Towards Selective Targeting Of HDACs For Anti-inflammatory Applications
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
HDAC inhibitors are anti-cancer drugs that kill rapidly growing cells (like cancer cells). These drugs also have anti-inflammatory properties and so may be beneficial in chronic inflammatory diseases such as as Rheumatoid Arthritis. However, it is unknown how they reduce inflammation. In this project we aim to understand how HDAC inhibitors act as anti-inflammatory agents and to design new HDAC inhibitors with reduced side effects for the treatment of inflammatory diseases.
The immune system plays an important role in protecting us from infectious diseases. To do this it regulates a series of cell types that must decide upon an appropriate course. In general, this response is successful and protective. However, occasionally the cells make an inappropriate decision leading to problems. For example, allergies are an incorrect response against pollens and dust mites. Similarly, autoimmune disease such as diabetes and multiple sclerosis result from inappropriate attack ....The immune system plays an important role in protecting us from infectious diseases. To do this it regulates a series of cell types that must decide upon an appropriate course. In general, this response is successful and protective. However, occasionally the cells make an inappropriate decision leading to problems. For example, allergies are an incorrect response against pollens and dust mites. Similarly, autoimmune disease such as diabetes and multiple sclerosis result from inappropriate attack upon our own tissues. Despite the clear importance of immune regulation for health, the number of different cell types involved and the complexity of their behaviour has made it difficult to predict and control the response. In this research program a new theory of immune regulation enables the reduction of the complex system to separate components that can be modelled by computer to predict the outcome. An improved predictive framework promises to have a major effect on our understanding and ability to control immune related diseases.Read moreRead less
How IL-4 Suppresses TNF And IL-1 Production By Activated Human Monocytes And Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Chronic inflammatory diseases are an enormous and growing health problem. There is a continuing search for improved and more targeted treatments. We have been studying a cytokine called interleukin-4 which can suppress the production by blood cells of many of the inflammatory mediators that initiate and maintain inflammation. With the recognition that interleukin-4 has this anti-inflammatory activity on blood cells, there was considerable optimism that this molecule may not only be a natural reg ....Chronic inflammatory diseases are an enormous and growing health problem. There is a continuing search for improved and more targeted treatments. We have been studying a cytokine called interleukin-4 which can suppress the production by blood cells of many of the inflammatory mediators that initiate and maintain inflammation. With the recognition that interleukin-4 has this anti-inflammatory activity on blood cells, there was considerable optimism that this molecule may not only be a natural regulator of inflammation but also used in immunotherapy. However we do not know how this molecule downregulates inflammatory blood cells. It will be necessary to know this if it is to be used in human gene therapy for treatment of inflammatory diseases. Cells must be activated before a molecule which is anti-inflammatory can be effective. Different cell types from different inflammatory sites will be studied to better characterise different activation pathways. How interleukin-4 regulates these pathways will be studied. Once identified, treatments based on the properties of interleukin-4 may be designed-optimised.Read moreRead less
Perforin Trafficking And Activation In Killer Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
Perforin (PRF) is a protein essential for the function of cytotoxic lymphocytes during an immune response in humans. Humans deficient in PRF are severely immunosuppressed and fall critically ill if they contract a viral infection. The partial loss of PRF function can also predispose an individual to cancer. We aim to investigate the functional and biochemical properties of PRF. The outcomes of this study will determine how PRF influences the immune system and immune homeostasis in humans.
Investigating Polarity Proteins In Thymocytes- A Potential Role In Asymmetric Cell Division?
Funder
National Health and Medical Research Council
Funding Amount
$69,684.00
Summary
To protect us against infection, surveying immune cells will launch an attack against foreign cells by using complex signalling process to communicate with each other. A novel method in which immune cells differentiate to defend the body against infection has been recently discovered this year and this project will involve dissecting how this occurs. It will involve using state-of-the-art laser-based technologies, combined with studying immune events in cells and intact organs.
Immune Correlates Of Protection Against HCV - A Potential Role For NK Cells And NKR Expression On T Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$72,754.00
Summary
Hepatitis C virus (HCV) poses a major public health problem with ~200 million people infected worldwide and no available vaccine. Injecting drug users (IDUs) are the major risk group, with 75% of infected individuals progress to chronic infection, which can then lead to liver cirrhosis and hepatocellular carcinoma. However, about 20% of a given cohort of IDUs remains uninfected. This project is therefore focused on understanding the innate immune mechanisms behind this protection.
Polynucleotide Vaccine Based On Targeted Delivery To Antigen Presenting Cells
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
We have previously generated a vaccine for breast and other adenocarcinomas by linking a breast cancer associated protein, MUC-1, to a sugar called mannan. This complex was capable of eradicating tumours in mice and its efficacy has been evaluated in human clinical trials (12 in total). As an extension to these studies we have now found that this sugar, mannan, can be used to deliver DNA to immune cells. The current project will evaluate a DNA vaccine for breast cancer.