Is Lyn Tyrosine Kinase A Predictor Of Severe, Persistent Multi-trait Asthma And Allergy?
Funder
National Health and Medical Research Council
Funding Amount
$250,250.00
Summary
Asthma is a major health problem in Australia affecting over 10% of the population at any time, and more than 25% of the population at one stage in their lives. Although the public perception is that asthma treatments have improved management of the disease, more than 700 people die from severe asthma each year and hospitalisation from exacerbation (sudden worsening) is one of the most costly components of the health care burden in Australia and most developed countries. Currently there are no m ....Asthma is a major health problem in Australia affecting over 10% of the population at any time, and more than 25% of the population at one stage in their lives. Although the public perception is that asthma treatments have improved management of the disease, more than 700 people die from severe asthma each year and hospitalisation from exacerbation (sudden worsening) is one of the most costly components of the health care burden in Australia and most developed countries. Currently there are no molecular markers that can predict who will get severe asthma and there are no specific treatments to reverse severe exacerbations. This project will use advanced molecular biology methods to examine whether a molecule called Lyn may be important. The Lyn tyrosine kinase is a member of a family of genes that participate in transmitting information across the cell membrane. This enzyme is expressed in blood cells, and is involved in mechanisms pertaining to infection, immunity and allergic responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated mice that are unable to make Lyn protein (Lyn-deficient mice). In animal models of asthma we know that if Lyn is not functioning, severe and persistent asthma develops. We have also made preliminary studies that suggest that Lyn does not work properly in people who have been admitted to the emergency ward with life threatenting asthma. In this study we will examine in detail the role that Lyn plays in asthma and allergy, and we intend to identify the pathways that give rise to asthma in Lyn-deficient mice. We will also investigate our hypothesis that Lyn activity may be reduced or disregulated in patients with asthma and allergy. This research should lead to better predictive markers for severe asthma and also to improved and specific treatments.Read moreRead less
The Role Of Pulmonary Macrophages In The Pathogenesis Of An Acute Exacerbation Of Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$495,710.00
Summary
We will examine the role of lung defence cells, known as macrophages, in triggering the inflammation of acute severe asthma. The experimental work will use unique mouse models of mild chronic asthma and of an acute exacerbation of the illness, which have been developed in our laboratories. We will study the mechanisms of activation of the asthmatic response and assess whether treatment with drugs that suppress the function of macrophages can help to control steroid-resistant exacerbations.
Severe Malaria In Children In Papua New Guinea: A Longitudinal Study Of Pathophysiology, Management And Outcome
Funder
National Health and Medical Research Council
Funding Amount
$484,808.00
Summary
The features of severe infection in children living in tropical countries may not allow differentiation between malaria and bacterial-viral causes. This can create significant problems with deciding on appropriate management. In addition, the main complications of malaria such as coma, increased acid levels in the blood and anaemia are not well understood. We plan to characterise infections in Papua New Guinean children in detail and explore mechanisms behind important malarial complications.
Determinants Of Cytomegalovirus Salivary Gland Persistence
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Human cytomegalovirus (HCMV) persists for extended periods in the salivary gland, an organ of viral transmission. It is not clear how the virus avoids immune mediated control in this tissue. This aspect of viral pathology will be assessed in a mouse model using two strains of murine CMV which exhibit marked differences in salivary gland persistence. The role of tissue tropism (inhibition of apoptosis), viral immune evasion and host immunity in salivary gland persistence will be studied.
Macrophages, Sugars And Innate Immunity In Chronic Lung Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$413,150.00
Summary
This project is about a new idea to treat severe asthma, chronic obstructive lung disease (COPD) and sudden worsening of these diseases (exacerbations). Asthma and COPD are very common. Asthma afflicts approximately 10 % of all Australians and kills approximately 700 annually. COPD will be the third most common cause of death worldwide by 2010 (WHO) and costs more that $ AUS 10 Billion annually. The highest risk of death and greatest costs are associated with severe asthma and exacerbations. Our ....This project is about a new idea to treat severe asthma, chronic obstructive lung disease (COPD) and sudden worsening of these diseases (exacerbations). Asthma and COPD are very common. Asthma afflicts approximately 10 % of all Australians and kills approximately 700 annually. COPD will be the third most common cause of death worldwide by 2010 (WHO) and costs more that $ AUS 10 Billion annually. The highest risk of death and greatest costs are associated with severe asthma and exacerbations. Our idea, which is based on extensive animal data, is that these diseases can be treated by blocking the activity of proteins that allow a cell called the lung macrophage to grow, become activated, proliferate and survive. These proteins are called CSF-1 and GM-CSF and they belong to a larger class of proteins called colony stimulating factors (CSFs) Macrophages are important because they can rapidly respond to bacteria, viruses and fungi that can infect the lungs of asthma and COPD patients. Infections cause exacerbations. Normally, macrophages release a number of molecules called mediators that rouse a strong defensive reaction- a process called innate immunity. For example macrophages signal for a cell type called the neutrophil, which is a very efficient bacteria killer, to flood into the lung. However, these same cells can cause serious lung damage if the response is too strong or persistent. Macrophages and neutrophils need CSFs to work properly so blocking CSFs prevents lung damage. Although we now already know that blocking CSFs can prevent and reverse lung inflammation we still need to know a great deal more in order to know if this approach will be useful to treat people in the future. Our project is therefore all about understanding the fine detail of how CSFs can damage the lung. The importance of the project is that our work may lead to entirely new, and much more effective, treatments for people suffering from asthma and COPD.Read moreRead less
This program application seeks to draw on the skills of a world leading group of Australian researchers to bring novel HIV vaccine designs to clinical trials, improve vaccine design and create new opportunities for commercialisation. The Chief Investigators, Prof David Cooper, Prof Peter Doherty (Nobel Prize winner), A-Prof Stephen Kent and Prof Ian Ramshaw, have achieved major scientific developments including: innovative collaborative clinical trials, cutting edge research in T cell immunology ....This program application seeks to draw on the skills of a world leading group of Australian researchers to bring novel HIV vaccine designs to clinical trials, improve vaccine design and create new opportunities for commercialisation. The Chief Investigators, Prof David Cooper, Prof Peter Doherty (Nobel Prize winner), A-Prof Stephen Kent and Prof Ian Ramshaw, have achieved major scientific developments including: innovative collaborative clinical trials, cutting edge research in T cell immunology, the establishment of the only PC3-level nonhuman primate facility in the Southern hemisphere, T cell immunogenicity of the DNA-viral vector prime-boost vaccine regimens and ground-breaking research on cytokine co-expressing viral vector vaccines. The Principle Investigators also have a record of substantial achievement in relation to HIV and T cell biology as well as novel vaccination technologies. There is a strong history of successful collaboration among this group leading to the award of major NIH funding.Read moreRead less
A Randomised Control Trial Of Medical Treatment Versus The Placement Of The Lap Band In Severely Obese Adolescents.
Funder
National Health and Medical Research Council
Funding Amount
$481,905.00
Summary
There has been a substantial rise in the number of overweight and obese adolescents in our community. While prevention of obesity is the ultimate goal, effective stratagies for the management of obese adolescents must be sought. Unfortunately there are few studies that have focused on this problem in adolescents and success has been very limited. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in severely obese (body mass index > 35 kg-m2) adul ....There has been a substantial rise in the number of overweight and obese adolescents in our community. While prevention of obesity is the ultimate goal, effective stratagies for the management of obese adolescents must be sought. Unfortunately there are few studies that have focused on this problem in adolescents and success has been very limited. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in severely obese (body mass index > 35 kg-m2) adults and there are now several small studies that demonstrate its effectiveness in adolescents. Modern obesity surgery involving the keyhole placement of an adjustable band around the very upper part of the stomach has proven to be safe and effective and requires one 24 hr stay in hospital. In this collaborative study, involving the Monash University Centre for Obesity Research and Education and the Royal Children's Hospital, we propose to formally test, for the first time, the effectiveness of a weight loss program that includes adjustable band surgery, and compare this with a comprehensive best care behavioral program, over a period of 2-years in severely obese adolescents. We estimate that suitable subjects will come from the top 1% for body mass index in our community. After thorough assessment 50 suitable candidates with ages ranging from 14 to 18 years will be randomly allocated to one of the two treatment programs. The intensity of each program will be similar. A broad range of measues including: weight, health status, physical disability, psychological status, body image and quality of life, will be performed before and at completion of the 2-year programs. In addition we will compare the complications, compliance and cost of the two programs. This study will help us assess and compare the effectiveness of the 2 programs and provide vital information regarding the role of modern keyhole obesity surgery for the management of severely obese adolescents.Read moreRead less
CAPLA Study: Catheter Ablation For Persistent Atrial Fibrillation. A Multicentre Randomised Study Of Pulmonary Vein Antral Isolation (PVAI) Alone Vs PVAI With Posterior Left Atrial Wall Isolation (PWI)
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Atrial fibrillation (AF) is a common heart rhythm abnormality that affects quality of life with added health care costs. A minimally invasive procedure called catheter ablation (CA) is effective in controlling simple AF (paroxysmal AF) but the best ablation strategy to control a more resistant form of AF (Persistent AF) is unknown. This trial has been designed to address this key gap in knowledge by assessing if adding specific additional ablation to CA will improve outcomes.
A Randomised Controlled Trial Of Magnetic Seizure Therapy In Major Depressive Disorder
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Electroconvulsive therapy (ECT) is the only established treatment for a substantial sub-population of patients who fail to respond to other therapies. However, there are significant complications of ECT including memory related side-effects. The aim of this study is to evaluate the clinical efficacy of a new form of treatment for severe depression, magnetic seizure therapy, which appears to have a substantially reduced rate of cognitive side-effects.