Identification Of Novel Mediators Of Bone Catch-up Growth
Funder
National Health and Medical Research Council
Funding Amount
$1,043,810.00
Summary
Musculoskeletal growth disorders cause significant suffering in children and impair new workforce generations before their working life starts. Despite this relevance, non-invasive methods to induce growth recovery of impaired bones are an unmet need, as we lack sufficient understanding of how this process works. To address this knowledge gap, we generated mouse models that will allow us to reveal foetal mediators of compensatory growth that could be reactivated postnatally to boost bone growth.
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.
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.
Developing An In Vitro Model Of A Human Blastocyst
Funder
National Health and Medical Research Council
Funding Amount
$890,062.00
Summary
Using novel cellular and molecular technologies we propose to develop an artificial model of an early human blastocyst. This will allow us to study the first initial steps in human development without the use of real embryos. Such a model will not only help us decipher the first steps in human development, but we anticipate it will be essential to study how gene mutations and the environment affect this initial step in human development.
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.
A New Mechanism Of Tissue Fibrosis - A Small Peptide Regulator Of The TGF-beta1/Smad Pathway
Funder
National Health and Medical Research Council
Funding Amount
$768,757.00
Summary
Progressive scarring, or fibrosis, of organs leads to their loss of function. Fibrotic diseases are devastating to both the individual and our community and we lack effective therapies. We have identified a small protein, named SPRF, which represents a new mechanism in tissue fibrosis. These studies will examine the role of the SRPF protein in models of kidney, heart and lung fibrosis and its underlying mechanism of action. We will also test a therapy based on inhibiting SPRF function.
The Cellular Basis Of Synaptic Integration And Modulation In Human Pyramidal Neurons
Funder
National Health and Medical Research Council
Funding Amount
$917,355.00
Summary
Little is known about how human neurons integrate information, and how this process is altered during neuromodulation and disease. This project will address this fundamental gap in knowledge and will for the first time directly examine the neuromodulation of human neurons, and how this important process is altered in brain cancer. Our team of researchers and surgeons in Melbourne and Berlin will be able to provide valuable, and otherwise unattainable, information about the human brain.
Preventing The Transition From Acute To Chronic Pain. The Role Of Neural And Non-neural Factors.
Funder
National Health and Medical Research Council
Funding Amount
$2,998,900.00
Summary
Pain following injury usually dissipates as the injury heals, however in some individuals it persists and lasts for years. Chronic pain is extremely difficult to treat, particularly that which originates from a damaged nerve. One of the roadblocks in developing effective treatments is our limited understanding of the pathophysiology. The overall aim of this proposal is to address this gap and determine the processes that occur in the brain that results in acute pain transitioning to chronic.