Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blo ....Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blocked with the ultimate goal to cure the disease. Using an experimental model of pernicious anaemia in mice, where the basic pathology is immune-mediated gastritis, the disease will be treated by presenting the disease causing autoantigen via modified, or immature, antigen presenting cells to the immune system. In other experimental models which form the background to this project we have shown that this approach leads to down-regulation of the immune response by generating cells which specifically suppress the immune system. In our studies of autoimmune gastritis we will obtain modified antigen presenting cells from the skin, the blood, the spleen and thymus and use these cells to define optimal conditions for presenting the auto-antigen molecules to achieve the ultimate goal, which is antigen specific suppression of autoimmune gastritis. Our hypothesis is that immature antigen presenting cells are unable to present antigen to induce an effective immune response, but instead induce a response that results in antigen specific suppression. We intend to use this antigen specific suppression to prevent the establishment of autoimmune gastritis as well as treatment of established disease. This is a unique and potentially valuable strategy to treat autoimmune gastritis and offers the potential to apply this approach to other autoimmune conditionsRead moreRead less
Pre-clinical Evaluation Of Nano-membrane Dressings To Promote Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$188,600.00
Summary
This project will investigate whether a novel type of wound dressing can promote faster wound healing and reduce scarring. Time taken to heal is one of the best predictors of whether a wound will heal with significant scarring. The faster wounds heal the better. We have identified a new dressing with specific nano-scale pores that may promote faster healing. This dressing will be tested in the best model of human wound healing with the potential to progress to clinical trials if successful.
This is a study of the senses which arise from our muscles and which tell us where our different body parts are, at any point in time. These senses, collectively called proprioception, are also involved in the automatic, unconscious control of our muscles. So, ultimately, they allow us to stand and to move freely with precision and confidence, even in the dark. One of these senses, the sense of effort or of heaviness, is believed to be generated within the brain. It intensifies when we become fa ....This is a study of the senses which arise from our muscles and which tell us where our different body parts are, at any point in time. These senses, collectively called proprioception, are also involved in the automatic, unconscious control of our muscles. So, ultimately, they allow us to stand and to move freely with precision and confidence, even in the dark. One of these senses, the sense of effort or of heaviness, is believed to be generated within the brain. It intensifies when we become fatigued. These experiments will be concerned with finding out more about how this works. We have a method that uses magnetic stimulation of the brain to change its control of our muscles. Using it we will learn how this sense is generated. When we close our eyes and move our limbs we realise that we know exactly where they are at any point in time. It remains uncertain exactly how this information is generated within the nervous system. One idea, arising from some recent experiments which we want to test, is that as we move the limb, the skin over the moving parts is stretched and stretch-sensitive nerve endings in the skin provide us with information about the movement. Alternatively, perhaps it is the effort we exert to maintain limb position against the force of gravity which tells us where the limb is. In another recent study we have found that when a muscle has become painful from excessive exercise or from some local strain injury, our ability to control the muscle and so move the limb is no longer as effective. We want to study the underlying nervous mechanisms responsible for the changes in movement control. Are they designed to spare the muscle while it recovers from injury? How are they brought about? All of this work is important for a better understanding of ourselves, for a better clinical diagnosis when something goes wrong and for improved treatment of diseased or injured muscles.Read moreRead less
Opioid Actions On Sensory Neuron Excitability In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$241,018.00
Summary
Morphine and related drugs are very widely used for pain relief, although the way they affect the pain-sensitive cells in the body is not well understood. Use of morphine for extended periods of time often makes morphine less effective for pain relief, which makes it necessary to increase the dose of morphine given. This leads to an increase in the unwanted side effects of morphine, and can eventually lead to morphine becoming ineffective in controlling pain. This study is designed to examine ho ....Morphine and related drugs are very widely used for pain relief, although the way they affect the pain-sensitive cells in the body is not well understood. Use of morphine for extended periods of time often makes morphine less effective for pain relief, which makes it necessary to increase the dose of morphine given. This leads to an increase in the unwanted side effects of morphine, and can eventually lead to morphine becoming ineffective in controlling pain. This study is designed to examine how morphine affects pain-sensitive cells, and to determine how continued use of morphine changes the way pain-sensitive cells respond to morphine. We hope that by understanding how morphine works on pain-sensitive cells, we can understand why it does not work so well after continued use. This information should enable us to design better forms of pain relief than we have now.Read moreRead less
Cellular And Molecular Events During Antigen Dependent B Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$283,329.00
Summary
The immune system is essential for protecting us against invasion from without by viruses and bacteria and invasion from within by cancer cells. Among the white blood cells making up this system are those responsible for producing antibodies. To ensure that all possible infections and tumours can be recognised, the body needs to manufacture a very large number of these cells on a continuous basis. The aim of this project is to work out the mechanism responsible for controlling their production a ....The immune system is essential for protecting us against invasion from without by viruses and bacteria and invasion from within by cancer cells. Among the white blood cells making up this system are those responsible for producing antibodies. To ensure that all possible infections and tumours can be recognised, the body needs to manufacture a very large number of these cells on a continuous basis. The aim of this project is to work out the mechanism responsible for controlling their production and function using a novel experimental system. By pinpointing the different stages involved in antibody production in the normal host we should be in a better position to make longer lasting vaccines in the future and to understand what goes wrong with these white cells in disease. In particular, the results should shed light on the chronic form of leukaemia called myeloma and some of the autoimmune disorders like the rheumatic diseases which occur when the antibodies being produced attack our own tissues.Read moreRead less
Adult non-Hodgkin?s lymphoma (NHL) is one of the most rapidly increasing cancers of recent times. The rise has occurred worldwide in men and women of all ages. The reason for most of the rise is unknown. It has recently been proposed that part of the upsurge may be due to increases in sun exposure which have occurred during the same period. There is some indirect evidence to support this hypothesis. For example, the rate of occurrence of NHL is higher closer to the equator in Australia than it i ....Adult non-Hodgkin?s lymphoma (NHL) is one of the most rapidly increasing cancers of recent times. The rise has occurred worldwide in men and women of all ages. The reason for most of the rise is unknown. It has recently been proposed that part of the upsurge may be due to increases in sun exposure which have occurred during the same period. There is some indirect evidence to support this hypothesis. For example, the rate of occurrence of NHL is higher closer to the equator in Australia than it is in England and Wales, and NHL is diagnosed more frequently among British migrants to Victoria than it is in their homeland. The sunlight hypothesis will be tested by comparing the pattern of sun exposure in Tasmanians diagnosed with NHL during the years 1998-2001 and in a sample of Tasmanians without the disease. tasmania has been chosen because levels of ultraviolet (UV) radiation are low there in all but the summer months, when it approaches the levels of Brisbane, Sydney and Melbourne. There is therefore a greater difference in UV exposure between the most exposed and the least exposed in Tasmania, making it an ideal location to test the hypothesis. The link between NHL and a measure of melanin pigmentation in the skin will also be studied. The incidence of NHL is higher in lighter-skinned ethnic groups than it is in darker-skinned people living at the same latitude, but it is not known whether risk varies within Caucasian populations. A new measure of melanin in the skin, developed at the Menzies Centre for Population Health Research in Hobart, will better allow the effects of skin colour to be studied.Read moreRead less