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Role Of The Mast Cell Product Histamine In Ultraviolet Radiation Induced Systemic Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise ab ....The harmful effects of ultraviolet radiation on skin, as exemplified by sun exposure, are well recognised: sunburn, premature ageing of skin, and induction of skin cancer. Indeed, skin cancers are the most common cancers in Australia. Increasingly recognised now is that UV radiation can alter the immune system. This is of particular relevance to the development of skin cancer: alteration of the immune system is critical to outgrowth of UV-induced cancers. The intact immune system is otherwise able to reject the great majority of UV-induced skin cancers. This effect of UV radiation on the immune system may be relevant to other diseases. It may alter the course of some infections, change the way the body responds to vaccination, and may also have a role in some immune-related diseases such as multiple sclerosis. How it is that these wavelengths just beyond visible light can affect the immune system is the subject of this project. We know that UV radiation can penetrate only a short way into the skin, yet can have widespread effects on the immune system. Our research to now has shown that a particular cell type sitting just below the surface of skin, the dermal mast cell, is essential. We've also demonstrated some of the complexity of the early response to UV exposure - both a chemical (cis-urocanic acid) in the very outermost layer of skin, and nerves in the skin, have roles. Importantly, anti-histamines can inhibit UV effects on immune responses. Additional lines of evidence also point to histamine, a product of mast cells, as playing a pivotal role in the immune alterations following UV exposure. Our research aims to characterise the effects of histamine on cells central to the development of immune responses, known as dendritic cells, and define the mechanisms of the effect in experimental models. In collaboration with researchers in the UK, we will further characterise the role of mast cells in UV alterations to immunity in humans.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.
Cutaneous Inflammation, Bone Marrow Dendritic Cells, And Implications For Immune Responses And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$327,151.00
Summary
With inflammation of the skin due to excessive sun exposure or chemicals, biological signals are sent to the bone marrow where immune fighting cells are generated. However, the immune system must not overreact. We have measured bone marrow derived immune cells with reduced function following skin inflammation which we propose is part of homeostasis. We need to better understand how these cells are altered and for how long they are altered.
Molecular And Cellular Mechanisms Of Cytotoxic Lymphocyte Perforin
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Cytotoxic lymphocytes are immune cells, which recognise and kill virus-infected or cancer cells. Perforin is essential for the activity of cytotoxic lymphocytes. The loss of perforin function results in an inherited immune deficiency, or may lead to the development of cancer. Despite a key role of perforin, its mechanism of action and the regulation of activity are unknown. I propose to elucidate these aspects of perforin biology. This is important for understanding immune regulation in humans.