Treating and preventing painful fractures could be improved by strengthening cortical bone – the hard outer shell of all bones in the skeleton. We don’t know how cortical bone forms, but if we did, we could improve its strength. We have found that a brain-like network of cells inside the skeleton, called osteocytes, use a specific signal, called SOCS3, to make strong cortical bone. This study will find out how SOCS3 works and find new ways to make cortical bone strong and healthy.
Immune Balance-regulating Interleukins As Targets For Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
The immune balance is crucial to human health. Interleukins are a group of proteins secreted by immune cells to mediate their communication. They tune up or down immune responses, thus as attractive targets for immunotherapy to restore the immune balance to treat autoimmune diseases, allergies and infections. This fellowship will support translational research to develop Interleukin-2 (IL-2) and IL-21-based novel immunotherapies for autoimmune disease, infection and allergy.
Inflammasome Function In Gastrointestinal Immunity And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$421,116.00
Summary
The immune system in the gut provides a vital defence against microbes. If these defences are ineffective we become infected leading to gastroenteritis, a major cause of death in the third world and hospitalisation in developed countries. Conversely, excessive or inappropriate activation of these defences can cause inflammatory disease. This project will investigate microbial detection in the gut, and aims to discover new, more effective ways to treat gastrointestinal infection and inflammation.
IL21, B-cell Proliferation And The Mechanism Of Memory Formation
Funder
National Health and Medical Research Council
Funding Amount
$981,896.00
Summary
Our immune system can ‘remember’ old infections, which is why we do not suffer from the same pathogen multiple times and why vaccines work. Much of this protection is due to memory B-cells, of which there are different kinds. We think the different memory B-cell subsets have different functions and understanding how they are made and how this is controlled will help us improve responses to critical infections – HIV, Flu – and in critical patient groups – aged people and transplant recipients.
We have identified a microRNA (miRNA) which can elicit the functional outcome of the anti-inflammatory cytokine IL-10. miRNAs constitute a novel mechanism used by cells to regulate gene expression and have shown much promise as a therapeutic tool. Our finding suggests that modulation of miRNAs through the use of miRNA mimics or antisense technology may serve as an alternative and/or synergistic approach for the use of IL-10 as therapy in chronic inflammation.
Dissecting Apoptosis And IL-15 Dependent Homeostasis Pathways Of Natural Killer (NK) Cells
Funder
National Health and Medical Research Council
Funding Amount
$423,809.00
Summary
We will investigate how the cytokine IL-15 regulates the homeostasis of natural killer (NK) cells. NK cells are critical for immune responses against invading viruses or bacteria or upon detection of transformed cells. NK cells are primed to attack infected or transformed cells and are rapidly activated by direct interaction or by soluble signals. Knowledge of how NK cells development and how their numbers and function are controlled is paramount to understanding infectious disease immunology an ....We will investigate how the cytokine IL-15 regulates the homeostasis of natural killer (NK) cells. NK cells are critical for immune responses against invading viruses or bacteria or upon detection of transformed cells. NK cells are primed to attack infected or transformed cells and are rapidly activated by direct interaction or by soluble signals. Knowledge of how NK cells development and how their numbers and function are controlled is paramount to understanding infectious disease immunology and developing better immuno-therapies.Read moreRead less
Targeting Inflammation As A Biomarker And Treatment For Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$718,920.00
Summary
We are undertaking the challenge of using and developing novel animal models in parallel with studies on affected human subjects to elucidate the underlying molecular mechanisms linking the changes in inflammation to amyloid plaques, neurofibrillary tangles and cognitive decline. Understanding these mechanisms will allow us to define the biological pathways involved in the onset and progression of Alzheimer’s disease, and identify potential biomarkers and therapeutic targets.
Interleukin-1β Biology: Mechanisms Of Regulation, Activation And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$641,979.00
Summary
The protein called intelreukin-1 (IL-1) is required to fight off invading pathogens but more recently has been implicated as contributing to diverse diseases characterised by excessive inflammation, such as arthritis, gout, atherosclerosis and even cancer. This project aims to understand how IL-1 is made within cells and then activated to cause inflammation, which will enable these processes to be therapeutically targeted.
Il-18 helps to prevent obesity and type 2 diabetes, however the process by which this cytokine is activated to prevent obesity is not known. We have now found the pathway that drives to this process. This project will seek to extend our observations to show how this can be targeted therapeutically to treat obesity and type 2 diabetes.
Chemokine Receptors And The Control Of Th17-mediated Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$801,229.00
Summary
Controlling persistent inflammation in autoimmune diseases is a major challenge and current therapeutics have significant side effects. Thus, novel targets must be identified. We have discovered a previously unknown level of control of autoimmune inflammation that may represent a more specific and effective means of controlling ongoing inflammation in these diseases.