S100A8/A9 As A Target In Metabolic Diseases To Inhibit The Acceleration Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$554,990.00
Summary
Obesity and diabetes are the leading cause of premature death, due to accelerated cardiovascular disease (CVD). The abundance of blood monocytes influences the progression and regression of CVD. We discovered that S100A8/A9 promotes monocyte production in obesity and diabetes. This project will explore how S100A8/A9 is produced in diabetes and obesity and if blocking its function using a novel drug will prevent obesity and diabetes associated CVD.
Mechanisms Of Novel TLR9 Mediated Intraocular Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$442,244.00
Summary
Corneal opacities and scarring due to microbial and parasitic infections are a major cause of blindness globally. Novel studies in our lab have shown that topical application of bacterial/viral DNA alone to the cornea can cause previously unrecognised inflammation in the retina. Understanding the mechanisms of this retinal inflammation and how to block it may help in the design of novel treatments for a number of blinding conditions.
M2 Macrophage Polarization As A Cause Of Vascular Fibrosis And Stiffening In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$657,028.00
Summary
Blood vessel stiffening is a hallmark of hypertension (A.K.A. high blood pressure) and is thought to be a major contributor to the clinical complications of the condition, which include heart failure, stroke and renal impairment. Here we will test the novel concept that this stiffening process is caused by certain types of white blood cells (macrophages), which enter the walls of blood vessels and signal the surrounding cells to produce a rigid scaffolding protein called collagen.
A Nanomedicine Strategy For Detecting And Modulating Protease Activity In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$455,534.00
Summary
Protease enzymes are vitally important for normal bodily function but can play a deleterious role in many diseases such as cancer, aging diseases and eye diseases. The proposed research will provide a nanomedicine solution to the detection and therapeutic control of protease activity in vivo using nanoporous optical devices that are benign to the body. This general strategy for will be demonstrated in eyes with a view to detection and treating the eye disease uveitis.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
The Novel Role Of Eukaryotic Elongation Factor 2 Kinase (eEF2K) In Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$650,531.00
Summary
Atherosclerosis causes build up of cholesterol plaques inside blood vessels that cause heart attacks and strokes. Macrophages are a type of cell that accumulate inside these plaques to make them grow. We work with a molecule called eukaryotic elongation factor 2 kinase (eEF2K), that controls how cells in the body divide and survive. We are studying how eEF2K controls the macrophage build up in plaque to develop new treatments against atherosclerosis that can stop heart attacks and strokes.
Mineralocortioid Receptor-Mediated Injury In Progressive Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$707,008.00
Summary
Diabetes is the major cause of kidney failure. Activation of a hormone receptor (the mineralocorticoid receptor-MR) can promote kidney injury. Current drugs blocking MR can suppress diabetic kidney disease but are limited by their poor specificity and harmful side effects. Our study will help improve strategies for blocking MR by identifying the cell types responsible for MR-mediated injury and by examining whether a new class of drug targeting MR is a superior therapy to current MR inhibitors.
Clinical Implications Of Trans-kingdom Microbial Interactions In The Transplanted Lung
Funder
National Health and Medical Research Council
Funding Amount
$631,909.00
Summary
Lung transplantation is a critical requirement for people with severe lung diseases. The lung is constantly exposed to bugs and viruses, which reside in the airways, and can be both beneficial or detrimental for lung health. This interaction between the immune system and these bugs can influence the health and longevity of the lung transplant. We aim to discover how we could target these interactions to improve the long-term success of lung transplantation.
The Role Of IL-17 In Regulating Liver Macrophage Permissiveness For Leishmania Infection
Funder
National Health and Medical Research Council
Funding Amount
$655,082.00
Summary
Visceral Leishmaniasis is a disease of poverty in the developing world caused by Leishmania parasites, which live and replicate within host tissue macrophages. A cytokine produced by host cells, IL-17A impairs the ability of liver macrophages to control this infection, as mice that lack IL-17A have lower parasite burdens in the liver after experimental infection. We propose to investigate if IL-17A mediates this impaired control by tuning the permissiveness of host macrophages to infection.
Immunomodulatory Properties Of Amnion: From Pregnancy To Regenerative Medicine
Funder
National Health and Medical Research Council
Funding Amount
$446,349.00
Summary
Cells from the placenta have been shown to have regenerative capabilities, repairing injured tissues. In this research we aim to explore how the cells do this. In particular we will address how transplanted placental cells talk to the recipient's immune cells to better coordinate tissue repair and prevent scarring. In short, we aim to learn how these cells coordinate immune function during pregnancy to then apply this knowledge to regenerative medicine.