Resolving Eosinophil And Inflammatory Heterogeneity In Chronic Allergic Airway Disease For Safer, Effective And Lasting Precision Therapies
Funder
National Health and Medical Research Council
Funding Amount
$1,166,165.00
Summary
Many patients with upper airway inflammation and asthma have poorly controlled disease and are in need of new effective therapies. We have discovered new cell subsets in the airways of these patients. We will use cutting edge single cell and spatial analysis of human tissues to define human allergic disease and inflammatory cells at unprecedented resolution. This will identify new targets for treatment and match patients with effective therapies to facilitate precision therapy.
ER Stress-Unfolded Protein Response A Critical Metabolic Pathway For Airway Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$789,475.00
Summary
Airway remodelling in asthma is associated with poor clinical outcomes and is not prevented by current treatments. We have found endoplasmic reticulum stress (ERS) and associated unfolded protein response (UPR), a crucial process involve in cellular protein folding, play a key role in airway remodelling in asthma. This study will investigate whether inhibition of ERS prevents goblet cell metaplasia, mucus hypersecretion and fibrosis and can be used as a therapeutic strategy for severe asthma.
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.
Targeting Neurovascular Communication As A Novel Way Of Reducing Vision Loss In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$986,663.00
Summary
Diabetes is a leading cause of blindness. Here, we evaluate whether diabetes causes changes in the way neurons signal to blood vessels, and whether blocking some of the signals from neurons reduces blood vessel abormalities. Overall, this information is critical to our understanding of the early changes that occur during diabetes and whether novel treatments used early in diabetes can prevent long term changes and vision loss.
Dissecting Brain Network Ageing Using Whole Brain Imaging
Funder
National Health and Medical Research Council
Funding Amount
$692,964.00
Summary
In this proposal, we will make the first attempt to map the whole brain activity change during ageing using a series of state-of-the-art techniques. We will also identify genetic and pharmacological interventions that improve brain network function during ageing. Outcomes from this research will provide an unprecedented understanding of functional ageing within the brain and identify therapeutic interventions to prevent this process.
Organisation Of The Genome During The Development Of Antibody-secreting Cells
Funder
National Health and Medical Research Council
Funding Amount
$886,155.00
Summary
Each cell of our body contains over two metres of DNA that must be correctly packaged in order for our cells to function. We are using cutting-edge molecular biology techniques to study how this DNA circuitry is established in the white blood cells of our immune system that produce antibodies. Our novel approaches will reveal unique strategies to modulate immune responses to our benefit.
A Novel Interaction Between The Immune And Vascular Systems In Early-onset Preeclampsia; An Opportunity For New Treatments?
Funder
National Health and Medical Research Council
Funding Amount
$921,623.00
Summary
Preeclampsia is a pregnancy complication that leads to poor birth outcomes and elevated lifelong cardiovascular disease risk in 4 million women each year. It has no cure and treatments are limited because the causal mechanisms are not understood. We have identified a specialised immune cell in the mother's blood that assists blood vessels to function properly in pregnancy. We will assess whether interventions to enhance these cells can improve poor blood vessel function and pregnancy outcomes.
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.