Molecular Regulators Of Adaptive Immunity To Overwhelming Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$786,898.00
Summary
Diseases caused by overwhelming viral infections, such as COVID-19, are associated with widespread impairments in immunity and constitute a major burden to human health. We have discovered that the molecule c-Myb is essential for the maintenance of immunity during chronic infection. In order to lay the foundations for novel and innovative anti-viral therapies, this project will dissect the molecular pathways regulated by c-Myb that maintain immunity during severe or chronic infection.
Development Of National Protocols For The Detection Of Influenza A H5N1
Funder
National Health and Medical Research Council
Funding Amount
$248,229.00
Summary
This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patie ....This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patient specimens. Australian laboratories need authoritative guidelines as to optimal influenza tests, target genes and reagents. Development of a simple, potentially automated type specific test for influenza A H5N1 antibody such as enzyme immunoassay (EIA) is also desirable, as widely used tests cannot distinguish between infection with H5 or other influenza types. Reference methods such as haemagglutination inhibition (HAI) are cumbersome. In this project mock specimens for virus and antibody detection will be created using viral cell culture and infected chicken derived influenza A H5N1. This will be undertaken in physical containment level 4 (PC4) facilities in Australia's designated human and animal PC4 laboratories. This material will be used for (i) specimen panels to compare the performance of candidate laboratory tests (ii) positive control material in all tests undertaken and (iii) quality assurance exercises to ensure high standards of testing. Using these panels the group will assess influenza H5N1 RT-PCR, tests for detection of influenza proteins including immunofluorescence, and rapid point of care influenza A detection tests available in Australia. An EIA method currently used to detect influenza antibodies from different animal species will be refined to develop a simple test for type specific detection influenza A H5N1 antibodies, and subsequently evaluated using animal sera. A standard method for HAI reference serology for use in public health laboratories will also be recommended, and the best approaches to high throughput automated RT-PCR, and performing RT-PCR in the field on portable instrumentation will be explored. Recommendations for standard protocols for influenza A H5N1 will be developed and will submitted for review and endorsement by Commonwealth ministerial advisory committees.Read moreRead less
In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an i ....In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an important process in both the development and progression of asthma. The reason why remodelling occurs in the lungs of people with asthma is not known. It is thought that persistent inflammation drives the remodelling process; however remodelling can perpetuate inflammation, thereby creating a cyclic series of events. Furthermore we have shown that cells from non-asthmatic volunteers which are grown on asthmatic ECM change to become more like cells from asthmatic subjects. Viruses which infect the lungs may play a role in the development of asthma, and in the increased remodelling which is observed. Many common respiratory viruses are capable of infecting lung cells, eg epithelial cells, which evokes an inflammatory response. I will investigate if viral infection can alter the remodelling process, using lung cells isolated from asthmatic and non-asthmatic volunteers. Furthermore, I will assess if current and novel treatments are effective in reducing the remodelling process. We have preliminary evidence that infection of lung epithelial cells with rhinovirus (the common cold virus) alters the amount of ECM deposited by these cells. I hypothesise that this process will be increased in cells from volunteers with asthma compared to non-asthma. As current therapeutics are unlikely to be able to reverse these remodelling events these experiments will enable the development of new therapeutics which can target this important aspect of airway disease.Read moreRead less
Chronic obstructive pulmonary disease (COPD) is a chronic lung condition caused by cigarette smoking. COPD consists of emphysema and chronic bronchitis, which lead to worsening breathlessness, cough and sputum production and need for oxygen. COPD is the third highest cause of burden of disease to the community in Australia and the fourth leading cause of death. People with COPD suffer many chest infections, which need antibiotics and offer need admission to hospital. However there is much variab ....Chronic obstructive pulmonary disease (COPD) is a chronic lung condition caused by cigarette smoking. COPD consists of emphysema and chronic bronchitis, which lead to worsening breathlessness, cough and sputum production and need for oxygen. COPD is the third highest cause of burden of disease to the community in Australia and the fourth leading cause of death. People with COPD suffer many chest infections, which need antibiotics and offer need admission to hospital. However there is much variability in the pattern of COPD related to infections. Natural chemicals produced by the body that fight infection are likely to be involved in this variability. Recently it has been discovered that there are variations in the genetic sequence of the genes that code for these chemicals. These genetic variations change the structure of the chemicals or the rate at which they are produced. Therefore it is highly likely that these genetic variations may influence the risk of developing COPD, and the risk of getting infections. In this study, we aim to systematically examine how these genetic variations alter the development of COPD and the risk of infections. At the start, we will collect a blood sample and phlegm (sputum) specimen from each person. The results of the genetic tests will then be compared to the risk of developing COPD, the chemicals produced and the risk of infection. We believe this study will improve our understanding of how COPD and its complications develop, leading to better treatment for this condition in the future.Read moreRead less
The Intracellular Replicative Niche Of Legionella Species And Coxiella Burnetii.
Funder
National Health and Medical Research Council
Funding Amount
$529,632.00
Summary
This project will study how the bacterium that causes Legionnaire's disease survives and grows inside human cells. We have identified new bacterial proteins that allow Legionella to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Coxiella, which causes Q-fever. By determining how these proteins act, this work may result in new treatments for Legionnaire's disease and related infections.
A Prospective Randomised Trial Comparing Nasogastric With Intravenous Hydration In Children With Bronchiolitis
Funder
National Health and Medical Research Council
Funding Amount
$886,817.00
Summary
This project aims to compare the two methods currently being used of providing fluid to young children who have a viral infection of the lungs called bronchiolitis. The methods of giving fluids are through a tube placed though the nose, down the food pipe, into the stomach (nasogastric tube), or through a drip in the child's vein (intravenous). We hope to show that one of these methods is better than the other and allows children to be sent home from hospital earlier, and cost less.
RNAi Therapeutic Intervention Of Human Viral Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$584,117.00
Summary
Human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. HMPV is emerging as a major cause of morbidity and life-threatening respiratory tract disease in infants, young children and the elderly worldwide. No treatment is currently available. The objectives of this proposal are to develop novel antiviral drugs that silence the expression of viral genes and to examine protection against the disease.