Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.
Rotavirus is the main cause of severe diarrhoea in children worldwide. In this project, we aim to understand the nature of the first-line immune response to rotavirus in the gut, and elucidate how RV counteracts this response to promote infection. These studies will increase our understanding of how rotavirus causes disease, and facilitate the choice of rotavirus targets for drug development and improved vaccines.
The NF-kB Transcription Factors C-Rel And RelA Control Multiple Steps In Natural CD4 Regulatory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,592.00
Summary
An unfortunate consequence of immune function is that occasionally rogue immune cells are produced that attack the host and lead to the development of so-called autoimmune diseases such as arthritis. Normally a white blood cell called a regulatory T cell suppresses these self-reactive immune cells. We have identified factors that govern the generation of regulatory T cells. Understanding how these factors work should permit the development of new strategies to combat autoimmune diseases. ?
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.
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.
Investigating The Link Between Oxidative Stress And Biomechanical Integrin Activation In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Diabetes represents a serious healthcare problem globally. A large proportion of deaths associated with diabetes can be attributed to the development of blood clots in the circulation of the heart and brain (heart attack/stroke). The blood clotting mechanism is ‘hyperactive’ in diabetes, although the reason for this is not well defined. In this proposal we will investigate a new mechanism promoting blood clots, and will investigate innovative approaches to reduce this clotting mechanism.
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.
Autoimmune-based thrombocytopenia can be a life-threatening adverse event associated with viral load, surgery, drug therapies or the use of the anticoagulant, heparin. This grant will define mechanisms of anti-platelet antibody-dependent platelet activation and assess shedding of platelet-specific glycoprotein (GP)VI as an immediate consequence of this activation, provide a new strategy for evaluating risk of thrombosis in HIT.
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.
Investigation Of The Proinflammatory Function Of Platelets During Ischaemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$552,720.00
Summary
Platelets are important blood cells that stop bleeding. Platelets also regulate inflammation by modulating the function of white blood cells. Excessive stimulation of white cells by platelets may cause tissue damage relevant to a broad of cardiovascular diseases, including heart disease and stroke. This grant application aims to investigate the precise mechanism by which platelets promote inflammation during a heart attack or stroke.