Dynamics And Mechanisms Of Neutrophil Migration During Tissue Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
Neutrophil granulocytes are central mediators of inflammatory conditions and infections. It is currently unclear how neutrophils navigate through inflamed tissues and how they detect damaged cells and/or pathogens. This proposal will use cutting-edge multi-photon microscopy to dissect the dynamics and mechanisms of neutrophil behaviour in real time in living animals. These experiments will provide a new understanding of the development of inflammatory diseases.
The Role Of Perivascular Macrophages In The Regulation Of CNS Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$602,609.00
Summary
Inflammation of the central nervous system can have deleterious consequences. How the inflammatory cascade operates within the CNS is poorly understood. We have recently discovered a novel subset of immune cells, the perivascular macrophage, which regulates the recruitment of inflammatory cells. Aim of this proposal is to dissect the role of these cells during brain infections and autoimmune inflammation.
THE ROLE OF THE TETRASPANINS CD37 AND CD82 IN LEUKOCYTE MIGRATION
Funder
National Health and Medical Research Council
Funding Amount
$370,902.00
Summary
White blood cells must be able to migrate to fight infection. For instance, immune responses are started by the migration of one type of white blood cells to the lymph node. Also, once activated white blood cells migrate out of the circulation to the site of infection where they can kill bacteria and viruses. This grant studies 2 proteins that control white blood cell migration. These proteins may one day be targets for drugs that either promote immunity or reduce inflammation.
The Role Of Perivascular Macrophages In The Regulation Of Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Neutrophils are key defenders against bacterial infections. In this application we will test the hypothesis that perivascular macrophages play a critical role in the recruitment of neutrophils to site of cutaneous infection, and that these cells are targeted and destroyed by bacterial virulence factors. Our studies will gain novel insight into the leukocyte homing paradigm and shed new light on the mechanisms of microbial immuno-evasion.
Mechanisms Of Alpha-hemolysin Induced Immunoevasion By Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$465,475.00
Summary
S. aureus infections represent a serious global health problem. Currently, no vaccination is available demanding a better understanding of the immune response against this bacterium. We will test the hypothesis that S. aureus alpha-hemolysin represses the migration of innate immune cells to sites of cutaneous infection resulting in diminished immunity. Unraveling the mechanism behind this phenomenon will pave the way to better prophylactic and therapeutic measures against S. aureus infections.
Mechanisms Of Immune-evasion By Group A Streptococcus During Skin Infection
Funder
National Health and Medical Research Council
Funding Amount
$602,609.00
Summary
Infections by Group A Streptococcus (GAS), or Streptococcus pyogenes, represent a global health concern. Currently no vaccine exists against GAS thereby mandating a better understanding of the immune response against the bacterium. Using in vivo microscopy, the aim of this proposal is to dissect in real time how neutrophils detect and destroy GAS following skin infection, and how the bacterium manages to circumvent the attack by innate immune cells.
Neutrophil Regulation Of Early Adaptive Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$613,273.00
Summary
The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammator ....The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammatory diseases.Read moreRead less
Neutrophil-macrophage Co-operation In The Resolution Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$325,854.00
Summary
Failed inflammation resolution is at the core of many diseases and has a significant impact on the progression of cancers and atherosclerosis. Visualising and manipulating inflammation in zebrafish has led to key discoveries. Neutrophil-macrophage interactions may be a key process regulating inflammation resolution, and understanding this process better at a molecular level is likely to identify important pathways that might be manipulated for the benefit of patients with chronic inflammation.
As the first recruited cells, neutrophils direct protective responses against infection, but can also mediate destructive responses in inflammatory disease. This project will determine mechanisms driving neutrophil-dependent inflammation in both settings, by examining a specific inflammation-promoting molecular pathway (the ïinflammasomeÍ) in neutrophils. This research will lead to a better understanding of inflammation, and may suggest therapeutics for treating inflammatory disease.