Phagocytic Clearance And Immune Activation In Malaria
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
Macrophage white blood cells clear malaria infected cells by eating them, by three routes- by recognising ANTIBODIES or COMPLEMENT on the cell surface, or by the cell BINDING directly to the macrophage. Each has different results, such as amounts of cytokines produced. Cytokines clear malaria; in excess they can cause fatal immune pathology. We will investigate how variations in amount of antibody and complement and route of uptake of malaria infected cells might determine malaria outcome.
Signalling Pathways In Antibody-Mediated Renal Injury
Funder
National Health and Medical Research Council
Funding Amount
$113,296.00
Summary
Many types of kidney disease are induced by antibody binding to the kidney which initiates a damaging response by cells of the immune system. Current therapies for such diseases rely upon toxic immunosuppressive drugs. This project will examine one specific mechanism by which immune cells are activated by antibody to cause injury in human and experimental renal injury. These studies will determine whether this specific mechanism is a suitable target for developing new therapeutic drugs.
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.
Kidney Injury As A Determinant Of Macrophage Phenotype And Efficacy For Treating Chronic Kidney Disease (CKD)
Funder
National Health and Medical Research Council
Funding Amount
$548,341.00
Summary
Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or tranplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Macrophage infiltration of kidneys is characteristic of C ....Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or tranplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Macrophage infiltration of kidneys is characteristic of CKD, and it has been assumed that macrophages cause damage. However, we have shown that certain types of macrophages can reduce kidney damage. This project will explore whether macrophage type can be switched from that causing damage to that reducing injury, with the aim of using this approach to treat CKD.Read moreRead less
The Effect Of Titanium Surface Modification On The Immuno-regulation Of Osseointegration.
Funder
National Health and Medical Research Council
Funding Amount
$308,713.00
Summary
Titanium implants are an established treatment modality in both dentistry and orthopaedics. This project will determine how implant surface modification can modulate the inflammatory response and subsequent differentiation of stem cells involved in the process of integrating the implant with bone i.e. osseointegration. The identification of the molecular mechanisms involved will thus provide leads for novel ways to further to enhance the osseointegration process and improve clinical outcomes.
Synovial Macrophages And T-cells Are Therapeutic Targets In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$658,761.00
Summary
Osteoarthritis (OA) is the most widespread musculoskeletal disease in Australia and there are currently no therapies that halt disease progression. Specific inflammatory events play a pivotal role in initiating and driving OA progression. In this study we will define the specific inflammatory cells involved in OA, how and why they change with time, and which can be targeted to stop disease onset and development. This will provide the platform for initiating human clinical trials.
Macrophages are important cells at the front-line of immunity where one of their main roles is to release anti-bacterial proteins. We will study the macrophage molecules, subcellular organelles and pathways that help to release these proteins to kill bacteria and fight infection. Our studies will identify new cellular targets for boosting immunity and treating inherited diseases with defective macrophage function.
After infection with viruses, parasites and bacteria the protein SerpinB2 becomes very abundant in macrophages, which are white blood cells involved in inflammation. Unfortunately, what this protein is doing is very unclear. We have found that macrophage SerpinB2 dampens the responses of other immune cells. This grant aims to determine how this is achieved and thereby help resolve the role of this protein in a number of diseases such as cancer, lupus, asthma and pre-eclampsia.
Cigaratte Smoke Exposure Suppresses Alveolar Macrophage Responses To Lipopolysaccharide By Modifying The TLR4 Pathway
Funder
National Health and Medical Research Council
Funding Amount
$506,283.00
Summary
Long term cigarette smoke exposure is a major risk factor for cancer, heart disease and emphysema. A less known fact about smoke exposure is that it also leaves people susceptible to respiratory infections by i) physically damaging the lung lining and ii) suppressing cells responsible for coordinating the lungs defence system. This project will identify how smoke exposure blocks the early response to infection by the immune system and discovery novel ways of restoring normal lung defences.