Ontogeny Of The Airway Smooth Muscle Layer In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$535,914.00
Summary
In asthmatic patients the thickness of the airway smooth muscle (ASM) layer is increased early in life and even before doctor-diagnosis. An intriguing possibility is our overarching hypothesis that the ASM layer is thickened from birth and represents an independent risk factor for the development of asthma. This project strives to understand better how the ASM layer matures from late gestation to adulthood and whether abnormal maturation contributes to disease susceptibility.
Exploring The Therapeutic Potential Of TRAIL In Diabetes And The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$446,374.00
Summary
TNF-related apoptosis-inducing ligand (TRAIL) is a protein with potentially useful actions in human health and disease. TRAIL is able to prevent atherosclerosis, the cause of heart attacks and strokes. In addition, we have recently shown that its actions on fat and the pancreas may prevent the development of the metabolic syndrome and type 2 diabetes. These studies will explore the therapeutic potential of TRAIL for the prevention of diabetes and heart disease in a range of animal models.
Failure-to-progress In Human Labour Results From A Profound Electrical Negativity Of The Uterine Cells: Targeting The Ion Channels Involved
Funder
National Health and Medical Research Council
Funding Amount
$564,541.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems to lay the foundations for better therapeutics.
Increased Airway Smooth Muscle Mass As An Independent Determinant Of Asthma Pathogenesis And Severity
Funder
National Health and Medical Research Council
Funding Amount
$409,966.00
Summary
Asthma is a major health burden to the community. The most common form of the disease is allergic asthma and it is thought that allergic inflammation drives associated airway abnormalities including increased airway smooth muscle (ASM) mass. This study tests a new hypothesis that airway abnormalities and allergy have separate origins but combine to produce allergic asthma, and it’s the individuals with the greatest amount of ASM who develop clinically severe asthma.
Heterogeneity Of Airway Smooth Muscle Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$623,078.00
Summary
Increased smooth muscle in the airways causes excessive narrowing and asthma symptoms. The distribution of the increased muscle in the lung varies between people with asthma and may determine how severe the asthma is and what treatments are best. This project will use tissues from many cases of asthma to map this distribution and will use laser scanning in the airways to develop a test to safely examine the smooth muscle in living people, in order to better treat or prevent asthma.
The Role Of The MicroRNA Let 7 In Diabetic Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$674,084.00
Summary
Cardiovascular complications remain the major cause of mortality in diabetes and our current treatment strategies are insufficient to reduce this burden. We have obtained extensive data to show that a novel molecule (the micro RNA, let 7b) has antiproliferative and vasculoprotective effects in diabetes. Thus, we propose that modulation of micro RNA let 7b specifically in vascular smooth muscle cells within the vascular wall represents a promising target to combat cardiovascular disease, in parti ....Cardiovascular complications remain the major cause of mortality in diabetes and our current treatment strategies are insufficient to reduce this burden. We have obtained extensive data to show that a novel molecule (the micro RNA, let 7b) has antiproliferative and vasculoprotective effects in diabetes. Thus, we propose that modulation of micro RNA let 7b specifically in vascular smooth muscle cells within the vascular wall represents a promising target to combat cardiovascular disease, in particular in diabetes.Read moreRead less
RZR-alpha In The Control Of Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$521,706.00
Summary
Four million Australians have cardiovascular disease accounting for 35% of all deaths. CVD is the most expensive disease burden and a National Health Priority. Smooth muscle cell growth is a cause of CVD. However, the mechanisms controlling SMC hyperplasia are poorly understood. This project will provide key insights on the role of RZR-alpha in the pathogenesis of blood vessel disease, and develop novel gene-targeting approaches for new opportunities to control complications of CVD.
Airway Smooth Muscle And Fixed Airway Obstruction: Strategies For Softening Muscle
Funder
National Health and Medical Research Council
Funding Amount
$555,643.00
Summary
In severe asthma the airways don't relax fully making breathing more difficult. The inability to relax is being addressed by exploring the behaviour of isolated muscle cells. These cells are able to compact collagen gels. The mechanisms used to compact the gel are different to those that cause rapid muscular contraction. We aim to identify the molecules responsible for the gel compaction as a first step to identifying new drugs to treat the fixed airway obstruction in severe asthma.
Understanding Uterine Contractility: What Can We Learn From Obesity?
Funder
National Health and Medical Research Council
Funding Amount
$600,792.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified five dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems, particularly those mechanisms in common.
Airway Extracellular Matrix And Smooth Muscle In Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$828,849.00
Summary
In asthma the layer of airway smooth muscle is thicker, due to more muscle cells. Airway narrowing is excessive but reversible. In chronic obstructive pulmonary disease (due mainly to smoking) the layer of airway smooth muscle is also thicker but the airways cannot be induced to open, or close. Our data suggest that this fixed airway narrowing is likely to be due to an excess of matrix between cells rather than muscle. This project will comprehensively test this new finding.