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.
Wheat Proteins, The Duodenal Microbiome And Immune Activation In The Aetiopathogenesis Of Non-coeliac Gluten Sensitivity And Functional Dyspepsia
Funder
National Health and Medical Research Council
Funding Amount
$1,997,150.00
Summary
Functional dyspepsia, characterised by troublesome pain in the upper abdomen, or an inability to finish a regular sized meal, is common, affecting up to 15% of Australians. There are no effective treatments. This project will evaluate the role of diet, in particular wheat, as a driver of the subtle inflammation and disturbances in the microbiome seen in the small intestine of functional dyspepsia patients, and test whether a gluten or wheat free diet is an effective treatment option.
Presentation Of Metabolite Antigens By MR1 Molecules: A Fundamental System Of Immune Priming
Funder
National Health and Medical Research Council
Funding Amount
$883,832.00
Summary
Our immune system constantly monitors our body for disease-causing microbes, such as bacteria that cause illnesses like pneumonia or tuberculosis. Our cells have a molecular alarm-system called 'MR1' which alerts white blood cells that an infection by microbes is occurring, however this process is not well understood. This grant will allow me to discover the cells and molecular pathways that govern the MR1 alarm system, which may lead to new treatments against common diseases in our community.
Ovarian cancer is difficult to diagnose, patients present at a late stage of disease and it responds poorly to therapy. To improve treatment, it is crucial to gain new insights into ovarian cancer biology. We discovered a new protein, interferon epsilon, which is produced naturally by cells lining the female reproductive tract where it protects against infections and may even prevent development of cancers. We plan to characterise the action of IFNe on HGSOC and how best to use it for therapy.
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.
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.