by repetitive closure of the collapsible portion of the throat with serious effects on sleep quality and health. Basic causes of OSA are still largely unknown. We will investigate waking responses to breathing load and related respiratory control factors that we believe may be fundamental causes of OSA, and potentially explain many features of OSA including worsening in light sleep and with increasing age.
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
Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing seque ....Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing sequences and genes in microchromosomes of birds, reptiles and monotremes. This will clarify the origin and evolution of the ?microgenome?, establish its suitability as a model for vertebrate genome organisation, and demonstrate whether microchromosomes are the ancestors of the gene-rich regions of mammalian chromosomes.Read moreRead less
Radiostereometric Analysis Of The Effect Of A Large Articulation On Prosthetic Wear And Migration After Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$192,186.00
Summary
At total hip replacement, there has been a recent trend to use prostheses with a larger ball and liner in the socket. This may decrease the risk of post-operative dislocation, but may also increase the amount of wear, leading to bone loss and loosening of prostheses, which may then require replacement. This project will use a special type of x-ray to determine whether wear and movement of these new prostheses is clinically acceptable, so that they can be used with confidence in patients.
The Role Of Respiratory And Upper Airway Neural Control In Sleep Disordered Breathing
Funder
National Health and Medical Research Council
Funding Amount
$346,018.00
Summary
Obstructive Sleep Apnea (OSA) is a disorder associated with snoring. It affects 4% of adult men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease eg. heart attacks and strokes. Patients with OSA obstruct the floppy portion of the upper airway (UA) during sleep and consequently experience frequent episodes of oxygen deprivation as well as sleep fragmentation. OSA is at least 2-3 times more common in men than women. Whi ....Obstructive Sleep Apnea (OSA) is a disorder associated with snoring. It affects 4% of adult men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease eg. heart attacks and strokes. Patients with OSA obstruct the floppy portion of the upper airway (UA) during sleep and consequently experience frequent episodes of oxygen deprivation as well as sleep fragmentation. OSA is at least 2-3 times more common in men than women. While OSA patients seem, on average, to have smaller upper airways than normal subjects, the cause of OSA cannot be attributed to this factor alone. For example, a small UA cannot explain the male tendency for OSA. Abnormalities in breathing control or the control of upper airway muscles that normally hold the airway open might also be important in OSA. Men have previously been shown to have a greater increase in UA resistance during sleep than women, consistent with the idea that a gender difference in UA muscle control partly explains why more men than women have OSA. We aim to investigate how changes in breathing and UA dilator muscle control might lead to unstable patterns of breathing and to OSA. We propose that protective UA muscle reflexes are reduced during sleep more in men than women, and are reduced by low blood oxygen levels and alcohol (a known aggravator of sleep apnea). We further propose that low blood oxygen levels not only result from OSA but may also aggravate OSA by preferentially reducing the activity of UA dilating muscles, by making breathing patterns overall less stable and by depressing the ability of subjects to arouse from sleep to an airway blockage. We believe that this tendency to decrease UA activity may be exaggerated in OSA patients. We also propose that men are more vulnerable to the deleterious effects of low oxygen than women. We will also examine if men and snorers have exaggerated breathing responses on arousal from sleep.Read moreRead less
Road rules for traffic on DNA - gene regulation by encounters between transcribing RNA polymerases and DNA-bound proteins. This project addresses a widespread but poorly understood phenomenon in gene regulation. The work will support Australian industries by supplying new tools for manipulation of gene expression for industrial and medical applications and will provide unique opportunities for Australian students in this emerging field.
Non-coding RNAs in mammalian reproduction. This project aims to investigate the role of non-coding RNAs in mammalian sex chromosome biology and reproduction. Non-protein coding RNAs are a major regulatory mechanism in eukaryotic genomes; they can bind other RNAs or chromatin modifying complexes. However, the evolutionary trajectory and function of non-coding RNAs in sex chromosome biology and sexual development is largely unknown. This project will study non-coding RNAs in Australian mammals to ....Non-coding RNAs in mammalian reproduction. This project aims to investigate the role of non-coding RNAs in mammalian sex chromosome biology and reproduction. Non-protein coding RNAs are a major regulatory mechanism in eukaryotic genomes; they can bind other RNAs or chromatin modifying complexes. However, the evolutionary trajectory and function of non-coding RNAs in sex chromosome biology and sexual development is largely unknown. This project will study non-coding RNAs in Australian mammals to try to answer fundamental questions about how non-coding RNAs function in mammalian sexual development.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775503
Funder
Australian Research Council
Funding Amount
$255,000.00
Summary
Robotics for plant genomics: Increasing throughput in plant genetic analyses. Plant genomics has direct benefit to crop improvement, especially as focussed in the applicants' laboratories. Thus, the Australian agri-food sector will benefit substantially from the acceleration in plant functional genomics that will arise from the installation of the robotics equipment described in the current application, by both underpinning more applied research and also being used directly in crop improvement p ....Robotics for plant genomics: Increasing throughput in plant genetic analyses. Plant genomics has direct benefit to crop improvement, especially as focussed in the applicants' laboratories. Thus, the Australian agri-food sector will benefit substantially from the acceleration in plant functional genomics that will arise from the installation of the robotics equipment described in the current application, by both underpinning more applied research and also being used directly in crop improvement programs such as are based at the Waite Campus. The outputs will include crops with increased tolerance to biotic and abiotic stresses, a reduced dependence on chemical inputs such as fertilisers and improved food quality, with consequent benefits to the environment and human health and nutrition.Read moreRead less
Endosymbiotic DNA transfer. Interorganellar DNA movement is a major force in evolution. In higher organisms, the prokaryotic ancestors of mitochondria and chloroplasts donated many genes to the nucleus. Plants have unique potential in studies of the mechanisms that have driven genome evolution. We established experimentally that DNA moves from the chloroplast to the nucleus at high frequency and this provided us with a world lead in this scientifically new area. The relocated genes contribute to ....Endosymbiotic DNA transfer. Interorganellar DNA movement is a major force in evolution. In higher organisms, the prokaryotic ancestors of mitochondria and chloroplasts donated many genes to the nucleus. Plants have unique potential in studies of the mechanisms that have driven genome evolution. We established experimentally that DNA moves from the chloroplast to the nucleus at high frequency and this provided us with a world lead in this scientifically new area. The relocated genes contribute to the number and diversity of genes and gene function. Genetically manipulated (GM) crops use the chloroplast compartment to make high levels of protein, necessitating a full understanding of how transgenes behave within the cellular and the external environment.Read moreRead less