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
Clarifying The Pathogenic Role Of Arousal-hyperventilation In Obstructive And Central Sleep Apnoea: Testing Fundamental Pathophysiological Mechanisms And A Strategic New Treatment
Funder
National Health and Medical Research Council
Funding Amount
$414,717.00
Summary
This project is designed to understand the mechanisms underpinning much more stable breathing during deep sleep in obstructive sleep apnoea (OSA). A newly developed analytical technique will be used to examine breathing effort changes across sleep, and interactions with respiratory-induced awakenings in OSA patients. In addition, a new treatment designed to stabilise breathing will be tested and refined towards a new treatment option for OSA and for central sleep apnoea.
The Role Of Arousal And Diaphragm Displacement In The Pathogenesis Of Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$410,875.00
Summary
Obstructive sleep apnea (OSA) affects 4% of men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease e.g. heart attacks and strokes. OSA is characterized by repetitive obstructions of the floppy portion of the throat during sleep with adverse effects on oxygen levels and sleep quality. OSA is strongly associated with obesity and is 2-3 times more common in men than women. How obesity and male gender predispose to OSA is ....Obstructive sleep apnea (OSA) affects 4% of men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease e.g. heart attacks and strokes. OSA is characterized by repetitive obstructions of the floppy portion of the throat during sleep with adverse effects on oxygen levels and sleep quality. OSA is strongly associated with obesity and is 2-3 times more common in men than women. How obesity and male gender predispose to OSA is not known. We will investigate two factors that we believe are most likely involved in causing and explaining this gender difference in OSA. We will examine if breathing responses with brief awakening are sufficient to promote OSA patterns of breathing in snorers and if they are greater in male than female OSA patients. We have already shown that healthy men have greater breathing response to arousal compared to women. These brief arousals occur hundreds of times a night in OSA patients, and over-breathing on arousal may increase the probability of upper airway obstruction on falling back to sleep. We will also investigate why even healthy men show greater breathing responses compared to women. Men tend to accumulate fat centrally, particularly in the abdomen, whereas in women fat tends to be distributed more to the hips and thighs. This could be very important in OSA because downward pull exerted on the upper airway by the diaphragm is likely to be reduced in people with more abdominal obesity. This mechanisms has not yet been studied in humans. We will therefore investigate if increased forces placed on the diaphragm during sleep make the upper airway more prone to collapse. We will also investigate these effects during sleep onset, when there may well be important changes in diaphragm position as muscles relax.Read moreRead less
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
The Role Of Adipokines In Modulation Of Gastric Vagal Afferent Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$624,535.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and may be influenced by factors released from fat stores in the body. The aim of this project is to determine how these factors interact with gastric nerve satiety signals and thus identify targets for the pharmacological treatment of obesity.
Ecology, morphology and the diversification of Australian lizards. This project aims to determine the factors driving the spectacular radiation of lizards in Australia. To date, most investigations of lizard anatomy have focused exclusively on external characteristics. This project will examine the underlying internal anatomy to investigate whether morphological innovation is associated with enhanced rates of ecological, life-history and species diversification. The project expects to shed light ....Ecology, morphology and the diversification of Australian lizards. This project aims to determine the factors driving the spectacular radiation of lizards in Australia. To date, most investigations of lizard anatomy have focused exclusively on external characteristics. This project will examine the underlying internal anatomy to investigate whether morphological innovation is associated with enhanced rates of ecological, life-history and species diversification. The project expects to shed light on the evolution of Australia’s most diverse vertebrate lineage, and provide comparative data with which to interpret the lizard fossil record in Australia, and the range declines and relative extinction risks of native lizard species.Read moreRead less
Identification Of Genes For X-linked Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$675,228.00
Summary
We propose to identify novel heritable causes of intellectual disability using 22 large and well-characterised families from Australia. In these families we have refined the location of the genetic defect to the chromosome X and excluded the contribution of all so far known genes. We will achieve this using the technology of massive parallel sequencing. At the completion of the project we will have identified novel causes of intellectual disability and devised tests to identify them.
The Aboriginal Cardiovascular Omega-3 Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,090,119.00
Summary
CVD is the primary contributor to life expectancy differentials between Indigenous and non-Indigenous Australians. Even when cardioprotective therapies are optimally used, residual risk of adverse events is often observed. Testing of additional therapies that improve survival among Indigenous people with CVD is required. Omega 3 fatty acids can improve multiple atherogenic pathways. This trial will assess the impact of Omega 3 in Aboriginal patients with CVD.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Male-female Sperm Signalling - A Novel Pathway For Peri-conceptual Health?
Funder
National Health and Medical Research Council
Funding Amount
$674,920.00
Summary
This project will investigate a new biological process in reproduction, whereby sperm delivered to the cervix at coitus transmit signalling molecules called microRNAs that influence the female immune response, to increase the chances of conception and pregnancy. We will define the molecular details of this signalling pathway in mouse models, and then determine whether human sperm have a comparable function in ‘priming’ the female body to conceive.