Perinatal Microbe-host Interactions Regulate Neonatal Dendritic Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$1,293,576.00
Summary
Acute lower respiratory tract infections (ALRI) are the leading cause of childhood mortality globally, and increase the risk of chronic lung diseases in later-life. Diverse communities of microorganisms - the microbiome - assemble in infancy and support immune development. In this study, we will explore the relationship between the microbiome and its metabolites, and the expression of an important hormone that regulates the development of the immune system to confer protection against ALRI.
First-in-human Evaluation Of A Novel Immunobiotic To Prevent Respiratory Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,180,080.00
Summary
Respiratory infections are a leading cause of death and illness throughout the world. We have discovered a 'friendly' bacteria that can be applied up the nose to prevent ear infections and the 'flu in mice. We will now test this novel therapy in humans to check it is safe and that it stimulates the human immune system in the same way that it does in mice. This will provide essential information to conduct clinical trials, with the aim to produce a medicine that prevents respiratory infections.
Influenza A Viral Infection And Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$1,346,858.00
Summary
Pregnant women who contract influenza are 5 times more likely to be hospitalised than the general population. Babies of mothers with influenza are also associated with increased perinatal mortality rates. We hypothesise that influenza infection in pregnancy significantly impairs the maternal vascular system resulting in maternal and foetal morbidity. Outcomes from this research may change current treatment modalities to improve maternal and foetal outcomes complicated by influenza infection.
Oleoyl-ACP-hydrolase As An Early Predictive Biomarker For Severe And Fatal Influenza
Funder
National Health and Medical Research Council
Funding Amount
$866,807.00
Summary
Millions are hospitalized with severe influenza disease and ~500K die annually but the underlying mechanisms that drive disease are still not fully understood. We have identified a key role for an enzyme involved in fatty acid metabolism, which is profoundly elevated in patients who succumb to influenza and is thus a predictor for fatal outcomes. This research aims to investigate how this enzyme affects infection and impairs immune responses to drive severe respiratory viral disease.
Silencing Pulmonary Nociceptors To Treat Severe Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$534,173.00
Summary
The lungs receive a rich supply of nerve fibres, many of which play an important role in helping defend against pathogens, including viruses. When viral infections become severe, too much inflammation occurs in the lungs and this creates a serious and difficult to treat clinical problem. Hundreds of thousands of people each year die from the complications of severe lung infections. We are investigating a potential new therapy that targets the lung nerves and relieves excessive inflammation.
Modulating COVID-19 Disease By Targeting Virus And Virus-induced Responses Through Pharmaceutical And Mechanical Ventilation Strategies: SARS-CoV-2 S-protein, ACE2 And TMPRSS2
Funder
National Health and Medical Research Council
Funding Amount
$628,856.00
Summary
COVID-19 is a current global pandemic that is likely to be an on-going threat. We need a multipronged strategy to combat COVID-19, including therapeutic anti-virals and clinical practice management strategy. We will address both these points to define the mechanisms triggering disease, test existing drugs targeting androgens and modify the way doctors use ventilators to treat COVID-19 disease in the intensive care unit. Outcomes will have impact beyond COVID-19 for managing viral lung disease.
An Integrative Approach To Define And Attenuate Genomic Risk Of Coronary Artery Disease
Funder
National Health and Medical Research Council
Funding Amount
$988,454.00
Summary
One in four individuals that have a heart attack do not have traditional risk factors such as high blood cholesterol levels. This highlights the importance of 'family history', which we can now quantify as 'genetic risk'. These studies will determine (i) which genes are important in contributing to this genetic risk (ii) how these genes change biological pathways to increase risk and (iii) the effectiveness of modulating these biological pathways to reduce the risk of heart disease.
HTLV-1 is a lifelong infection of immune cells that sustains high infection rates up to 45% in key Australian communities. Despite HTLV-1 causing serious malignancy and inflammatory co-morbidities that shorten lifespan, few biomedical interventions are available. We will examine how the virus grows and alters immune responses to cause disease. With this, we can develop antiviral treatments to reduce virus infected cells, and make new diagnostic biomarker assays suitable for remote settings.
Structure And Biophysical Analysis Aided Design Of Novel Toxoid Vaccines For A Major Class Of Bacterial Toxins.
Funder
National Health and Medical Research Council
Funding Amount
$608,425.00
Summary
Inactivated bacterial toxins (toxoids), such as the tetanus vaccine, are safe and effective vaccines. Cholesterol dependent cytolysins (CDCs) are bacterial toxins produced by many important human pathogens including Group A Streptococcus (GAS) and Pneumococcus. GAS has no available vaccine and Pneumococcus does not have a universal vaccine. We have developed a new way of inactivating CDCs based on new knowledge of how they target human cells and will use this knowledge to make new vaccines.
Targeting The Crosstalk Between Metabolism And Epigenetics To Treat Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,032,259.00
Summary
Virtually all liver disease related morbidity and mortality is a consequence of fibrosis that culminates in liver failure or liver cancer. Since anti-fibrotic drugs are not available, new approaches to drug development are required. We have discovered a novel strategy for such drug development by modifying the expression of a specific gene (RARRES1) in a highly targeted manner and thereby interrupting the energy production that is needed by cells to drive fibrosis.