Targeting The NLRP3 Inflammasome And Interleukin-18 In Hypertensive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$1,241,115.00
Summary
Heart failure is a common complication of hypertension and a major cause of death and disability worldwide. This project will characterise a newly identified inflammatory pathway that we believe to be a major cause of the enlargement and scarring of the heart that accompanies hypertension. We will also trial drugs that block this inflammatory pathway to determine their suitability as future therapies for this devastating disease.
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.
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.
Targeting Inflammatory Skin Disease Using An Immune-modulatory Human Signal Peptide
Funder
National Health and Medical Research Council
Funding Amount
$698,836.00
Summary
Effective drugs are desperately needed for the improved treatment of inflammatory diseases. We will determine how a modified human peptide, which we have discovered and can make, works to suppress harmful skin inflammation. We will design new formulations to deliver our drug to the skin in order to better treat psoriasis, an autoinflammatory skin disease. We will also trial our new drug in models of atopic dermatitis a debilitating skin disease for which there is limited treatment options.
Exploiting Anti-capsid Humoral Immunity Induced In Infants Receiving Gene Therapy For Spinal Muscular Atrophy To Engineer The Next Generation Of Gene Transfer Vectors
Funder
National Health and Medical Research Council
Funding Amount
$1,105,993.00
Summary
After 25 years of incremental progress the possibility of treating genetic disease by gene therapy has become a therapeutic reality. This has been achieved by harnessing the gene transfer power of viruses made harmless by genetic engineering. A major limitation is that up to 50% of patients are currently excluded by pre-existing immunity to these powerful tools. Using 'evolution in a dish', we will engineer a new generation of these tools capable of bypassing pre-existing immunity by stealth.
Antibiotic Conjugates: Joining Together To Fight Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$697,675.00
Summary
New strategies are urgently needed to treat the rise of infections from multidrug-resistant bacteria, with standard antibiotic therapies becoming obsolete. This project will develop multiple innovative approaches to overcome antibiotic resistance, based on a core concept of appending additional functionality to existing antibiotic scaffolds. New conjugates will be synthesized, tested for antimicrobial activity, then optimized via a validated antimicrobial development pipeline.
Immunomodulatory Vaccines In The Treatment Of Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$678,899.00
Summary
Peanut allergy is the most common cause of food-induced anaphylactic reactions in Australia and is a major burden to our healthcare system. Current clinical practice advice dietary avoidance to prevent fatal anaphylactic responses. We propose the use of an immunomodulatory vaccine to re-write the immune response to peanut antigens, from an allergic to a tolerant phenotype. This study will provide novel insights into rational approaches for manipulating immune memory to food allergens.
Targeting Antimicrobial Resistance And Host Immune Evasion In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$892,831.00
Summary
This project aims to show how one of the most important human superbugs, Staphylococcus aureus (Golden staph), develops resistance to one of our most important last-line antibiotics and the immune system to cause life-threatening infections. Our work will also investigate and test new treatment strategies for this common and challenging human pathogen.
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.