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Harnessing Tyrosine Metabolism To Combat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$866,467.00
Summary
Cross-talk between our immune system and the microbiome is central to health and disease. In particular, the gut microbiome has wide-ranging effects throughout the body, in part through the production of metabolites with immunomodulatory activity. We have discovered a novel subset of microbial metabolites which can protect mice against allergic airway inflammation, a model of asthma. We now aim to discovery how these metabolites work with a view towards developing them as therapeutics.
Molecular Dissection Of Allergen Sensitisation And Immunotherapy: Direct Application To Precision Medicine In Treatment Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$1,270,097.00
Summary
Asthma is a major global health burden with huge socioeconomic impact. Most asthmatic patients are allergic. Allergen immunotherapy is the only treatment to alter the natural disease course, but does not work in many treated patients, and robust laboratory biomarkers for patient selection and immune monitoring of treatment success are lacking. Therefore, allergen immunotherapy is not offered to most patients who then rely on medications indefinitely. This research will address these needs.
Vaccine To Prevent Influenza Virus And Bacterial Super-infection.
Funder
National Health and Medical Research Council
Funding Amount
$707,717.00
Summary
Influenza viruses have the ability to pre-dispose infected hosts toward secondary bacterial complications. The mortality of viral infections that are complicated by a concurrent, or subsequent, bacterial infection (known as a super-infection), is often greater than that of either the virus or the bacteria alone. We will develop a novel multi-pathogen vaccine candidate against the major upper respiratory tract pathogens - Influenza A and Streptococcus pyogenes to prevent super-infections.
Inflammasome Sensors And Immune Protection Against Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$750,110.00
Summary
Intestinal cancer is a leading cause of death in Australia and worldwide. Defects in the immune system can lead to the development of intestinal cancer. In this project, we will investigate the critical role of an immune sensor in inhibiting the development of intestinal cancer. This project will provide new insights into the interplay between the immune system and cancer biology and will potentially inform the development of new immunotherapies.
Current therapy for AAV has major toxicities and 30% of Patients are dead or on dialysis within 3 years. This proposal aims to study a unique form of cell death termed Neutrophil extracellular traps (NETs) that initiates and perpetuates inflammation in this disease. We will use an animal model of the disease that mirrors human disease. We will inhibit crucial molecules in NET production to attenuate disease. This will provide proof of concept evidence to promote clinical trials in patients.
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.
Intergenerational Impacts Of Paternal Immune Activation On Brain Function And Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$997,690.00
Summary
We recently discovered that infection of male mice with a parasite (Toxoplasma gondii) before conception can change the epigenetic information in the sperm and alter behaviour of the offspring. This is the first evidence that pathogenic infection in males can affect the next generation. We will investigate how infection with other major pathogens, including bacteria and the virus causing COVID-19, may affect sperm epigenetics and offspring health, including their brain function and dysfunction.
Coordinating Neuroimmune Sensory Networks In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$884,405.00
Summary
Living organisms use cellular rhythms to optimize their energy use and cellular responses. Our proposal aims to produce significant new fundamental knowledge by elucidating the fundamental cellular and molecular biology of innate cells, their role in mucosal homeostasis and tissue repair pathways in the gut. Understanding this foundational process of cellular regulation will generate new basic knowledge and may lead to better management systems.
Amyotrophic Lateral Sclerosis (ALS) is a progressively fatal neurodegenerative disease characterized by aggregates of a protein called TDP-43. ALS also features the presence of several inflammatory cytokines in the central nervous system. In this project, we will study how TDP-43 abnormally mislocalizes within cells, releasing mitochondrial DNA and triggering a novel pathway of inflammation. We propose that targeting this pathway could lead to new treatments for ALS.
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.